tbuckley/cabot-search huggingface dataset:
EXTH-37. A NOVEL TRANSDUCER ARRAY LAYOUT FOR DELIVERING TUMOR TREATING FIELDS TO THE SPINE
Authors: Ariel Naveh, Ofir Yesharim, Ze’ev Bomzon
Journal: Neuro-Oncology (2019)

Abstract Tumor Treating Fields (TTFields) are an antimitotic technology utilising electric fields to disrupt mitosis in cancer cells. TTFields are currently approved by the FDA for the treatment of Glioblastoma Multiforme (GBM) and Malignant Pleural Mesothelioma (MPM). TTFields are delivered through 2 pairs of transducer arrays placed on the patient’s skin. Each pair delivers TTFields in a single direction, and the pairs are placed to provide perpendicular field. Preclinical studies show that 1V/cm is the clinical threshold for the treatment to be effective. Some types of cancers send metastases to the spinal cord and CSF, i.e. leptomeningeal disease. The purpose of this study was to find transducer array layouts that deliver TTFields to the spine at therapeutic intensities of above 1 V/cm. Computational simulations testing the delivery of TTFields to the spine were performed using the Sim4Life 4.0 (ZMT Zurich) computational platform, and the Duke 3.1 and Ella 3.0 (ITI’S, Zurich) realistic computational models of a male and female respectively. “Standard” layouts in which a pair of arrays are placed on the front and back of the patient and second pair on the lateral aspects of the patient failed to deliver TTFields at therapeutic intensities to the spinal cord. This is probably because the spinal cord is surrounded by the CSF and spine, which shunt the electric fields from reaching the spinal cord. However, field intensities above 1 V/cm were observed when delivering TTFields when both arrays were placed on the patients back, with a first array placed close to the neck, and second array placed towards the thighs. In this case, the spinal cord and surrounding CSF act as a conductive cable, directing the electric field along the spine. This novel layout opens the possibility for treating cancerous disease along the spine.
Landscape of TP53 Mutations in MPN
Authors: Noushin Farnoud, Christopher Famulare, Elli Papaemmanuil, Erin McGovern, Juan Medina, Juan E. Arango Ossa, Raajit K. Rampal, Bing Li, Ross L. Levine, John Mascarenhas, Rona Singer Weinberg, Minal A Patel, Ronald Hoffman
Journal: Blood (2019)
EXTH-38. ENGINEERED EXOSOMES FOR THERAPEUTIC GENE DELIVERY IN BRAIN TUMORS
Authors: Malcolm McDonald, Irtiza Hasan, Satoshi Adachi, Joy Gumin, Daniel Ledbetter, Marc Daou, Sricharan Gopakumar, Eric Momin, Lihong Long, Lynette Phillips, Brittany Parker-Kerrigan, Anwar Hossain, Frederick Lang
Journal: Neuro-Oncology (2019)

Abstract The poor outcome of patients with glioblastoma (GBM) is at least partly due to the inability to deliver therapeutic agents to the tumor. We have shown that exosomes, naturally occurring nano-size extracellular vesicles, are capable of delivering antiglioma microRNAs (MiRs) to brain tumors (Lang, FM et al. Neuro Oncol, 2018;20(3):380–390). However, our studies suggested that there is significant opportunity to increase packaging efficiency and delivery specificity of exosomes. To this end, we engineered exosomes to express specific viral proteins (called eExos) in order to enhance packaging and delivery capabilities of antiglioma genes. These eExos are created by transfecting HEK 293 cells with plasmids containing viral proteins and a plasmid of the therapeutic gene. After 72 hrs, differential ultracentrifugation was used to isolate the exosomes. To test the efficacy of these novel eExos, we transfected them with a plasmid containing Cre recombinase (as the therapeutic gene), and treated U87 cells harboring a dsRed/eGFP Cre recombinase/LoxP site (U87dsR/GFP). In in vitro studies, treatment of U87dsR/GFP with a single dose of eExos resulted in 82% conversion rate of cells from red to green, compared to control exosomes (&lt; 18% green cells). In in vivo studies, a single intratumoral injection of eExos into mice harboring 7-day old intracranial U87dsR/GFP gliomas, resulted in significant increases in green cells compared to control exosomes when tumors were harvested at day 10. Mechanistic studies employing florescent microscopy demonstrate that in contrast to natural exosomes, eExos deliver their cargo to the nucleus rather than to lysosomes, avoiding degradation of the delivered agent and facilitating expression of the plasmid. We conclude that eExos, engineered to contain specific viral proteins, are capable of packaging and delivering antiglioma genes more effectively than natural exosomes and may overcome the current inability to deliver biological therapeutic agents to brain tumors.
Efficacy of Pomalidomide, Bortezomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma Post-Lenalidomide: Results from a Systematic Literature Review and Indirect Treatment Comparison
Authors: Katja C. Weisel, Sujith Dhanasiri, Aline Gauthier, Amie Padhiar, Eva Casal, Paul G. Richardson
Journal: Blood (2019)
Paradoxical clade- and age-specific vaccine effectiveness during the 2018/19 influenza A(H3N2) epidemic in Canada: potential imprint-regulated effect of vaccine (I-REV)
Authors: Danuta M Skowronski, Suzana Sabaiduc, Siobhan Leir, Caren Rose, Macy Zou, Michelle Murti, James A Dickinson, Romy Olsha, Jonathan B Gubbay, Matthew A Croxen, Hugues Charest, Nathalie Bastien, Yan Li, Agatha Jassem, Mel Krajden, Gaston De Serres
Journal: Eurosurveillance (2019)

IntroductionThe Canadian Sentinel Practitioner Surveillance Network reports vaccine effectiveness (VE) for the 2018/19 influenza A(H3N2) epidemic.AimTo explain a paradoxical signal of increased clade 3C.3a risk among 35-54-year-old vaccinees, we hypothesise childhood immunological imprinting and a cohort effect following the 1968 influenza A(H3N2) pandemic.MethodsWe assessed VE by test-negative design for influenza A(H3N2) overall and for co-circulating clades 3C.2a1b and 3C.3a. VE variation by age in 2018/19 was compared with amino acid variation in the haemagglutinin glycoprotein by year since 1968.ResultsInfluenza A(H3N2) VE was 17% (95% CI: -13 to 39) overall: 27% (95% CI: -7 to 50) for 3C.2a1b and -32% (95% CI: -119 to 21) for 3C.3a. Among 20-64-year-olds, VE was -7% (95% CI: -56 to 26): 6% (95% CI: -49 to 41) for 3C.2a1b and -96% (95% CI: -277 to -2) for 3C.3a. Clade 3C.3a VE showed a pronounced negative dip among 35-54-year-olds in whom the odds of medically attended illness were > 4-fold increased for vaccinated vs unvaccinated participants (p < 0.005). This age group was primed in childhood to influenza A(H3N2) viruses that for two decades following the 1968 pandemic bore a serine at haemagglutinin position 159, in common with contemporary 3C.3a viruses but mismatched to 3C.2a vaccine strains instead bearing tyrosine.DiscussionImprinting by the first childhood influenza infection is known to confer long-lasting immunity focused toward priming epitopes. Our findings suggest vaccine mismatch may negatively interact with imprinted immunity. The immunological mechanisms for imprint-regulated effect of vaccine (I-REV) warrant investigation.
Integrating Geriatric Assessment and Genetic Profiling to Personalize Therapy Selection in Older Adults with Acute Myeloid Leukemia (AML)
Authors: Vijaya R. Bhatt, Christopher Wichman, Zaid S. Al-Kadhimi, Thuy T. Koll, Ann Berger, James O. Armitage, Sarah A. Holstein, Krishna Gundabolu, Lori J. Maness
Journal: Blood (2019)
In-Hospital Outcomes in Elderly Acute Myeloid Leukemia (AML) Receiving Aggressive Inpatient Care: An Analysis of National Inpatient Sample (NIS) Database between Years 2005 and 2014
Authors: Sindhu Malapati, Sunny R K Singh, Rohit Kumar, Jibran Ahmed, Ishaan Vohra, Vatsala Katiyar
Journal: Blood (2019)
A novel endoscopic treatment for giant gastric bezoars: guidewire-based seesaw-type fragmentation using a specific bezoaratom kit
Authors: Xiao Hu, Ren-yi Zhang, Wei-hui Liu
Journal: Endoscopy (2019)

Although gastrointestinal endoscopy is the routine treatment for small gastric bezoars [1], management of massive bezoars is always difficult even with a specific lithotriptor [2], electrohydraulic lithotripsy [3] or laser fragmentation [4]. At present, surgery is the remedy treatment for such massive bezoars. However, contamination of the peritoneal cavity and remnant bezoars are major problems in surgical treatment [5]. To solve these problems, we established a novel endoscopic guidewire-based seesaw-type lithotripsy of massive gastric bezoars using a specific bezoaratom kit ([Fig. 1], [Video 1]).
CBMT-15. MET INHIBITION DRIVES PGC1A DEPENDENT METABOLIC REPROGRAMMING AND ELICITS UNIQUE METABOLIC VULNERABILITIES IN GLIOBLASTOMA
Authors: Yiru Zhang, Trang Nguyen, Junfei Zhao, Enyuan Shang, Consuelo Torrini, Peter D Canoll, Georg Karpel-Massler, Markus Siegelin
Journal: Neuro-Oncology (2019)

Abstract The receptor kinase, c-MET, has emerged as a target for glioblastoma therapy. However, treatment resistance evolves inevitably. By performing a global metabolite screen with metabolite set enrichment coupled with transcriptome and gene set enrichment analysis and proteomic screening, we have identified substantial reprogramming of tumor metabolism, involving oxidative phosphorylation and fatty acid oxidation (FAO) with a substantial accumulation of acyl-carnitines accompanied by an increase of PGC1a in response to genetic (shRNA and CRISPR/Cas9) and pharmacological (crizotinib) inhibition of c-MET. Extracellular flux and carbon tracing analyses (U-13C-Glucose and U-13C-Glutamine) demonstrated enhanced oxidative metabolism, which was driven by FAO and supported by increased anaplerosis of glucose carbons. These findings were observed in concert with increased number and fusion of mitochondria and production of reactive oxygen species (ROS). Genetic interference with PGC1a rescued this oxidative phenotype driven by c-MET inhibition. Silencing and chromatin immunoprecipitation experiments demonstrated that CREB regulates the expression of PGC1a in the context of c-MET inhibition. Interference with both oxidative phosphorylation (metformin, oligomycin) and beta-oxidation of fatty acids (etomoxir) enhanced the anti-tumor efficacy of c-MET inhibition. Moreover, based on a high-throughput drug screen, we show that gamitrinib along with c-MET inhibition results in synergistic cell death. Finally, utilizing patient-derived xenograft models, we provide evidence that the combination treatments (crizotinib+etomoxir and crizotinib+gamitrinib) were significantly more efficacious than single treatment without induction of toxicity. Collectively, we have unraveled the mechanistic underpinnings of c-MET inhibitor treatment and identified novel combination therapies that may enhance the therapeutic efficacy of c-MET inhibition.
Updated Preliminary Results from a Phase II Study Combining Azacitidine and Pembrolizumab in Patients with Higher-Risk Myelodysplastic Syndrome
Authors: Kelly S. Chien, Gautam M. Borthakur, Kiran Naqvi, Naval G. Daver, Jorge E. Cortes, Courtney D. DiNardo, Elias Jabbour, Michael Andreeff, Yesid Alvarado, Prithviraj Bose, Nitin Jain, Kimberly Sheppard, Cheri Klingner-Winton, Sherry A. Pierce, Xiao Qin Dong, Kelly Soltysiak, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2019)
Impact of Clinical Features, Cytogenetics, Genetic Mutations and Methylation of CDKN2B and DLC-1 Promoters on Treatment Response to Azacitidine
Authors: Iván Martín, Alicia Serrano, Blanca Navarro, Eva Villamón, Marisa Calabuig, Juan Carlos Hernandez Boluda, Javier F Chaves, María Isabel Orts, Nuria Yagüe, Paula Amat, Fernando Domingo, Yoana Hernández, Paula Coll, Azahara Fuentes, Enrique Seda, Francisca García, Angeles Muñoz, Carlos Solano, Mar Tormo
Journal: Blood (2019)
Outcomes of Ibrutinib (Ibr) Therapy in Ibr-Naïve Patients (pts) with Chronic Lymphocytic Leukemia (CLL) Progressing after Venetoclax (Ven)
Authors: Jennifer R. Brown, Matthew S. Davids, Julie E Chang, Shuo Ma, Juliana M L Biondo, Yong Mun, Madlaina Breuleux, William G. Wierda
Journal: Blood (2019)
Long-Term Outcome of Total Therapy Regimens: Impact of Molecular Subgroups
Authors: Frits van Rhee, Maurizio Zangari, Carolina D. Schinke, Guido J. Tricot, Doug Steward, Susan Panozzo, Jeffery R. Sawyer, Brian A Walker, Joshua Epstein, Faith E. Davies, Gareth Morgan, Adam Rosenthal, Antje Hoering, Katherine K Nishimura, Bart Barlogie
Journal: Blood (2019)
Alterations in Secretome and Transcriptome of Bone Marrow Derived MSCs in Patients with Diffuse Large B-Cell Lymphoma without Bone Marrow Involvement
Authors: Nataliya A. Petinati, Natalia Sats, Nina J. Drize, Irina Malyants, Victoria Shender, Ksenia Anufrieva, Polina Shneider, Tatiana Grigorieva, Georgiy Arapidi, Maria Lagarkova, Ekaterina A. Fastova, Aminat A. Magomedova, Sergey K. Kravchenko, Valeriy G. Savchenko
Journal: Blood (2019)
SURG-34. CLINICAL PREDICTORS OF TUMOR RECURRENCE AFTER PITUITARY ADENOMA RESECTION
Authors: Christina Jackson, Chau Vo, Marcus Daniels, Kaisorn Chaichana
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Repeat surgery after tumor recurrence after pituitary adenoma resection can be challenging due to formation of scar tissue and loss of surgical landmarks, which can lead to increased rates of postoperative complications. Identification of clinical predictors of tumor recurrence would allow for appropriate stratification of patients to optimize preoperative counseling and postoperative management. METHODS We conducted a retrospective review of 349 patients who underwent pituitary adenoma resection at Johns Hopkins Hospital between 2003 and 2017. We used unadjusted and adjusted logistic regression to identify predictors of tumor recurrence. Factors which were associated with tumor recurrence in univariable models (p&lt; 0.1), were included in our multivariable model. Factors that remained significantly associated with tumor recurrence (p&lt; 0.05) in our multivariable model were considered predictors of recurrence. RESULTS 59 (16.9%) patients developed tumor recurrence at the time of our study. Patients who had surgery through one nare, transcranial surgery, visual field deficit, larger tumor volume, bilateral cavernous sinus invasion, carotid artery invasion, and postoperative cerebral spinal fluid (CSF) leak were more likely to have tumor recurrence. Conversely, patients who are younger in age, had sphenoid packing, and gross total resection were less likely to have tumor recurrence. In our multivariable model, only age (adjusted odds ratio[aOR]: 0.96), surgery through one nare (aOR: 2.05), gross total resection(aOR: 0.21), and presence of CSF leak(aOR: 4.43) remained significantly associated with tumor recurrence. CONCLUSIONS We identified several predictors of tumor recurrence after pituitary adenoma resection. Notably, having gross total resection of the primary tumor had the most significant protective effect on tumor recurrence. Given the increased complication associated with repeat surgery, gross total resection should be attempted in all patients, if feasible. Patients with other predictors of tumor recurrence should be monitored more frequently to allow for early detection of recurrence to optimize treatment strategies.
Updated Meta-Analysis of Randomized Controlled Trials to Evaluate the Incidence of Infection and Pneumonia in Patients with Multiple Myeloma Treated with Daratumumab
Authors: Thura Win Htut, Aung M Tun, Anita Sultan, Myint Aung Win, Sriman Swarup, Ei Moe Phyu, Pwint Phyu Hlaing, Myat Min Han, Yin Mon Myat, Fred Hardwicke, Donald P. Quick, Nicholas D'Cunha, Lukman Tijani, Kyaw Zin Thein
Journal: Blood (2019)
The Possibilities of Diffusion-Weighted Magnetic Resonance Imaging in Determining the Burden of a Tumor in Patients with Follicular Lymphoma
Authors: Ekaterina S Nesterova, Galina A Yatsyk, Natalia S Lutsik, Sergey K. Kravchenko, Eduard G Gemdzhian, Valery G. Savchenko
Journal: Blood (2019)
The Ribosomal Biogenesis Inhibitor CX-5461 Is an Anti-Cancer Therapeutic That Increases Platelet Count in Mice and in Humans
Authors: Amandeep Kaur, Katherine M Hannan, Samina Nazir, Kylee H Maclachlan, Gretchen Poortinga, Si Ming Man, Simon Harrison, Ross D Hannan, Elizabeth E. Gardiner
Journal: Blood (2019)
Next Generation CRISPR Gene-Edited and Off-the-Shelf Virus-Specific T-Cells for the Immunocompromised Patient
Authors: Rafet Basar, May Daher, Nadima Uprety, Elif Gokdemir, Abdullah Saleh Alsuliman, Mayela Carolina Mendt, Lucila Kerbauy, Mayra Shanley, Gonca Ozcan, Emily Ensley, Ana Karen Nunez Cortes, Li Li, Junjun Lu, Mecit Kaplan, Vandana Nandivada, Mustafa Bdaiwi, Ye Li, Luciana Melo Garcia, Enli Liu, Sonny Ang, Pinaki P Banerjee, Richard E. Champlin, Elizabeth J. Shpall, Katayoun Rezvani
Journal: Blood (2019)
Treatment of Tetanus
Authors: N. D. Henderson
Journal: JAMA (1961)

<h3>To the Editor:—</h3> In the Aug. 6, 1960, issue ofThe Journal, Perlstein and associates discussed the routine treatment of tetanus. Under the heading "Tetanus Antitoxin and Toxoid," reference is made to the desensitization of the patient who has a positive intradermal sensitivity test. The recommendation is made to give the patient a series of injections of increasing concentratons at 15-minute intervals until "desensitization has been attained." After indicating the need for further research on sensitivity-testing procedures, Coca (<i>Asthma and Hay Fever in Theory and Practice</i>, pt. 1, Springfield, Ill.: Charles C Thomas, Publisher, 1931) commented as follows. If the presence of atopic hypersensitiveness to serum has been established, and if the individual's condition indicates the administration of a therapeutic horse serum, it is generally thought proper to employ the procedure of "desensitization" with the idea of establishing, within a short time, a tolerance sufficient for the administration of the therapeutic dose. The establishment of an increased tolerance in atopy usually requires a period of a number of weeks
NCF1-339 polymorphism is associated with altered formation of neutrophil extracellular traps, high serum interferon activity and antiphospholipid syndrome in systemic lupus erythematosus
Authors: Petrus Linge, Sabine Arve, Lina M Olsson, Dag Leonard, Christopher Sjöwall, Martina Frodlund, Iva Gunnarsson, Elisabet Svenungsson, Helena Tydén, Andreas Jönsen, Robin Kahn, Åsa Johansson, Lars Rönnblom, Rikard Holmdahl, Anders Bengtsson
Journal: Annals of the Rheumatic Diseases (2019)

​OBJECTIVES: A single nucleotide polymorphism in the NCF1 gene (NCF1-339, rs201802880), encoding NADPH oxidase type II subunit NCF1/p47phox, reducing production of reactive oxygen species (ROS) is strongly associated with the development of systemic lupus erythematosus (SLE). This study aimed at characterising NCF1-339 effects on neutrophil extracellular trap (NET) formation, type I interferon activity and antibody profile in patients with SLE. ​METHODS: Neutrophil NET-release pathways (n=31), serum interferon (n=141) and finally antibody profiles (n=305) were investigated in SLE subjects from Lund, genotyped for NCF1-339. Then, 1087 SLE subjects from the rheumatology departments of four Swedish SLE centres, genotyped for NCF1-339, were clinically characterised to validate these findings. ​RESULTS: Compared with patients with normal-ROS NCF1-339 genotypes, neutrophils from patients with SLE with low-ROS NCF1-339 genotypes displayed impaired NET formation (p<0.01) and increased dependence on mitochondrial ROS (p<0.05). Low-ROS patients also had increased frequency of high serum interferon activity (80% vs 21.4%, p<0.05) and positivity for anti-β2 glycoprotein I (p<0.01) and anticardiolipin antibodies (p<0.05) but were not associated with other antibodies. We confirmed an over-representation of having any antiphospholipid antibody, OR 1.40 (95% CI 1.01 to 1.95), anti-β2 glycoprotein I, OR 1.82 (95% CI 1.02 to 3.24) and the antiphospholipid syndrome (APS), OR 1.74 (95% CI 1.19 to 2.55) in all four cohorts (n=1087). ​CONCLUSIONS: The NCF1-339 SNP mediated decreased NADPH oxidase function, is associated with high interferon activity and impaired formation of NETs in SLE, allowing dependence on mitochondrial ROS. Unexpectedly, we revealed a striking connection between the ROS deficient NCF1-339 genotypes and the presence of phospholipid antibodies and APS.
The Vasculopathy in the Bone Marrow Microenvironment of Humanized Sickle Cell Mice Is Reversible By Blood Transfusion
Authors: Shin-Young Park, Alessandro Mattè, Yookyung Jung, Jina Ryu, Wilson Anand, Eun Young Anna Han, Min Liu, Carmine Carbone, Davide Melisi, Takashi Nagasawa, Charles Lin, Leslie E. Silberstein, Lucia De Franceschi
Journal: Blood (2019)
NIMG-17. CLINICOPATHOLOGIC AND ULTRASOUND VARIABLES ASSOCIATED WITH THE UNFAVORABLE PATHOLOGY IN NEUROBLASTOMA
Authors: Peixuan Sun, Yuyang Tong, Jun Du
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The International Neuroblastoma Pathology Classification has a prognostic impact that distinguishes two neuroblastoma categories: favorable histology (FH) and unfavorable histology (UFH). The aim of this study was to identify the clinicopathological and ultrasound variables that were associated with the UFH. METHODS With ethic approval, the clinical, pathologic, and ultrasonographic data of the 104 patients with the pathologic diagnosis of neuroblastoma were retrospectively analyzed. Pathologic findings were ascertained by the paraffin pathologic, fluorescent in situ hybridization (FISH), and the immunohistochemical stain analysis. Tumors were assessed for the following ultrasonographic characteristics: size, boundary, shape, internal echo, acoustic pattern, posterior features, calcification, internal blood flow, and pushing peripheral organs. Univariate and multivariate logistic regression analyses were used to assess the clinicopathologic and ultrasound variables that were associated with UFH. RESULTS There were 27 neuroblastoma cases (26.0%) of the UFH group. The independent clinicopathologic variables for the UFH were: older than one year (Odds ratio [OR]=32.84, p=0.003), presence of metastases (OR=4.92, p=0.032), and the MYCN amplification ratio &gt;5 (OR=47.06, p=0.003). The independent ultrasound feature of neuroblastoma which associated with UFH was the ill-defined boundary (OR=4.64, p=0.047) and tumor size ≥50mm (OR=15.77, p=0.05). CONCLUSION Patients older than one year, with the presence of metastases, and the MYCN amplification ratio &gt;5 on the FISH analysis as well as the ill-defined boundary and tumor size ≥50mm on an ultrasound assessment were associated with the UFH in neuroblastoma. These characteristics of the neuroblastoma should be considered in patient stratification and prognostic evaluation. Key words: Neuroblastoma; Unfavorable histology; Ultrasound
Histone 1 Mutations Drive Lymphomagenesis By Inducing Primitive Stem Cell Functions and Epigenetic Instructions through Profound 3D Re-Organization of the B-Cell Genome
Authors: Nevin Yusufova, Matthew R Teater, Alexey Soshnev, Andreas Kloetgen, Adewola Osunsade, Joseph Conway, Ashley Doane, Arthur Skoultchi, Aristotelis Tsirigos, Yael David, C. David Allis, Ethel Cesarman, Ari Melnick
Journal: Blood (2019)