tbuckley/cabot-search huggingface dataset:
PDTM-36. WHOLE EXOME SEQUENCING (WES) OF DIPG PATIENTS FROM THE BIOMEDE TRIAL REVEALS NEW PROGNOSTIC SUBGROUPS WITH SPECIFIC ONCOGENIC PROGRAMMES
Authors: Marie-Anne Debily, Thomas Kergrohen, Pascale Varlet, Gwenael Le Teuff, Karsten Nysom, Klas Blomgren, Pierre Leblond, Anne-Isabelle Bertozzi, Emilie De Carli, Celine Chappé, Samia Ghermaoui, Emilie Barret, Stephanie Picot, Arnaud Tauziède-Espariat, Stephanie Puget, David Castel, Gilles Vassal, Jacques Grill
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND &amp; METHODS. The BIOlogical MEdicines for DIPG Eradication (BIOMEDE) trial is a randomized multi-arm multi-stage program (drop-the-loser adaptive design). The first trial was an open-label phase-II trial comparing three drugs (everolimus, dasatinib, erlotinib) combined with irradiation, allocated according to the presence of their specific targets. All patients underwent a biopsy at diagnosis to confirm the DIPG molecularly and establish the expression of pre-specified biomarkers. Patient samples were explored by WES with a sequencing depth average &gt;100X for the tumor and &gt;60X for the blood. RESULTS. Unsupervised clustering of copy-number-variations (CNV) identified 4 groups corresponding to a new stratification of DIPG: cluster 1 (n=42) with high CNV, cluster 2 (n=23) with chromosome 1q + chromosome 2 gains, cluster 3 (n=9) with low CNV and cluster 4 (n=21) with isolated 1q gain. Clusters 1 had higher hazard-ratio for death than the others (mean HR 1.959, range 1.054–3.643, p&lt; 0.0001, adjusted Cox model). Extensive structural rearrangements/chromotrypsis were significantly more frequent in TP53-mutated samples. Indeed, when stratiftying patients in 4 groups based on type of histone H3 mutated at K27 and the presence of a TP53 pathway alteration the subgroup with TP53 altered pathway had a significantly higher hazard-ratio for death than the others (mean HR 3.450, p=0.0017, adjusted Cox model). Additional drug targets were identified, especially in the DNA repair machinery that could be exploited for new targeted therapies. CONCLUSION. WES at diagnosis was feasible in most patients and brings new prognostic and theranostic informations. This allows a better patients stratification and the development of personalized medicine in DIPG.
PDTM-26. NOVEL SHARED AND DISTINCT EPIGENOMIC MECHANISMS OF G34R AND K27M MUTATIONS IN CHILDHOOD GLIOMA
Authors: Michael Chen, Kelly Bush, Nichole Lewis, Vanessa Cervantes, Paul Knoepfler
Journal: Neuro-Oncology (2019)

Abstract Alterations in histone H3.3 are common driver mutations in high-grade pediatric gliomas, but the central oncogenic mechanisms remain an open question. To identify important mutant H3.3 effectors, we used CRISPR-Cas9 to precisely introduce H3.3 K27M and G34R mutations into previously H3.3-wildtype human astrocyte and glioma cells, while in parallel reverting mutations in glioma cells back to wildtype. K27M and G34R mutations invoked some strikingly similar epigenomic effects supporting a new model in which some major aspects of their oncogenic functions are shared. For instance, both K27M and G34R induced changes at many of the same genomic loci in specific histone marks, with the largest changes in H3K27me3 including in particular within super-enhancers, which also exhibited perturbed transcriptional function. K27M and G34R mutations induced some gene expression changes that were unique to each mutation, but both mutations changed similar functional ontological clusters and ASCL1 is a shared key putative effector. H3.3 mutant glioma cells are sensitive to ASCL1 knockdown or overexpression, resulting in cell viability that is reduced or increased, respectively. Comparison of our panel of glioma cells gene-edited with precise point mutations to edited glioma cells in other studies that performed gene knockout or overexpression reveals striking differences in the resulting phenotypes. We also determined that certain drugs exhibited specificity to H3.3 mutation-bearing cells including DAPT, JQ1, and ONC201. In vivo, we found that reversion of K27M to WT in glioma cells significantly reduced tumorigenicity in mouse xenograft assays and introduction of G34R mutations in previously WT glioma cells increased tumor growth. Overall, gene editing of gliomas and comparison of otherwise isogenic sets of cells defines both distinct and shared gliomagenesis mechanisms that can be targeted for development of oncohistone-based therapeutics.
The Global State of Hematopoietic Stem Cell Transplantation for Multiple Myeloma: An Analysis of the Worldwide Network of Blood and Marrow Transplantation (WBMT) Database and the Global Burden of Disease Study
Authors: Andrew J. Cowan, Helen Baldomero, Yoshiko Atsuta, Joseph Mikhael, Mahmoud Aljurf, Adriana Seber, Hildegard T. Greinix, Mickey Koh, Nina Worel, Edward N. Libby, Marcelo C. Pasquini, Sebastian Galeano, Gregorio Jaimovich, Juliana Martinez Rolon, Yoshihisa Kodera, Malek Benakli, Bazuaye G Nosakhare, Alaa M. Elhaddad, Jeffrey Szer, Jakob R. Passweg, Nicolaus Kroeger, Daniel J. Weisdorf, Dietger Niederwieser
Journal: Blood (2019)
NPM1 mutations Using Deep Amplicon Sequencing and Broad Next Generation Sequencing at the Time of Complete Remission Is Informative to Predicting Risk of Relapse Following Intensive Chemotherapy
Authors: Bhavana Bhatnagar, Shelley Orwick, Nyla A. Heerema, Alison R. Walker, Alice S. Mims, James S. Blachly, Karilyn Larkin, Nicole Grieselhuber, Gregory K. Behbehani, Apollinaire Ngankeu, Charles Thomas Gregory, John C. Byrd
Journal: Blood (2019)
ACTR-29. A SERIES OF PATIENTS (PTS) WITH RECURRENT GBM (rGBM) TREATED WITH ABT-414, BEVACIZUMAB (BEV) AND CCNU
Authors: Madhawa De Silva, Adrian Lee, Marina Kastela, Helen Wheeler, Mustafa Khasraw
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND ABT-414 showed encouraging results in the phase 2 Intellance 2 rGBM study, but not in the phase 3 Intellance 1 trial, in newly diagnosed EGFR-amplified GBM. We describe a series of pts with rGBM treated with ABT-414 in combination with Bev and CCNU. METHODS A retrospective review of pts with rGBM receiving ABT-414 with Bev and CCNU. RESULTS Between 3 and 10/2018, 6 male pts (median age 54y) with EGFR-amplified rGBM were given 1 mg/kg ABT-414 every 3 - 5 weeks (wk) in combination with 10 mg/kg Bev fortnightly. Two pts also received CCNU. Two pts had multifocal disease, and the remainder had left parietal, left frontal, occipital, and right frontal GBMs. All pts were IDH wild-type, and 5 out of 6 were MGMT-unmethylated. Four pts had upfront resection followed by adjuvant therapy, and received between 1 and 8 lines of therapy prior to ABT-414. Median time from chemoradiotherapy to ABT-414 was 34 wk. At time of abstract submission, median duration of therapy was 30 wk (range 5 – 64). Three pts were still alive, 1 on ABT-414 plus Bev, 1 on Bev alone (after ABT-414 + Bev), and 1 on best supportive care. Three pts died after 5, 17, and 42 wk, respectively. All pts developed ocular toxicities, manageable with dose reduction or delays, but no other grade 3 or 4 toxicities. CONCLUSION ABT-414 with Bev and CCNU was tolerable in this selected small series of pts with EGFR-amplified rGBM, and may have potential activity in selected patients, with 4 out of 6 pts (three MGMT-unmethylated) achieving a PFS greater than 27 wk (range 27 – 64). Despite the outcome of Intellance 1, there may be a subgroup of relapsed pts who benefit from this combination. Further studies are warranted to identify and analyse this group.
Study of Seroprevalence of Hepatites "B" and "C" Markers in Blood Donors from Hemonorte, Rio Grande Do Norte/ Brazil
Authors: Ralfo Cavalcanti Medeiros, Manuel Josué Batista Neto, Aldair Sousa Paiva, Valéria SF Sales, Rodrigo Villar Freitas, Hugo Diogenes De Oliveira Paiva, Rafael Santiago Araujo, Geraldo Barroso Cavalcanti
Journal: Blood (2019)
Mechanical Ventilation. Physiological and Clinical Applications
Journal: Thorax (1986)

Part I: Basic Concepts and Core Knowledge in Mechanical Ventilation 1. Basic Terms and Concepts of Mechanical Ventilation 2. How Ventilators Work 3. How a Breath is delivered Part II: Initiating Ventilation 4. Establishing the Need for Mechanical Ventilation 5. Selecting the Ventilator and the Mode 6. Initial Ventilator Settings 7. Final Considerations in Ventilator Setup Part III: Monitoring in Mechanical Ventilation 8. Initial Patient Assessment 9. Ventilator Graphics 10. Assessment of Respiratory Function 11. Hemodynamic Monitoring Part IV: Therapeutic Interventions -- Making Appropriate Changes 12. Methods to Improve Ventilation in Patient-Ventilator Management 13. Improving Oxygenation and Management of ARDS Part V: Effects and Complications of Mechanical Ventilation 14. Ventilator-Associated Pneumonia NEW! 15. Sedatives, Analgesics, and Paralytics 16. Extrapulmonary Effects of Mechanical Ventilation 17. Effects of Positive Pressure Ventilation on the Pulmonary System 18. Troubleshooting and Problem Solving Part VI: Noninvasive Positive Pressure Ventilation 19. Basic Concepts of Noninvasive Positive Pressure Ventilation Part VII: Discontinuation from Ventilation and Long Term Ventilation 20. Discontinuation and Weaning from Mechanical Ventilation 21. Long Term Ventilation Part VIII: Neonatal and Pediatric Ventilation 22. Neonatal and Pediatric Ventilation NEW! Part IX: Special Techniques in Ventilatory Support 23. Special Techniques in Ventilation Appendices: A: Review of Abnormal Physiological Processes B: Graphics Exercises Glossary
MNGI-05. COMBINED MULTIMODAL TREATMENT REGIMEN IN RECURRENT MENINGIOMAS
Authors: Jose Carrillo, Naveed Wagle, Garni Barkhoudarian, Daniel Kelly, Annie Heng, Jaya Gill, Tiffany Juarez, Santosh Kesari
Journal: Neuro-Oncology (2019)

Abstract Meningiomas are the most common primary brain tumor, subsequent tumor progression can be problematic for surgical treatment options based upon location. Currently there is limited activity of various single agent medical therapies. We evaluated a combined treatment modality in recurrent Meningiomas. Patients were consented to NOC study protocol JWCI-17–0401 in this retrospective analysis. Treatment consisted of combination Octreotide LAR, Everolimus, Hydroxyurea, and Mifepristone. Patient characteristics in the combined treatment meningioma group (n=12) had a median age 60, 50% male, 47% WHO grade I, 37% WHO grade II, 11% WHO grade III, 67% skull base location, median number of recurrences is 2.2, with median number of surgeries of 1.7. Total comparison meningioma patients (n=19) with median age 62, 42% male, 42% WHO grade I, 50% WHO grade II, 17% WHO grade III, 58% skull base location, median number of recurrences is 2.2, with median number of surgeries of 2.2. Median PFS in recurrence prior to initiation of multimodal combined therapy, mPFS=283 days. Median PFS with subsequent multimodal combined therapy, mPFS=318 days. Multimodal therapy may prolong mPFS in recurrent meningiomas. Our pilot data supports further clinical trials in combined multimodal treatments.
Seroprevalence of Pre-Existing Nabs Against AAV1, 2, 5, 6 and 8 in South African Hemophilia B Patient Population
Authors: Anna Majowicz, Nolukholo Ncete, Floris van Waes, Nikki Timmer, Sander J van Deventer, Johnny N Mahlangu, Valerie Ferreira
Journal: Blood (2019)
Aberrant Cathepsin S Induces a Supportive Immune Microenvironment in Follicular Lymphoma
Authors: Johannes Adrian Hildebrand, Deepak Bararia, Sebastian Stolz, Sarah Haebe, Stefan Alig, Michael Bartoschek, Michael Boesl, Alessandro Pastore, Erik Gaitzsch, Michael Heide, Vindi Jurinovic, Monika Szczepanowski, Wolfram Klapper, Abner Louissaint, Christina Ludwig, Sebastian Bultmann, Heinrich Leonhardt, Sebastian Eustermann, Karl-Peter Hopfner, Wolfgang Hiddemann, Michael von Bergwelt, Christian Steidl, Robert Kridel, David M Weinstock, Marc Schmidt-Supprian, Menyhárt B Sárosi, Verena Passerini, Josef Mautner, Oliver Weigert
Journal: Blood (2019)
CMET-34. IMPROVEMENT OF LEPTOMENINGEAL DISEASE FOLLOWING INFECTIOUS MENINGITIS
Authors: Nicholas Metrus, Carolos Kamiya, Shiao-Pei Weathers, Christa Seligman, Barbara O’Brien
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION The incidence of leptomeningeal disease (LMD) is increasing, due to better imaging, earlier diagnosis and improved systemic disease control. However, many of the systemic therapies do not cross the blood brain barrier (BBB) and, despite treatment with radiation and/or intrathecal (IT) chemotherapy, median survival is approximately 4-6months in solid tumors complicated by LMD. Repeated IT injections increase the risk of CNS infection. Preclinical models have shown that infectious meningitis transiently modifies the BBB. METHODS Our series consisted of 6 LMD patients (5 breast cancer primary, 1 lung cancer primary) treated on IT chemotherapy at MD Anderson Cancer Center between 2013 and 2018, who subsequently developed infectious meningitis. Three patients had history of parenchymal metastases in addition to LMD and four had history of radiation to brain and/or spine. LMD was confirmed by cytology and/or imaging. All were treated with IT topotecan. RESULTS CSF cultures were positive for Proprionobacterium acnes in three patients, Pseudomonas aeruginosa in two, and Raoultella ornithinolytica in one, who died shortly thereafter. Antibiotic regimens were variable. Three patients went on to receive IT chemotherapy post-infection (two never discontinued IT chemotherapy throughout infection). Those that had IT chemotherapy post-infection cleared CSF and imaging findings of LMD or maintained stability of radiographic LMD burden until death. No patients died directly from LMD. One patient, who developed infection after Ommaya placement and was never initiated on IT chemotherapy, still cleared his CSF of malignant cells. Excluding the patient who died shortly after meningitis diagnosis, the average time from meningitis diagnosis to death was 8.8 months and the average median survival from LMD diagnosis to death was 14 months. CONCLUSION Our findings support further evaluating the safety and timing of IT chemotherapy with active infectious meningitis and the potential synergistic benefit of increased immunogenicity and chemotherapy in LMD.
Modulation of pancreatic cancer cell sensitivity to FOLFIRINOX through microRNA-mediated regulation of response to DNA damage
Authors: A. Lampis, P. Carotenuto, S. Hedayat, M.C. Previdi, D. Zito, F. Sclafani, C. Parisi, J.C. Hahne, A. Hallsworth, V. Kirkin, K. Young, K. Kouvelakis, S.X. Azevedo, M. Vasiliki, A. Scarpa, D. Cunningham, I. Chau, N. Valeri, M. Fassan, C. Braconi
Journal: Annals of Oncology (2019)
Selection of Pru p 3 hypoallergenic peach and nectarine varieties
Authors: Jing Jin, Ling Gao, Lan Zhao, Zhong‐shan Gao, Xiong‐wei Li, Han‐bing Xie, Jun‐bei Ni, Ke‐xin Gan, Shan‐dong Wu, Zheng‐wen Ye, Jun Luo, Ke Cao, Rui‐juan Ma, Miao‐jin Chen, Pere Arús, Serge A. Versteeg, Hui‐ying Wang, Mei-ling Liu, Hui‐juan Jia, Ronald van Ree
Journal: Allergy (2019)

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Early Response Observed in Pediatric Patients with Refractory/Relapsed B-Cell Non-Hodgkin Lymphoma Treated with Sequential Chimeric Antigen Receptor T Cells
Authors: Wenqun Zhang, Bo Hu, Ling Jing, Jing Yang, Shan Wang, Yang Liu, Juan Du, Yaoliang Ren, Yonghong Zhang
Journal: Blood (2019)
EXTH-52. CO-TARGETING ONCOSTATIN M RECEPTOR USING MONOCLONAL ANTIBODIES IN COMBINATION WITH PRESENT STANDARDS OF CARE FOR GLIOBLASTOMA
Authors: Audrey Burban, Ahmad Sharanek, Arezu Jahani-Asl
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma Multiform (GBM) is the most aggressive primary tumor in the adult brain. The present standard of care includes surgical removal of the tumors followed by treatment with Temozolomide (TMZ) and radiation therapy. Despite intense efforts and advances in surgery and combination therapy, the median survival rate for GB patients remain 16 months following diagnosis. EGFRvIII/STAT3 signaling plays critical roles in GBM pathogenesis. We have recently discovered that the tumorigenic capacity of EGFRvIll/STAT3 pathway crucially depends on the cytokine receptor for Oncostatin M (OSMR). OSMR is a required co-receptor of EGFRvIII and a direct transcriptional target of STAT3. Strikingly, OSMR is highly expressed in brain tumor stem cells (BTSCs), a population of self-renewing malignant stem cells within GBM that contribute to tumor growth, recurrence and therapeutic resistance. We have generated therapeutic monoclonal antibodies against OSMR (OSMR mAb) that function as powerful inhibitors of OSMR. Treatment of BTSCs with OSMR mAb resulted in inhibition of OSMR-mediated signaling pathways and significantly impaired the phosphorylation of STAT3. Strikingly, treatment of BTSCs with OSMR mAb significantly attenuated BTSC self-renewal in limiting dilution assay and sensitized their response to tyrosine kinase inhibitors (TKI), ionizing radiation and TMZ. Using patient derived stem cell tumor xenografts, we have shown that OSMR mAb significantly reduced tumor growth compared to IgG control. Together, our findings suggest that targeting OSMR using therapeutic monoclonal antibodies in combination with EGFR inhibitors and/ or the current standard of care may provide a promising therapeutic strategy for glioblastoma.
Pulmonary alveolar microlithiasis
Authors: M. R. Sears, A. R. Chang, A. J. Taylor
Journal: Thorax (1971)

Pulmonary alveolar microlithiasis is a rare condition of unknown aetiology which is emerging from obscurity and being more frequently recognized. The case histories of two patients, one of whom is the oldest reported case in the literature, are described. In one case extensive fibrosis of interstitial tissue was present and many calcospherites appeared to lie outside the alveolar spaces. Calcospherites were also found in the bronchial wall of this patient, and this has not previously been reported. The lungs were analysed for calcium, phosphate, and iron, and detailed respiratory function tests were done in one patient; all results were similar to those previously reported in this condition.
Socio-economic factors and outcomes in heart failure: Insights from the ASIAN-HF registry
Authors: W. T. Tay, T. H. K. Teng, J. Tromp, J. J. L. Yap, M. R. Macdonald, C. Chandramouli, E. Geelhoed, A. M. Richards, I. S. Anand, C. S. P. Lam
Journal: European Journal of Heart Failure (2018)
A Multicenter Nonrandom Clinical Study Using Induction Regimen of FLAG-IDA or Dae in Treatment of 101 Children with Newly Diagnosed CBF-AML in South of China: Clinical Responses and the Midterm Report of Survival
Authors: Xiaoqin Feng, Jian Li, Chunfu Li, Mincui Zheng, Honggui Xu, Yingyi He, Changgang Li, Hong Wen, Xiangling He, Lihua Yang
Journal: Blood (2019)
TMOD-08. SERUM ESTABLISHED CANCER STEM CELL CULTURES REPRESENT UNIQUE MODELS OF GLIOBLASTOMA INTER-TUMOR HETEROGENEITY
Authors: Nagaprathyusha Maturi, E-Jean Tan, Yuan Xie, Anders Sundström, Tobias Bergström, Olivera Casar-Borota, Yiwen Jiang, Lene Uhrbom
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma (GBM) is the most frequent primary malignant brain tumor. The invasive and heterogeneous nature of GBM stem cells (GSCs) provide the basis for extreme therapy resistance of GBM and the majority of patients survive less than one year from diagnosis. Relevant models of GBM are important for basic research and drug screening and development, and the current consensus in the field is that GSCs are most faithfully maintained under serum-free neural stem cell (NSC) conditions. We have used serum-free NSC media to explant 230 patient-derived GBM samples, and have in parallel also explanted the same samples in regular serum-containing media. We found, accordingly, that serum-free media was most effective in generating sustainable cultures (137/230, 60%), called serum-free (SF) cultures. Interestingly, we also found that that there was a subgroup of GBM specimens that could only be established in serum-containing media (31/230, 13%), called exclusive serum-containing (eSC) cultures. We characterized a number of the eSC cultures and found that they expressed typical GSC markers such as MSI-1, BMI-1, nestin, CD44 and SOX2. They also displayed all functional characteristics of GSCs, i.e. extended proliferation, sustained self-renewal and orthotopic tumor initiation. Molecular analyses showed that the eSC cultures were most closely related to but separated from mesenchymal subtype GBM. In summary we have established GSC cultures that would have evaded modeling under serum-free conditions, representing unique cell models of GBM inter-tumor heterogeneity. Key words: Glioblastoma, serum cultures, stem-like cells, GBM heterogeneity
Performance of the New Automated Latex Immunoturbidometric Assay in the Diagnosis of Heparin Induced Thrombocytopenia: A Single Institution Experience
Authors: Sriman Swarup, Somedeb Ball, Nimesh Adhikari, Anita Sultan, Khatrina Swarup, Kyaw Zin Thein, Miguel Quirch, Lukman Tijani, Sanjay Awasthi
Journal: Blood (2019)
Lenalidomide Induction and Maintenance Maximizes Outcome for Newly Diagnosed Transplant Eligible Myeloma Patients Irrespective of Risk Status: Long-Term Follow-up of the Myeloma XI Trial
Authors: Graham Jackson, Charlotte Pawlyn, David Cairns, John R Jones, Bhuvan Kishore, Mamta Garg, Cathy Williams, Kamaraj Karunanithi, Jindriska Lindsay, Nigel H. Russell, Matthew Jenner, Gordon Cook, Mark T Drayson, Roger G. Owen, Walter M Gregory, Martin F. Kaiser, Faith E. Davies, Gareth Morgan
Journal: Blood (2019)
High Mobility Group A1 Chromatin Regulators: Key Epigenetic Switches and Therapeutic Targets Required for Leukemic Transformation in JAK2 Mutant MPN
Authors: Liping Li, Wenyan Lu, Alison R. Moliterno, Lingling Xian, Joseph Kim, Ophelia Rogers, Jerry L. Spivak, Linda Resar
Journal: Blood (2019)
Incidence of Hypersensitivity Reactions (HSR) Reactions (HSR) to Peg-Asparaginase (PEG-ASP) in 6136 Patients Treated in the AIEOP-BFM ALL 2009 Study Protocol
Authors: Carmelo Rizzari, Anja Moericke, Valentino Conter, Maria Grazia Valsecchi, Martin Zimmermann, Daniela Silvestri, Georg Mann, Felix Niggli, Luciano Dalla-Pozza, Jan Stary, Sarah Elitzur, Gunnar Cario, Franco Locatelli, Joachim Boos, Massimo Zucchetti, Andrea Biondi, Martin Schrappe
Journal: Blood (2019)
Improved Gvhd Free, Relapse Free Survival Using Dual T-Cell Depletion with ATG and Ptcy in Matched Unrelated Donor RIC Allo-HSCT
Authors: Maria Queralt Salas, Wilson Lam, Arjun Law, Fotios V. Michelis, Dennis Dong Hwan Kim, Zeyad Al-Shaibani, David Loach, Jeffrey H. Lipton, Rajat Kumar, Jonas Mattsson, Auro Viswabandya
Journal: Blood (2019)