tbuckley/cabot-search huggingface dataset:
Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors
Authors: Satya Das, Douglas B. Johnson
Journal: Journal for ImmunoTherapy of Cancer (2019)

Although immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for patients with many advanced malignancies, only 15–60% of patients respond, leaving a broad swath of patients who do not derive benefit. Identifying biomarkers to optimally identify patients who will benefit from ICIs is a major research focus for the oncology community. Thus far, predictive biomarker research has focused on tumor signatures such as microsatellite instability, programmed death-ligand 1 (PD-L1) expression and tumor mutational burden; clinical biomarkers have been far less studied. One potential clinical biomarker for ICI response in patients is immune-related adverse event (IRAE) onset. IRAEs are thought to represent bystander effects from activated T-cells and it is plausible that patients responding to ICIs would have greater likelihood of autoimmune toxicities (e.g. due to a more competent/treatment-responsive immune system, or cross-reactivity between tumor and host tissue). Earlier studies in melanoma patients however, suggested no association between IRAE onset and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody efficacy. In contrast, a growing body of literature suggests IRAE onset is predictive of anti-programmed cell death protein 1 (PD-1) and anti-PD-L1 antibody response across a variety of solid tumors. Most of these studies report that patients who experienced IRAEs demonstrate marked improvements in progression-free survival, overall survival and overall response rate compared to those lacking toxicity. Key questions regarding the association between IRAE onset and ICI efficacy remain. The most pertinent of these involve whether the association is only relevant for patients treated with anti-PD-1 and anti-PD-L1 antibodies and whether IRAE site, severity, timing of onset and management influence ICI efficacy. Herein, we discuss the seminal studies which have begun to address these questions and have shaped the narrative about the predictive value of IRAE onset for patients on ICIs, in this review.
Short Time to Treatment Is Associated with Inferior Survival in Newly Diagnosed Patients with Mantle Cell Lymphoma
Authors: Narendranath Epperla, Jeffrey M. Switchenko, Krithika Shanmugasundaram, Subir Goyal, Oscar Calzada, Michael C. Churnetski, Bhaskar Kolla, Veronika Bachanova, James N. Gerson, Stefan K. Barta, Max J. Gordon, Alexey Danilov, Natalie S Grover, Stephanie Mathews, Madelyn Burkart, Reem Karmali, Yazeed Sawalha, Brian T. Hill, Nilanjan Ghosh, Steven I Park, David A. Bond, Talha Badar, Kristie A. Blum, Mehdi Hamadani, Timothy S. Fenske, Mary-Kate Malecek, Peter Martin, Jin Guo, Brad S. Kahl, Christopher R. Flowers, Jonathon B. Cohen
Journal: Blood (2019)
African American Race Is Associated with Decreased Relapse-Free Survival in Immune Thrombotic Thrombocytopenic Purpura
Authors: Angela Liu, Marshall Mazepa, Elizabeth Davis, Andrew Johnson, Ana G Antun, Andrew M. Farland, Ryan R Woods, Ara Metjian, Kristin Bagby, Yara Park, Jay S Raval, Gustaaf de Ridder, Briana Gibson, Raj S. Kasthuri, Darla K Liles, Susan Eubanks, Frank Akwaa, Lisa Baumann Kreuziger, J Evan Sadler, Meera Sridharan, Ronald S. Go, Rahil Kohli, Harsh Vardhan Upreti, Keith R McCrae, Ming Y. Lim, X. Long Zheng, Nicole K. Kocher, Radhika Gangaraju, Spero Cataland, Shruti Chaturvedi
Journal: Blood (2019)
How Curiosity Enhances Hippocampus-Dependent Memory: The Prediction, Appraisal, Curiosity, and Exploration (PACE) Framework
Authors: Matthias J. Gruber, Charan Ranganath
Journal: Trends in Cognitive Sciences (2019)

Curiosity plays a fundamental role for learning and memory, but the neural mechanisms that stimulate curiosity and its effect on memory are poorly understood. Accumulating evidence suggests that curiosity states are related to modulations in activity in the dopaminergic circuit and that these modulations impact memory encoding and consolidation for both targets of curiosity and incidental information encountered during curiosity states. To account for this evidence, we propose the Prediction, Appraisal, Curiosity, and Exploration (PACE) framework, which attempts to explain curiosity and memory in terms of cognitive processes, neural circuits, behavior, and subjective experience. The PACE framework generates testable predictions that can stimulate future investigation of the mechanisms underlying curiosity-related memory enhancements.
Efficacy and Safety of CAR-T Therapy with Safety Switch Targeting Bcma for Patients with Relapsed/Refractory Multiple Myeloma in a Phase 1 Clinical Study
Authors: Weijun Fu, Juan Du, Hua Jiang, Zhi CHENG, Runhong Wei, Kang Yu, Songfu Jiang, Feng He, Hongliang Fang, Yarong Liu, Pin Wang
Journal: Blood (2019)
A Novel Machine Learning Derived Genomics-Based Scoring System Is Highly Predictive of Outcome in Core Binding Factor Acute Myeloid Leukemia
Authors: Nikhil Patkar, Chinmayee Kakirde, Anam Fatima Shaikh, Shrinidhi Nathany, Gaurav Chatterjee, Prashant Tembhare, Dhanlaxmi Lalit Shetty, Anant Gokarn, Sachin Punatar, Avinash Bonda, Lingaraj Nayak, Hasmukh Jain, Navin Khattry, Bhausaheb Bagal, Manju Sengar, Sumeet Gujral, Papagudi Ganesan Subramanian
Journal: Blood (2019)
Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1
Authors: Tetsuo Hasegawa, Junichi Kikuta, Takao Sudo, Yoshinobu Matsuura, Takahiro Matsui, Szandor Simmons, Kosuke Ebina, Makoto Hirao, Daisuke Okuzaki, Yuichi Yoshida, Atsushi Hirao, Vladimir V. Kalinichenko, Kunihiro Yamaoka, Tsutomu Takeuchi, Masaru Ishii
Journal: Nature Immunology (2019)
SURG-25. LASER INTERSTITIAL THERMAL THERAPY (LITT) FOR INTRACRANIAL LESIONS: A SINGLE- INSTITUTIONAL SERIES, OUTCOMES AND REVIEW OF THE LITERATURE
Authors: Rocco Dabecco, Alexander Yu, Tulika Ranjan, Linda Xu, Khaled Aziz
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Laser interstitial thermal therapy (LITT) is a minimally invasive treatment method that provides surgeons with cytoreductive techniques to treat neurosurgical conditions such as primary brain neoplasms, brain metastases, radiation necrosis, and epileptogenic lesions, many of which are located in operative corridors that would be difficult to address via open surgical or are amenable via minimally invasive approaches. Although the use of lasers is not a new concept in neurosurgery, advances in technology have enabled surgeons to perform laser treatment with the aid of real-time MRI thermography as a guide. In this report, we present our institutional series and outcomes of patients treated with LITT for 8 glial neoplasms 12 brain metastases. METHODS We retrospectively evaluated 20 patients (7 male, 13 female; age range, 28–77 years) who underwent LITT at one or more targets from 2015–2019. RESULTS In our series, all patients included had prior craniotomy for either primary glioma or metastatic disease. Mean extent of ablation (EOA) was 98% on post-op MRI. Mean progression free survival varied depending on the intracranial pathology, with the glioma cohort (5 months (SDD: 3.51)) demonstrating worse outcomes than metastatic disease (8.2 months (SDD: 4.83)). Only 1 patient experienced immediate post-operative morbidity, 1 patient experienced post-operative mortality secondary to hemorrhage. Mean follow-up was 9.7 months (SDD: 5.35), with one patient lost to follow up immediately post-procedure and excluded from the study. Average hospitalization was 2.4 days (SDD: 1.0). Mean overall survival, post-diagnosis of intracranial lesion, is more favorable for metastatic lesions (48 months (SDD: 27.14)), as compared to primary glial neoplasms (31 months SDD: 11.63)). CONCLUSION Laser interstitial thermal therapy (LITT) is a safe, minimally invasive treatment method that provides surgeons with cytoreductive techniques to treat neurosurgical conditions. In properly selected patients, this modality offers improved survival outcomes in conjunction with other salvage therapies.
Long Term Effects of Eltrombopag Treatment Versus Placebo for Low-Risk Myelodysplastic Syndromes with Thrombocytopenia (EQoL-MDS): Interim Results of a Single-Blind, Randomised, Controlled, Phase 2 Superiority Trial
Authors: Esther Natalie Oliva, Caterina Alati, Valeria Santini, Antonella Poloni, Marta Riva, Pasquale Niscola, Valentina Giai, Grazia Sanpaolo, Enrico Balleari, Elena Crisà, Dario Ferrero, Ulrich Germing, Pierre Fenaux, Giuseppe A. Palumbo, Prassede Salutari, Stefana Impera, Isabella Capodanno, Gianluigi Reda, Anna Marina Liberati, Alfredo Molteni, Giorgina Specchia, Francesco Buccisano, Maria Teresa Voso, Stefano Mancini, Monica Bocchia, Anna Candoni, Bruno Martino, Patrizia Cufari, Maria Grazia D'Errigo, Gina Zini, Roberto Latagliata
Journal: Blood (2019)
MYC and BCL2 mRNA Expression As Determined By NGS Predicts Survival in DLBCL in GCB but Not in ABC Subgroup
Authors: Maher Albitar, Xu‐Monette Y Zijun, Yingjun Wang, Deng Manman, Alexandar Tzankov, Carlo Visco, Govind Bhagat, Karen Dybkær, Wayne Tam, Eric D. Hsi, Maurilio Ponzoni, Andres JM Ferreri, Michael Boe Møller, Miguel A. Piris, Han van Krieken, Ivan De Dios, Youli Zu, Jane N Winter, Hagop M. Kantarjian, Yong Li, Ken H. Young
Journal: Blood (2019)
Comorbidities Reduce Response to Induction Treatment and Survival in Adults with Philadelphia-Negative Acute Lymphoblastic Leukemia
Authors: Ilaria Tanasi, Veronica Tagliaferri, Cristina Tecchio, Fiorenza Aprili, Giovanna De Matteis, Giovanni Pizzolo, Mauro Krampera, Massimiliano Bonifacio
Journal: Blood (2019)
RDNA-01. TUBULIN AND MICROTUBULES AS MOLECULAR TARGETS FOR TTFIELD THERAPY
Authors: Aarat Kalra, Sahil Patel, Asadullah Bhuiyan, Vahid Rezania, John Lewis, Karthik Shankar, Jack Tuszynski
Journal: Neuro-Oncology (2019)

Abstract TTField (Tumor-treating field) therapy utilizes low intensity intermediate frequency AC electric fields to reduce the spread of cancer. While it has attained FDA approval for the treatment of recurrent glioblastoma multiforme, the exact molecular targets of TTField therapy are not well understood. Microtubules are pipe-like polymers of the highly charged (–31 e) and strongly dipolar (dipole moment 1666 D) protein, α, β- tubulin. Studies on the electrical properties of microtubules have recently gained interest, with them being modelled as molecular targets of TTFields. Here, we experimentally show that while tubulin polymerized into microtubules leads to an increase in solution capacitance, unpolymerized tubulin has no appreciable effect. To the best of our knowledge, we present the first experimental quantification of the capacitance of a 20 μm-long microtubule. Using these results, we calculate the resonant frequency of a microtubule meshwork in a cell-like environment to be in the TTField regime. Our results utilize high ionic strength solutions and cell-like concentrations of tubulin to show the potential of microtubules as the targets of TTField action and as intracellular charge-storage devices. We conclude with a hypothesis of an electrically-tunable cell, where the dielectric properties of the cytoskeleton alter local and global charge storage and transport.
CSIG-24. GABP LINKS AMPK SIGNALING TO TERT REGULATION IN A TERT PROMOTER MUTATION DEPENDENT MANNER
Authors: Andrew McKinney, Alexandra Amen, Nicholas Stevers, Joseph Costello
Journal: Neuro-Oncology (2019)

Abstract Over 90% of human tumors achieve immortality by reactivating telomerase reverse transcriptase (TERT), the catalytic subunit of telomerase. Two mutually exclusive, heterozygous mutations that activate the TERT promoter (TERTp) occur in a wide range of cancers including ~80% of glioblastomas (GBM). The mutations and TERTp activation enable cells to avoid replicative senescence and continue to divide beyond the normal limits on cellular lifespan, thus becoming immortal. Our lab has demonstrated that each mutation creates a novel E26-transformation specific binding site that allows the tetrameric form of the GA-binding protein GABP to bind and aberrantly activate the mutant TERTp. We further showed that reducing a tetramer-forming subunit of GABP, the GABPB1L transactivating subunit, reverses cellular immortality in vitro and reduces tumor growth in vivo. Beyond GABP, little is known about pathways that contribute to immortality via activation of the mutant TERTp. The heterotrimeric 5’ AMP-activated protein kinase (AMPK) complex is activated in human GBM compared to normal brain, and was previously implicated in regulating GABP expression. Here, we have determined that AMPK inhibition decreases transcription of both subunits of the tetrameric GABP complex (GABPA and GABPB1L) in GBM cells, and is sufficient to reduce TERT expression and telomerase activity in a TERT promoter mutation dependent manner. Together, these data suggest a novel and targetable connection between the AMPK signaling axis, telomerase activity and potentially tumor cell immortality.
Fludarabine, Cytarabine, G-CSF and Gemtuzumab Ozogamicin (FLAG-GO) Regimen Results in Better Molecular Response and Relapse-Free Survival in Core Binding Factor Acute Myeloid Leukemia Than FLAG and Idarubicin (FLAG-Ida)
Authors: Gautam M. Borthakur, Jorge E. Cortes, Farhad Ravandi, Guillermo Garcia-Manero, Tapan M. Kadia, Elias Jabbour, Keyur Patel, Ghayas C. Issa, Naval G. Daver, Maro N. Ohanian, Mark Brandt, Hagop M. Kantarjian
Journal: Blood (2019)
RARE-18. CLINICAL EXPERIENCE OF DABRAFENIB IN COMBINATION WITH TRAMETINIB TREATMENT FOR ANAPLASTIC PXA CASES
Authors: Takashi Maruyama, Yoshihiro Muragaki, Syunsuke Tsuzuki
Journal: Neuro-Oncology (2019)

Abstract Anaplastic PXA is classed as grade III tumor because of its aggressive behavior in 2016 WHO classification. Typical treatment of PXA is gross total resection followed by radiotherapy and cytotoxic chemotherapy at recurrence. Despite aggressive behavior of anaplastic PXA, there is some evidence for the use of BRAF inhibitors in BRAF V600 mutant PXA. We report two cases of successful treatment with BRAF-MEK inhibitor combination therapy (dabrafenib plus trametinib). A 19 year-old man initially diagnosed as PXA for rt temporal tumor. Subtotal removal and following 30Gy radiation was performed. After eight years, the recurrent tumor was removed subtotally and diagnosed as anaplastic PXA. Residual tumor and distant metastasis region were completely disappeared by Dabrafenib-Trametinib therapy. Tumor was diagnosed as BRAF V600 mutant and TERT wt. A 30 year-old female initially diagnosed as PXA for rt temporal cystic tumor. She was treated with subtotal removal followed by stereotactic radiosurgery. Instead of Gd-total removal, tumor recurred six times. Chemotherapy with alkyl-agent did not respond. Tumor at first surgery was diagnosed as grade II PXA. Tissues collected after SRS showed malignant feature and diagnosed as anaplastic PXA. All five specimens showed BRAF V600 mutation and additional TERT mutation was confirmed after SRS treatment. She showed paraparesis because of thoracic metastases then Dabrafenib-Trametinib therapy was started. Thoracic tumor showed PR and no remarkable recurrence in intracranial region for more than eight months, so far. BRAF and MEK inhibitor combination treatment are thought to have potential for BRAF V600 mutant NSCLC and melanoma. Anaplastic PXA with BRAF V600 mutation could be another target for the treatment.
A Phase 1 Study Evaluating BI 765063, a First in Class Selective Myeloid Sirpa Inhibitor, As Stand-Alone and in Combination with BI 754091, a Programmed Death-1 (PD-1) Inhibitor, in Patients with Advanced Solid Tumours
Authors: Jean-Pierre Delord, Nuria Kotecki, Aurelien Marabelle, Armelle Vinceneux, Iphigenie Korakis, Christiane Jungels, Stéphane Champiat, Richard D. Huhn, Nicolas Poirier, Dominique Costantini, Bérangère Vasseur, Philippe A. Cassier
Journal: Blood (2019)
Correction: EGFR Cooperates with EGFRvIII to Recruit Macrophages in Glioblastoma
Authors: Zhenyi An, Christiane B. Knobbe-Thomsen, Xiaohua Wan, Qi Wen Fan, Guido Reifenberger, William A. Weiss
Journal: Cancer Research (2019)

In the original version of this article (1), two panels were mistakenly labeled as Fig. 1E. The error has been corrected in the latest online HTML and PDF versions of the article. The authors regret this error.
Prospective, Multicentric Phase II Randomized Trial Comparing the Efficacy of Methotrexate or Cyclophosphamide in Large Granular Lymphocytic Leukemia: A French National Study. Report on the Interim Analysis
Authors: Thierry Lamy, Cedric Pastoret, Roch Houot, Loic Ysebaert, Mathilde Hunault, Gandhi Damaj, Anne Banos, Olivier Tournilhac, Bachra Choufi, Jean-Pierre Marolleau, Jehan Dupuis, Alain Jacques Delmer, Stephane Lepretre, Emmanuel Gyan, Pierre Feugier, Sophie Rigaudeau, Anne Lazareth, Jean Valère Malfuson, Thierry Fest, Eric Bellissant
Journal: Blood (2019)
NIMG-76. RADIOPATHOMICS: INTEGRATION OF RADIOGRAPHIC AND HISTOLOGIC CHARACTERISTICS FOR PROGNOSTICATION IN GLIOBLASTOMA
Authors: Saima Rathore, MacLean Nasrallah, Zissimos Mourelatos
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Large number of diverse imaging [e.g., multi-parametric MRI (mpMRI), and digital pathology images] and non-imaging (e.g., clinical) biomedical data streams are being routinely acquired as part of the standard clinical workflow for glioblastoma patients. However, under the current clinical practice, these data streams are not collectively used for diagnosis. We sought to assess the synergies between pathologic, and radiomic features by evaluating the predictive value of each group of features and their combinations through a prognostic classifier. METHODS The mpMRI (T1,T1-Gd,T2,T2-FLAIR) and corresponding digital pathology images for 135 de novo glioblastoma was acquired from TCIA. An extensive panel of handcrafted features, including shape, volume, intensity distributions, gray-level co-occurrence matrix based texture, was extracted from delineated tumor regions of mpMRI scans. A set of 100 region-of-interest each comprising 1024x1024 that contained viable tumor with descriptive histologic characteristics and that were free of artifacts were extracted from digital pathology images, and were quantified in terms of nuclear texture features, and nuclear intensity and gradient statistics. A support vector regression multivariately integrated these features towards a marker of overall-survival. The accuracy of the predictive model for each group of features, and their combinations, was determined via a 10-fold cross-validation scheme. RESULTS The Pearson correlation coefficient between the survival scores predicted by SVR and the actual survival scores was estimated to be 0.75 and 0.77 for radiographic and pathologic data, however, the integration of these data yielded a clear improvement in correlation (0.81), supporting the synergistic value of these features in the prognostic model. CONCLUSION Radiomic features extracted from preoperative mpMRI, when used together with digital pathology features, offer synergistic value in assessment of prognosis in individual patients. The proposed radiopathomics marker may contribute to (i) stratification of patients into clinical trials, (ii) patient selection for targeted therapy, and (iii) personalized treatment planning.
Oncostatin M Is a Novel Niche Factor That Restrains Hematopoietic Stem Cell Mobilization in Response to G-CSF and CXCR4 Antagonist Plerixafor
Authors: Kavita Bisht, Crystal McGirr, Kylie A Alexander, Whitney Fleming, Natalie Sims, Gerhard Müller- Newen, Ingrid G Winkler, Jean-Pierre Levesque
Journal: Blood (2019)
CD19-Targeting CAR-T Cell Therapy in CNS Lymphoma
Authors: Tanya Siddiqi, Xiuli Wang, Joycelynne Palmer, Leslie L. Popplewell, Liana Nikolaenko, Alex F. Herrera, Lihua E Budde, Laura Lim, Vibhuti Vyas, Christine E Brown, Stephen J. Forman
Journal: Blood (2019)
Ofatumumab Plus Hypercvad/MA Induction Leads to High Rates of Minimal Residual Disease (MRD) Negativity in Patients with Newly Diagnosed Mantle Cell Lymphoma, Results of a Phase 2 Study
Authors: Pallawi Torka, Nishitha Reddy, Adrienne Groman, Angela Kader, Jenna Nichols, Alan Hutson, Cory Mavis, Joseph Dennis Tario, Paul K. Wallace, AnneMarie W. Block, Sheila N. J. Sait, Bora E Baysal, Vishala T. Neppalli, Suchitra Sundaram, Francisco J. Hernandez-Ilizaliturri
Journal: Blood (2019)
Induction of labour and perinatal mortality. (letter)
Authors: Leeson J, Smith A
Journal: BMJ (1977)

In answer to an article by McNay et al. the authors caution that data presented does not necessarily suggest that increased use of induction of labor improves perinatal mortality rate.  A table plotting their annual induction and perinatal mortality rates together with Scottish perinatal mortality data shows a less clear relationship than suggested. At several points the McNay induction rate mortality is above mortality  levels for Scotland in general. More rigorous appraisal of the controversial topic is needed.
One vs 12 Months of Dual Antiplatelet Therapy for Patients After Percutaneous Coronary Intervention
Authors: Wei Keith Tan
Journal: JAMA (2019)

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