tbuckley/cabot-search huggingface dataset:
Detection of PIK3CA mutation by circulating DNA during chemotherapy: A tool to identify hard-to-treat metastatic breast cancers
Authors: F. Mosele, A. Lusque, A. Tran Dien, N. Droin, C. Le Tourneau, M.P. Sablin, L. Lacroix, I. Miran, C. Jovelet, I. Bieche, J-C Soria, F. Bertucci, H. Bonnefoi, M. Campone, F. Dalenc, T. Bachelot, A. Jacquet, M. Jimenez, F. André
Journal: Annals of Oncology (2019)
Severe allergic reaction to vaping prompts warning from doctors
Authors: Lynn Eaton
Journal: BMJ (2019)

A Nottinghamshire paediatrician has reported a severe immune reaction in a 16 year old boy who had been smoking e-cigarettes. The incident comes amid growing concerns at the safety of the products, following reports of an increasing number of deaths among users in the US.

The case study in the Archives of Disease in Childhood 1 warns that the fluid in e-cigarettes may cause a potentially life threatening lung inflammation in those who are susceptible to it.

“Coming from a paediatric perspective, we remain concerned that young adults are experimenting with e-cigarettes,” said the study’s lead author, Jayesh Mahendra Bhatt, from the Department of …
RTHP-30. DOES THE TEMPORAL LOBECTOMY CAVITY NEED TO BE IRRADIATED? PATTERNS OF RECURRENCE AND IMPLICATIONS FOR POSTOPERATIVE RADIATION TREATMENT FIELD DESIGN FOR TEMPORAL LOBE GLIOMAS.
Authors: Achiraya Teyateeti, Connie Geno, Paul Brown, Krishan Jethwa, Scott Stafford, Nadia Laack, Anita Mahajan, Elizabeth Yan, Ian Parney, Kenneth Merrell
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Treatment of temporal lobe glioma (TLG) frequently includes partial or complete temporal lobectomy (TL) followed by radiotherapy (RT). However, there are two approaches for temporal resection cavity RT, 1) standard target volumes (STV) targeting the entire TL resection cavity, dura, and peri-tumoral brain parenchyma or 2) modified target volumes (MTV) targeting only the adjacent peri-tumoral brain parenchyma. We report patterns of failure and a dosimetric comparison of these approaches. MATERIALS AND METHODS This was a retrospective review of 49 patients with WHO grade II-IV TLG who underwent partial or complete TL and post-operative RT between 1998 and 2018. Progression-free survival (PFS) was estimated using the Kaplan-Meier method. RESULTS The median patient age was 56 years (range,21–76). Patients were diagnosed with glioblastoma (n=32,65%), anaplastic glioma (n=10,20%) and low-grade glioma (n=7,14%). Treatment included partial TL with STV (n=33,67%), partial TL with MTV (n=5,10%), complete TL with STV (n=8,16%) and complete TL with MTV (n=3,6%). Mean RT dose was 60 Gy (range,40–76) in 30 fractions (range,15–39). At median follow-up time of 18 months (range, 3–161), 44 patients (90%) experienced recurrence: 34 (77%) in-field, 5 (11%) out-of-field, and 5 (11%) both in- and out-of-field. Among the 39 in-field failures, the location of recurrence included brain parenchyma (n=38,97%), ventricle (n=6,15%), and dura (n=5,13%). No patient experienced isolated dural recurrence regardless of tumor grade, extent of TL, or radiation volume. Median PFS was 20 months (95% confidence interval [CI]: 15–24). RT volume (STV vs. MTV) was not associated with worsened PFS (hazard ratio: 1.1, 95% CI: 0.5–2.6). MTV was associated with significant reductions in mean or max doses to brain stem, optic chiasm, optic nerves, hippocampus, and pituitary compared to STV. CONCLUSION Omitting RT to the entire TL cavity may reduce dose to multiple normal tissues with no detriments in dural recurrence or PFS.
Updated Follow-up of the Alta Study, a Phase 1/2, Open Label, Adaptive, Dose-Ranging Study to Assess the Safety and Tolerability of SB-525 Gene Therapy in Adult Patients with Severe Hemophilia A
Authors: Barbara A. Konkle, Kimo Stine, Nathan Visweshwar, Thomas J. Harrington, Andrew D. Leavitt, Adam Giermasz, Steven Arkin, Gregory Di Russo, Ashley Snyder, Adrian Woolfson, Didier Rouy
Journal: Blood (2019)
Insulin sensitizer MSDC-0602K in non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled phase IIb study
Authors: Stephen A. Harrison, Naim Alkhouri, Beth A. Davison, Arun Sanyal, Christopher Edwards, Jerry R. Colca, Bo Hyun Lee, Rohit Loomba, Kenneth Cusi, Orville Kolterman, Gad Cotter, Howard C. Dittrich
Journal: Journal of Hepatology (2019)
Cxcr4 low FLT3/ITD+ Cells Exhibit Enhanced Resistance to the FLT3 Inhibitor Quizartinib Compared to Cxcr4 high FLT3/ITD+ Cells By Elevating Runx1 Expression
Authors: Seiji Fukuda, Chie Onishi, Takeshi Taketani
Journal: Blood (2019)
Highly Reduced Survival in ET and PV Patients with Vascular Complications during Follow-up - Real World Data from the Swedish MPN Registr
Authors: Marie Lindgren, Erik Ahlstrand, Helna Pettersson, Maria Liljeholm, Anna Ravn-Landtblom, Stefan Scheding, Björn Andréasson, Jan Samuelsson
Journal: Blood (2019)
CXCR4 Mutational Status Does Not Impact Outcomes in Patients with Waldenstrom Macroglobulinemia Treated with Proteasome Inhibitors
Authors: Jorge J. Castillo, Joshua Gustine, Maria Demos, Andrew Keezer, Kirsten Meid, Toni Dubeau, Gloria G Chan, Jiaji Chen, Maria Luisa Guerrera, Amanda Kofides, Manit Munshi, Nicholas Tsakmaklis, Xia Liu, Lian Xu, Guang Yang, Zachary R Hunter, Steven P Treon
Journal: Blood (2019)
Pilot Study of Telmisartan (Micardis) for Prevention of Acute Graft Vs. Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation: Interim Analysis
Authors: Sujatha Iyengar, Scott D. Rowley, Caixin Zhan, Michele L. Donato, Themba Nyirenda, David H. Schwartz
Journal: Blood (2019)
TMIC-59. INVESTIGATING PHYSIOLOGY OF THERAPY RESISTANT, TUMOR-INITIATING GBM CELLS IN HYPOXIC NICHES USING SPATIALLY-SENSITIVE HYPOXIA REPORTER SYSTEM AND SINGLE-CELL RNA SEQUENCING
Authors: Anirudh Sattiraju, Valerie Marallano, Roland Friedel, Hongyan Zou
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma (GBM) is the most common and lethal brain cancer that invariably recurs after therapy due to presence of resistant GBM cells within hypoxic and peri-necrotic regions. Eradicating such GBM cells, which constitute a major source of tumor recurrence, is important to curb disease relapse. An endogenously expressed, spatially sensitive hypoxia reporter would therefore be a valuable tool to evaluate hypoxic zones in GBM in detail, and to measure the efficacy of hypoxia-activated drugs. For this purpose, we engineered a lentiviral vector that carries a hypoxia reporter, consisting of HIF response elements (HRE) that drive expression of UnaG fluorescent protein, which fluoresces independent of oxidative maturation. We validated the sensitivity of our reporter in vitro using U87MG, GBM2, and patient-derived GBM stem cell lines, and we performed intracranial transplantations of GBM cells in SCID mice to identify cells undergoing hypoxic stress in in vivo microenvironment. In addition, GL261 murine GBM cells with hypoxia reporter were intracranially implanted in C57BL/6 mice as syngeneic model for studies on immune responses. Brains from our transplant studies were dissociated and single-cell RNA sequencing (Drop-Seq) was performed to investigate heterogeneity in response to hypoxia within GBM cells and the cellular composition of microenvironment. We will also apply a hypoxia-activated prodrug, Evofosfamide (Evo), in our ongoing studies that can potentially eradicate hypoxic tumor cells and increase T cell infiltration and reverse immune suppression. As hypoxic niches are thought to confer resistance to radiation therapy (XRT), combining XRT with Evo could thus improve therapy efficacy. Our hypoxia gene reporter, combined with single-cell transcriptomics, could therefore serve as an effective tool to enable fundamental investigation of GBM microenvironment and could be used to evaluate therapies targeting tumor microenvironment to enhance GBM patient survival.
US Optum Database Study in Polycythemia Vera Patients: Thromboembolic Events (TEs) with Hydroxyurea (HU) Vs Ruxolitinib Switch Therapy and Machine-Learning Model to Predict Incidence of Tes and HU Failure
Authors: Srdan Verstovsek, Valerio De Stefano, Florian H. Heidel, Mike Zuurman, Michael Zaiac, Erwan Bigan, Michael Ruhl, Christoph Meier, Magali Beffy, Jean-Jacques Kiladjian
Journal: Blood (2019)
Conventional Real Time Quantitative Polymerase Chain Reaction Method Yields Similar Level of Sensitivity to Digital Droplet Polymerase Chain Reaction for Detection of BCR-ABL p210 Transcripts in Patients with Chronic Phase Chronic Myeloid Leukemia
Authors: Hannah Asghari, Chetasi Talati, Alexandra Achille, John J. Powers, Eva Sahakian, Onyee Chan, Dawne N Shelton, Leidy Isenalumhe, Lisa Nodzon, Kendra L. Sweet, Javier Pinilla Ibarz
Journal: Blood (2019)
Molecular Characterization of Leukemia Evolving from Paroxysmal Nocturnal Hemoglobinuria
Authors: Hassan Awada, Shafia Rahman, Cassandra M Kerr, Jibran Durrani, Vera Adema, Ashwin Kishtagari, Sunisa Kongkiatkamon, Hetty E. Carraway, Mikkael A. Sekeres, Jaroslaw P. Maciejewski, Valeria Visconte
Journal: Blood (2019)
The Risk of Hepatitis B Reactivation Is Controllable in Patients with Concomitant Hepatitis B Virus Infection during Chimeric Antigen Receptor T-Cell Therapy
Authors: Wei Liu, Rui Lv, Wenyang Huang, Hong Liu, Shuhui Deng, Shuhua Yi, Lulu Lv, Jianxiang Wang, Lugui Qiu, Dehui Zou
Journal: Blood (2019)
Developmental and cellular age direct conversion of CD4+ T cells into RORγ+ or Helios+ colon Treg cells
Authors: Alvin Pratama, Alexandra Schnell, Diane Mathis, Christophe Benoist
Journal: The Journal of Experimental Medicine (2019)

RORγ+ and Helios+ Treg cells in the colon are phenotypically and functionally distinct, but their origins and relationships are poorly understood. In monocolonized and normal mice, single-cell RNA-seq revealed sharing of TCR clonotypes between these Treg cell populations, potentially denoting a common progenitor. In a polyclonal Treg cell replacement system, naive conventional CD4+ (Tconv) cells, but not pre-existing tTregs, could differentiate into RORγ+ pTregs upon interaction with gut microbiota. A smaller proportion of Tconv cells converted into Helios+ pTreg cells, but these dominated when the Tconv cells originated from preweaning mice. T cells from infant mice were predominantly immature, insensitive to RORγ-inducing bacterial cues and to IL6, and showed evidence of higher TCR-transmitted signals, which are also characteristics of recent thymic emigrants (RTEs). Correspondingly, transfer of adult RTEs or Nur77high Tconv cells mainly yielded Helios+ pTreg cells, recapitulating the infant/adult difference. Thus, CD4+ Tconv cells can differentiate into both RORγ+ and Helios+ pTreg cells, providing a physiological adaptation of colonic Treg cells as a function of the age of the cell or of the individual.
Primary lymphosarcoma of the lung
Authors: G. M. Rees
Journal: Thorax (1973)

<b>Rees, G. M. (1973).</b><i>Thorax</i>, <b>28</b>, 429-432. <b>Primary lymphosarcoma of the lung.</b> All cases of primary lymphosarcoma of the lung seen at Brompton Hospital over the last 20 years are reviewed. Clinical features and the results of special investigations are discussed together with an analysis of the results of different forms of treatment.
NCOG-06. PILOT STUDY OF NEUROCOGNITIVE DECLINE IN MALIGNANT GLIOMA PATIENTS TREATED WITH CHEMORADIATION AND ADJUVANT CHEMOTHERAPY
Authors: Ivette Emery, Frances Lucas, Sarah Vreeland, Deborah Cushing, Dana Tripp, Thomas Miller, Christine Lary, Christine Lu-Emerson
Journal: Neuro-Oncology (2019)

Abstract The majority of glioma patients experience declines in neurocognitive function (NCF), presumably due to tumor and treatment effects. We sought to understand the natural history of this decline in grade III and grade IV patients. A condensed battery of cognitive tests (HTLV, COWAT, GPT, TMT, and BTA) was administered at three time points: prior (T0) and after (T1) chemoradiation, and during adjuvant chemotherapy (T2). 31 patients were enrolled of which 25, 9 grade III and 16 grade IV, were analyzed. Although our N was too small for statistically significant results, we observed potentially meaningful clinical trends. Changes in HTLV, TMT, and COWAT scores among grade III patients displayed a pattern different from that of grade IV, with a steep decline seen after chemoradiation (T0-T1) followed by improvement several months later (T1-T2), despite ongoing chemotherapy. Grade IV patients, in contrast, showed minimal decline in scores (little change in score between T0-T1 and between T1-T2), perhaps highlighting that NCF is more impacted by disease rather than treatment. We tried to identify a subset of patients who seemed more susceptible to NCF decline. Examination of key clinical features showed that less than gross total resection and less than 4 year degree education level trended to associate with steeper NCF decline (only 40% of those experiencing steep declines in multiple domains had more than 4 yr degree, versus 60% of those with moderate or no decline). This pilot study highlights that assessing neurocognitive function routinely in clinical practice is feasible in a rural academic hospital. Based on patterns of changes in NCF, it appears that grade III and grade IV gliomas are distinct tumor subtypes with respect to NCF decline. Level of education may be a useful biomarker to identify those patients most at risk for neurocognitive decline after treatment.
Phase II Window Study of Pembrolizumab in Untreated B-Cell Non-Hodgkin Lymphoproliferative Diseases
Authors: Ajay K. Gopal, Adam Greenbaum, Ryan C. Lynch, Edus H. Warren, Chaitra S. Ujjani, Mazyar Shadman, Stephen D. Smith, Brian G. Till, Jonathan R. Fromm, Andrei R Shustov, Qian Vicky Wu, Manoj P. Menon
Journal: Blood (2019)
Impact of Precision Medicine on Efficiencies of Novel Drug Development in Cancer
Authors: Holly Sarvas, Benjamin Carlisle, Samantha Dolter, Esther Vinarov, Jonathan Kimmelman
Journal: JNCI Journal of the National Cancer Institute (2019)

Precision medicine (PM) offers opportunities for reducing the costs, burdens, and time associated with drug development. We examined time, number of trials, indications tested, and patient burden needed to achieve first U.S. Food and Drug Administration license for all five novel anticancer PM drugs and all 10 novel non-PM drugs receiving U.S. Food and Drug Administration approval during 2010-2014. The 15 drug portfolios encompassed 242 trials: 87 for PM drugs and 155 for non-PM drugs. Embase and MEDLINE databases were searched for all prelicensure clinical trials, and data on time, patient numbers, indications tested, and total treatment-emergent grade 3-5 adverse events were measured from the first trial of each drug. We did not find patterns suggesting greater efficiencies in PM compared with non-PM. Gains in efficiency for PM drug development may be offset by challenges with recruitment.
A Population-Based Cohort Study Examining the Incidence and Impact of Psychotic Experiences From Childhood to Adulthood, and Prediction of Psychotic Disorder
Authors: Sarah A. Sullivan, Daphne Kounali, Mary Cannon, Anthony S. David, Paul C. Fletcher, Peter Holmans, Hannah Jones, Peter B. Jones, David E.J. Linden, Glyn Lewis, Michael J. Owen, Michael O’Donovan, Alexandros Rammos, Andrew Thompson, Dieter Wolke, Jon Heron, Stanley Zammit
Journal: American Journal of Psychiatry (2020)

The authors investigated the incidence, course, and outcome of psychotic experiences from childhood through early adulthood in the general population and examined prediction of psychotic disorder.This was a population-based cohort study using the semistructured Psychosis-Like Symptoms Interview at ages 12, 18, and 24 (N=7,900 with any data). Incidence rates were estimated using flexible parametric modeling, and positive predictive values (PPVs), sensitivity, specificity, and area under the curve were estimated for prediction.The incidence rate of psychotic experiences increased between ages 13 and 24, peaking during late adolescence. Of 3,866 participants interviewed at age 24, 313 (8.1%, 95% CI=7.2, 9.0) had a definite psychotic experience since age 12. A total of 109 individuals (2.8%) met criteria for a psychotic disorder up to age 24, of whom 70% had sought professional help. Prediction of current psychotic disorder at age 24 (N=47, 1.2%), by both self-report and interviewer-rated measures of psychotic experiences at age 18 (PPVs, 2.9% and 10.0%, respectively), was improved by incorporating information on frequency and distress (PPVs, 13.3% and 20.0%, respectively), although sensitivities were low. The PPV of an at-risk mental state at age 18 predicting incident disorder at ages 18-24 was 21.1% (95% CI=6.1, 45.6) (sensitivity, 14.3%, 95% CI=4.0, 32.7).The study results show a peak in incidence of psychotic experiences during late adolescence as well as an unmet need for care in young people with psychotic disorders. Because of the low sensitivity, targeting individuals in non-help-seeking samples based only on more severe symptom cutoff thresholds will likely have little impact on population levels of first-episode psychosis.
Higher Expression of Nuclear Cereblon in Bone Marrow Biopsies of Patients with Multiple Myeloma Treated with Imids in the HOVON-87/Nmsg-18 Trial Is Associated with Longer PFS and OS
Authors: Ruth Wester, M Duin, King Hong Lam, Suzana Couto, Yan Ren, Maria Wang, Bronno Van Der Holt, Berna Berna Beverloo, Heleen Visser-Wisselaar, Alex Nigg, Anjan Thakurta, Sonja Zweegman, Annemiek Broyl, Pieter Sonneveld
Journal: Blood (2019)
Significance of Abnormalities of PPM1D in Myeloproliferative Neoplasms
Authors: Bridget Marcellino, Joseph Tripodi, Michal Bar-Natan, Harry Fruchtman, Noushin Farnoud, Min Lu, Heidi E. Kosiorek, Amylou C. Dueck, Raajit K. Rampal, John Mascarenhas, Vesna Najfeld, Ronald Hoffman
Journal: Blood (2019)
CMET-12. EFFICACY OF UPFRONT IMMUNE CHECKPOINT INHIBITORS IN LUNG CANCER BRAIN METASTASIS
Authors: Addison Barnett, Adam Lauko, Hong Li, Assad Ali, Soumya Sagar, Samuel Chao, Nathan Pennell, David Peereboom, Glen Stevens, Lilyana Angelov, Jennifer Yu, Erin Murphy, Alireza Mohammadi, John Suh, Gene Barnett, Manmeet Ahluwalia
Journal: Neuro-Oncology (2019)

Abstract INTRO/OBJECTIVE Immune checkpoint inhibitors (ICI) have improved outcomes in a subset of patients with lung cancer. However, data describing the efficacy of ICI in lung cancer brain metastasis (LCBM) is limited. We analyzed overall survival (OS) in patients with LCBM treated with upfront ICI, defined as having received ICI within 90-days of LCBM diagnosis, compared to non-ICI therapies. METHODS We reviewed 665 patients with LCBM diagnosed between 2000 and 2018 at a major tertiary care institution. Of those patients, 240 received ICI, 164 of which received ICI after 90-days and 76 received ICI within 90-days. Propensity score (PS) was calculated by logistic regression model including age, KPS, number of baseline brain lesions, and presence of extra-cranial metastasis (ECM) at time of LCBM diagnosis. OS from LCBM diagnosis between PS matched cohorts were compared using Kaplan-Meier, the Log-Rank test, and Cox proportional hazards models. RESULTS Prior to PS matching, median survival between ICI and non-ICI cohorts was not significantly different (10.9 months for both, p=0.81), although more ICI patients had ECM (57.1% vs 40.9%, p=0.006). Following PS matching, the ICI (n=76) and non-ICI (n=76) cohorts had median age (62.4 vs 62.3 years), KPS (80 for both), lesion number (2 for both), and ECM (56.6% for both). Of matched patients, 94% received SRS, 52% received WBRT, and 29% underwent surgical resection. Compared to non-ICI, the ICI cohort had a 2-year OS hazard ratio=0.87 (95% CI=0.58–1.31, p=0.51). Median and 1-year survival were not significantly different between ICI and non-ICI cohorts (median: 10.9 vs 9.1 months; 1-yr: 43.0% vs 42.4%). CONCLUSION Patients with LCBM who received ICI within 90-days of their diagnosis did not have improvement in OS compared to patients who received non-ICI therapies. Evaluation of clinical factors that may affect the efficacy and durability of immunotherapy is ongoing and will be presented.
Patients with hidradenitis suppurativa may suffer from neuropathic pain: A Finnish multicenter study
Authors: Laura Huilaja, Mirkka J. Hirvonen, Tiina Lipitsä, Armi Vihervaara, Rauno Harvima, Harri Sintonen, Jukka Pekka Kouri, Martta Ranta, Rafael Pasternack
Journal: Journal of the American Academy of Dermatology (2019)
Preclinical Characterization of Prgn-3006 Ultracar-T™ for the Treatment of AML and MDS: Non-Viral, Multigenic Autologous CAR-T Cells Administered One Day after Gene Transfer
Authors: Tim Chan, Xiaohong Ma, Fernando Carvajal-Borda, Jose Velez, Jacques Plummer, Lindsey Shepard, Rutul R Shah, David A Sallman, Helen Sabzevari
Journal: Blood (2019)
Fueling ab initio folding with marine metagenomics enables structure and function predictions of new protein families
Authors: Yan Wang, Qiang Shi, Pengshuo Yang, Chengxin Zhang, S. M. Mortuza, Zhidong Xue, Kang Ning, Yang Zhang
Journal: Genome biology (2019)

Abstract Introduction The ocean microbiome represents one of the largest microbiomes and produces nearly half of the primary energy on the planet through photosynthesis or chemosynthesis. Using recent advances in marine genomics, we explore new applications of oceanic metagenomes for protein structure and function prediction. Results By processing 1.3 TB of high-quality reads from the Tara Oceans data, we obtain 97 million non-redundant genes. Of the 5721 Pfam families that lack experimental structures, 2801 have at least one member associated with the oceanic metagenomics dataset. We apply C-QUARK, a deep-learning contact-guided ab initio structure prediction pipeline, to model 27 families, where 20 are predicted to have a reliable fold with estimated template modeling score (TM-score) at least 0.5. Detailed analyses reveal that the abundance of microbial genera in the ocean is highly correlated to the frequency of occurrence in the modeled Pfam families, suggesting the significant role of the Tara Oceans genomes in the contact-map prediction and subsequent ab initio folding simulations. Of interesting note, PF15461, which has a majority of members coming from ocean-related bacteria, is identified as an important photosynthetic protein by structure-based function annotations. The pipeline is extended to a set of 417 Pfam families, built on the combination of Tara with other metagenomics datasets, which results in 235 families with an estimated TM-score over 0.5. Conclusions These results demonstrate a new avenue to improve the capacity of protein structure and function modeling through marine metagenomics, especially for difficult proteins with few homologous sequences.
Large-Scale Manufacturing of CMV-CD19CAR T Cells and Characterization of Their Biologic and Immunologic Properties
Authors: Xiuli Wang, Miriam Walter, Ryan Urak, Laura Lim, Vibhuti Vyas, Sally Mokhtari, Don J. Diamond, Angelo Cardoso, John Zaia, Stephen J. Forman, Ryotaro Nakamura
Journal: Blood (2019)