tbuckley/cabot-search huggingface dataset:
REPORTS OF SOCIETIES
Authors: H O CLARKE
Journal: BMJ (1947)

of the Royal Society of Medicine on Nov. 21, with Dr. J. S. FULTON in the chair, Dr. ELIS BERVEN, of Stockholm, gave an account of the methods and results of radiation treatment of malignant tumours in Radiumhemmet.Dr. Berven said that one of the principles followed was that radiation through the tissues surrounding the tumour must not be of such intensity as to damage the resistance of the body, and another was that treatment should be given in the shortest possible time.He described the x-ray and other apparatus employed, and said that 3,225 mg. of radium was distributed in 97 tubes and 14 applicators.Only gamma rays were used, and no radium emanation or radon was employed.Malignant melanoma, which was radio-resistant, was treated by excision under general anaesthesia, followed by prophylactic x-ray or radium treatment in the region.In carcinoma of the lip radium applicators had been used at first, and then implantation of radium needles, but now most cases were treated by x rays and 69% of patients were symptom-free after five years.In cases of carcinoma of the mouth radium applicators and implanted -radium needles had given way to a combined method, beginning with teleradium through different ports of entry so as to give a cross-fire effect, supplemented later by x-ray treatment.Usually a small tumour remnant was left, and this was electro- coagulated under general anaesthesia.Cases of cancer of the oral cavity treated in this way in the period 1931-41 numbered 688, of which 196, or 28.5%, were symptom-free at the end of five years.He next spoke of the Plummer-Vinson syndrome.The atrophic state of the mucous membrane of the mouth seemed to predispose these patients to tumours of a malignant type.X-ray treatment was applied in four fields, two on each side, each field being given a total of from 2,000 to 3,000 r in daily doses of 400 r, and later teleradium was applied.For tumours of the oesophagus only palliative treatment could be undertaken.
Long Term Follow-up of a Phase II Study of Cladribine with Concurrent Rituximab in Patients with Hairy Cell Leukemia Variant
Authors: Dai Chihara, Evgeny Arons, Maryalice Stetler-Stevenson, Constance M. Yuan, Hao-Wei Wang, Hong Zhou, Mark Raffeld, Liqiang Xi, Seth M. Steinberg, Julie Feurtado, Lacey James-Echenique, Wyndham Wilson, Raul C. Braylan, Katherine R. Calvo, Irina Maric, Alina Dulau-Florea, Robert J. Kreitman
Journal: Blood (2019)
An e13a2 Type of BCR-ABL Transcript Has a Significant Adverse Impact on the Achievement of a Sustained Deep Molecular Response and on the Maintenance of a Treatment Free Remission after Stopping Tyrosine Kinase Inhibitors
Authors: Mariella D'adda, Mirko Farina, Francesca Schieppati, Elisa Cerqui, Giuseppina Ruggeri, Samantha Ferrari, Chiara Bottelli, Chiara Pagani, Angela Passi, Giuseppe Rossi
Journal: Blood (2017)
Disruption of Oligodendrogenesis Impairs Memory Consolidation in Adult Mice
Authors: Patrick E. Steadman, Frances Xia, Moriam Ahmed, Andrew J. Mocle, Amber R.A. Penning, Anna C. Geraghty, Hendrik W. Steenland, Michelle Monje, Sheena A. Josselyn, Paul W. Frankland
Journal: Neuron (2019)
Distinct Escape Mechanisms of HLA Class I Allele-Lacking Hematopoietic Stem Progenitor Cells (HSPCs) from GPI-Deficient HSPCs in Acquired Aplastic Anemia
Authors: Noriaki Tsuji, Kohei Hosokawa, Takeshi Yoroidaka, Tanabe Mikoto, Hiroki Mizumaki, Shinji Nakao
Journal: Blood (2019)
Intravital Imaging of Bright Cyan-Fluorescent AML Model Reveals Impact of CXCR4 Inhibitor on AML and Immune Cell Dynamics
Authors: Tomasz Zal, Mateusz Rytelewski, Rodrigo Jacamo, Malgorzata Anna Zal, Meenakshi Shanmugasundaram, Michael Andreeff
Journal: Blood (2019)
CBMT-06. HIGH LEVELS OF GATA-4 IN MALIGNANT MENINGIOMA LEAD TO LOWER miR-497~195 CLUSTER EXPRESSION IN TISSUE AND BLOOD
Authors: Catarina Negroni, Emanuela Ercolano, Claire Adams, Daniele Baiz, Kathreena M Kurian, David Hilton, Clemens Oliver Hanemann
Journal: Neuro-Oncology (2019)

Abstract Meningioma is the most common primary intracranial brain tumour, classified as benign (WHO I, 70%), atypical (WHO II, 30%) and anaplastic/malignant (WHO III, 1–3%). The 3-year recurrence rate for WHO I tumours is 40% and it is much higher in WHO II-III1. To date, meningioma classification is based only on histopathological characterization, and no circulating biomarkers have been identified to predict tumour progression2. Indeed, microRNAs are promising circulating biomarkers because they can be released from tumour cells into the blood stream via exosomes, showing potential to be used as liquid biopsies3. Previously, Cyclin D1 overexpression was suggested as a possible meningioma biomarker as it correlates with proliferative activity and tumour grade, while high levels of Cyclin E1 were shown to correlate with higher recurrence rates4,5. In this study, we showed, for the first time, that the transcription factor GATA-4 is overexpressed in malignant meningioma cells and tissues, controlling the miR-15 family (miR-15a/b-16-497-195) expression. Moreover, we proved that the miR-497~195 cluster not only regulates Cyclin D1-D2-D3 and E1 levels, but it also modulates GATA-4 expression in meningioma. Moreover, we showed that the levels of miR-497~195 cluster are significantly lower in exosomes derived from higher grade meningioma patients’ blood serum, supporting their potential as diagnostic biomarkers.
Clinical Practice Patterns for Hydroxyurea Initiation in Young Children with Sickle Cell Disease
Authors: Anna M Hood, Yolanda Johnson, Cara Nwankwo, Lisa M Shook, Aimee K Hildenbrand, Allison A. King, Kim Smith-Whitley, Sherif M. Badawy, Alexis A Thompson, Susan E Creary, Connie M. Piccone, Lynne D. Neumayr, Jean L. Raphael, Amber M Yates, Sohail Rana, Steven K Reader, Emily Riehm Meier, Amy Sobota, Lori E. Crosby
Journal: Blood (2019)
A Multi-Institutional Validation of the Prognostic and Predictive Value of the Neutrophil-to-Lymphocyte Ratio in Patients with Diffuse Large B- Cell Lymphoma: A Study from the Latin American Working Group for Lymphomas (GELL)
Authors: Denisse A. Castro, Brady E. Beltrán, Luis Villela M, Marialejandra Torres Viera, Victoria Otero, Lorena Fiad, Camila Peña, Henry Idrobo, Christine Rojas, Ivan Perdomo, Pilar León, Karen Lalupu, Sally Rose Paredes, Fernando Pérez-Jacobo, Ana Ramirez-Ibarguen, David Gomez-Almaguer, Jose A Hernández-Hernández, Myrna Candelaria, Guillermo J. Ruiz-Arguelles, Andrés Gómez-De León, Efreen Montaño Figueroa, Melani Otañez, Carlos Best, Luis E Malpica Castillo, Eduardo Sotomayor, Jorge J. Castillo
Journal: Blood (2019)
Outcomes of Patients with T-Lymphoblastic Lymphoma Undergoing Allogeneic Stem Cell Transplantation: Retrospective Results from a Single Center
Authors: Amandeep Salhotra, Liana Nikolaenko, Lu Chen, Ni-Chun Tsai, Diane Lynne Smith, Auayporn P. Nademanee, Leslie L. Popplewell, Alex F. Herrera, Matthew Mei, Ibrahim Aldoss, Vinod A. Pullarkat, Stephen J. Forman, Jasmine M. Zain
Journal: Blood (2019)
Patterns of Relapse and Treatment for Relapsed/Refractory AL Amyloidosis: A Systematic Review
Authors: Adeela Mushtaq, Hamza Hassan, Razwana Khanam, Ahmad Iftikhar, Midhat Lakhani, Muhammad Abdullah Yousaf, Muhaddis Ejaz Ahmad, Maaz Ahmed Yusufi, Seemal Iftikhar, Aneeqa A Zafar, Irbaz Riaz, M Hasib Sidiqi, Faiz Anwer
Journal: Blood (2019)
INNV-38. RATE OF EEG IN GLIOMA PATIENTS: SHOULD THIS BE PART OF STANDARD OF CARE FOR NEW BRAIN TUMOR PATIENTS?
Authors: Wendy Sherman
Journal: Neuro-Oncology (2019)

Abstract Current guidelines recommend antiepileptic drug (AED) therapy for glioma patients only in patients who have experienced a seizure. There is no current recommendation in regards to performing EEG monitoring in glioma patients. Thus, typically only clinical seizures have prompted AED therapy in glioma patients. Our purpose was to investigate the rate of EEG monitoring in glioma patients entered into our glioma registry, along with seizure and AED rates. Using our glioma registry to date, of 167 glioma patients, 119 patients had EEGs performed during their clinical course. Of those 119 patients, 104 glioma patients had either clinical or electrographic seizure activity and all 104 were on AEDs. This observation indicates that baseline eeg monitoring might be considered in all newly diagnosed glioma patients to reduce seizure incidence, potentially, starting AED prophylaxis if epileptiform activity is seen on EEG prior to clinical seizure activity to potentially reduce morbidity and healthcare costs related to clinical seizure activity. This warrants further prospective study.
Diet Quality of Long-Term Allogeneic and Autologous Stem Cell Transplant (HCT) Survivors
Authors: Nosha Farhadfar, Debra Lynch Kelly, Lacey E. Mead, Shalini Nair, Randy A. Brown, John W. Hiemenz, Jack W. Hsu, Hemant S. Murthy, W. Stratford May, John R. Wingard, Wendy J Dahl
Journal: Blood (2019)
Surgical Treatment of Varicose Veins
Authors: H. I. Biegeleisen
Journal: JAMA (1962)

ABSTRACT To the Editor:— I was gratified to read Results of Surgical Treatment of Varicose Veins, by Drs. Agrifoglio and Edwards, in the Dec. 2, 1961, issue of The Journal (178:906). I would like to point out constructively how this long-term surgical study could have greater value. In the interest of brevity, this will be tabulated: (1) Postoperative injection treatment was given to 168 patients within the first year. This is 40% of all the cases studied. Later in the article the authors indicate that injection treatment should not be used because of damage to the valves. How can this point of view be reconciled with the fact that in almost half their cases injections had to be used to complete the cure? (2) There is no mention of heredity as a factor in varicose vein formation, nor is there any admission of chronicity in this disease. Rather, the authors
Alpha-fetoprotein in antenatal diagnosis of neural tube defects
Authors: A. Walling
Journal: BMJ (1977)

incorrectly diagnosed until necropsy and the overall mortality was 25 %.Trapnell5 reported that in 6% of his series of 590 patients with acute pancreatitis the diagnosis was made only at necropsy and the overall series mortality was more than 20 %.Thus in any analysis of mortality in primary acute pancreatitis it is important to differentiate between patients in whom the diagnosis is made at necropsy and those in whom it is made during life.Mr Imrie:' and others' have shown that in trials of various therapeutic regimens there is a mortality of about 1000, but these patients are only those who had the diagnosis made in life.Mortality from acute pancreatitis will always be higher than people think is acceptable clinical practice until we can diagnose all cases in life and undertake appropriate early treatment.This distinction is important and must be fully appreciated and acknowledged when making comparisons between different series.Alas, this distinction is not always appreciated, which may explain some of the confusion about mortality in acute pancreatitis.
Cancer immunotherapy needs to learn how to stick to its guns
Authors: Asmi Chakraborty, Charles J. Dimitroff
Journal: Journal of Clinical Investigation (2019)

Cancer immunotherapy and its budding effectiveness at improving patient outcomes has revitalized our hope to fight cancer in a logical and safe manner. Immunotherapeutic approaches to reengage the immune system have largely focused on reversing immune checkpoint inhibitor pathways, which suppress the antitumor response. Although these approaches have generated much excitement, they still lack absolute success. Interestingly, newly described host-tumor sugar chains (glycosylations) and glycosylation-binding proteins (lectins) play key roles in evading the immune system to determine cancer progression. In this issue of the JCI, Nambiar et al. used patient head and neck tumors and a mouse model system to investigate the role of galactose-binding lectin 1 (Gal1) in immunotherapy resistance. The authors demonstrated that Gal1 can affect immune checkpoint inhibitor therapy by increasing immune checkpoint molecules and immunosuppressive signaling in the tumor. Notably, these results suggest that targeting a tumor's glycobiological state will improve treatment efficacy.
Personal Use of Drug Samples by Physicians and Office Staff
Authors: Lewis H. Margolis
Journal: JAMA (1997)

To the Editor.  —Dr Westfall and colleagues 1 seem to be in an unnecessary quandary over the ethical implications of the personal use of drug samples by physicians. The practice is unethical because it violates at least 3 duties of physicians. 2 The duty to do no harm— primum non nocere —is violated because samples raise the cost of care to patients, in that samples generate cost, ultimately paid for by patients, beyond the accepted cost of research, production, and marketing. Presumably patients have other uses for the resources that pay for physician samples. Another possible harm is through the possible improper use of medicines, as suggested by Westfall et al. The duty of fidelity—the obligation to serve the interests of the patient—is transgressed because the acceptance of samples for personal use makes the physician an agent of the pharmaceutical companies that provide them. The conflict of interest between serving
Activation of Regulatory T Cells with IL-2 and TNF-α to Promote Homing to the Gut and to Improve Acute GvHD Prevention
Authors: Antonella Mancusi, Samanta Bonato, Rachele Del Sordo, Sara Piccinelli, Eni Hoxha, Tiziana Zei, Roberta Iacucci Ostini, Franca Falzetti, Alessandra Carotti, Loredana Ruggeri, Michele Giansanti, Robert S. Negrin, Massimo Fabrizio Martelli, Andrea Velardi, Antonio Pierini
Journal: Blood (2019)
Quality of Life (QoL) in Patients With Relapsed/Refractory Non-Hodgkin Lymphoma (NHL) Treated with Polatuzumab Vedotin Plus Rituximab in the ROMULUS Study
Authors: Per-Olof Thuresson, Brittany Gentile, David Ramies, Aino Launonen, Franck Morschhauser
Journal: Blood (2019)
Influence of Bone Marrow Stromal and Leukemic Cells on Cytarabine Chemo-Toxicity in Acute Myeloid Leukemia (AML)
Authors: Liana E Gynn, Elizabeth Anderson, Gareth M Robinson, Sarah Anne Wexler, Gillian Upstill-Goddard, Christine Cox, Rhys Gareth Morgan, Jennifer E May
Journal: Blood (2019)
EPID-26. SEX-SPECIFIC GLIOMA MOLECULAR SIGNATURES
Authors: Elizabeth Claus, Vincent Cannataro, Stephen Gaffney, Jeffrey Townsend
Journal: Neuro-Oncology (2019)

Abstract Many genetic and environmental factors have been explored in epidemiological studies of glioma risk but the magnitude of effect of these factors on gliomagenesis is uncertain. A number of constitutional genes associated with glioma risk, many noted to be related to telomere function, have been identified. High-dose ionizing radiation has consistently been associated with an increased glioma risk while a history of allergies and atopy is inversely associated with risk. Results have been inconsistent for most other factors studied but whether this lack of evidence is due to study limitations or a true lack of risk factors is unclear. Using 901 glioma exomes from The Cancer Genome Atlas (TCGA) we estimate the intensity of positive selection on gene variants, and order them by their cancer effect size, quantifying the contribution of gene variants to the somatic evolution of glioma. Examination of subsets of tumor exomes from males and females showed similar patterns in genes mutated but some differences in variant profile for a given gene including PIK3CA suggesting a possible differential response to treatment. Furthermore, these cancer effect sizes enable quantification of the degree to which COSMIC-defined processes associated with genetic pathways and environmental environmental factors within the somatic evolution of tumors contribute mutations that are highly selected, driving gliomagenesis. The results confirm the major roles of previously reported mutations in IDH1, TP53, EGFR, and PIK3CA, but also suggest a large cancer effect for low-prevalence genes including BRAF. Age-related mutagenesis was the primary molecular signature identified for all glioma while homologous recombination disfunction was an important signature for males but not females. Although additional signatures remain to be identified and less common exposures difficult to access, these data suggest a profile of glioma mutations that are caused primarily from endogenous rather than exogenous factors.
Twist1-Induced Epithelial Dissemination Requires Prkd1 Signaling
Authors: Dan Georgess, Veena Padmanaban, Orit Katarina Sirka, Kester Coutinho, Alex Choi, Gabriela Frid, Neil M. Neumann, Takanari Inoue, Andrew J. Ewald
Journal: Cancer Research (2019)

Abstract Dissemination is an essential early step in metastasis but its molecular basis remains incompletely understood. To define the essential targetable effectors of this process, we developed a 3D mammary epithelial culture model, in which dissemination is induced by overexpression of the transcription factor Twist1. Transcriptomic analysis and ChIP-PCR together demonstrated that protein kinase D1 (Prkd1) is a direct transcriptional target of Twist1 and is not expressed in the normal mammary epithelium. Pharmacologic and genetic inhibition of Prkd1 in the Twist1-induced dissemination model demonstrated that Prkd1 was required for cells to initiate extracellular matrix (ECM)–directed protrusions, release from the epithelium, and migrate through the ECM. Antibody-based protein profiling revealed that Prkd1 induced broad phosphorylation changes, including an inactivating phosphorylation of β-catenin and two microtubule depolymerizing phosphorylations of Tau, potentially explaining the release of cell–cell contacts and persistent activation of Prkd1. In patients with breast cancer, TWIST1 and PRKD1 expression correlated with metastatic recurrence, particularly in basal breast cancer. Prkd1 knockdown was sufficient to block dissemination of both murine and human mammary tumor organoids. Finally, Prkd1 knockdown in vivo blocked primary tumor invasion and distant metastasis in a mouse model of basal breast cancer. Collectively, these data identify Prkd1 as a novel and targetable signaling node downstream of Twist1 that is required for epithelial invasion and dissemination. Significance: Twist1 is a known regulator of metastatic cell behaviors but not directly targetable. This study provides a molecular explanation for how Twist1-induced dissemination works and demonstrates that it can be targeted.
MNGI-01. A PHASE 0 TRIAL OF RIBOCICLIB IN AGGRESSIVE MENINGIOMA PATIENTS INCORPORATING A TUMOR PHARMACODYNAMIC- AND PHARMACOKINETIC-GUIDED EXPANSION COHORT
Authors: An-Chi Tien, Jing Li, Xun Bao, Alanna DeRogatis, Yoko Fujita, Chelsea Pennington-Krygier, Seongho Kim, Shwetal Mehta, Nader Sanai
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND New approaches are urgently needed for aggressive meningiomas, which remain largely incurable. Forkhead Box M1 (FOXM1) has been identified as a master transcription factor in aggressive meningiomas and Cyclin D-dependent Kinases (CDK) are positive regulators of cell-cycle entry, promoting tumorigenesis through FOXM1 activation. We evaluated the tumor pharmacokinetics (PK), tumor pharmacodynamics (PD), and preliminary clinical response of ribociclib, a selective CDK4/6-inhibitor, in aggressive meningioma patients. METHODS Eight aggressive WHO Grade II/III meningioma patients with intact RB expression were enrolled and administered oral ribociclib daily for 5 days prior to tumor resection. Plasma, tumor, and cerebrospinal fluid (CSF) samples were collected at 2, 8, or 24 h after the last dose. Total and unbound drug concentrations were determined using a validated LC-MS/MS method. PD effects, including RB and FoxM1 phosphorylation, were compared to matched archival tissue. Patients with PK and PD responses in tumor tissue, defined as unbound ribociclib concentration &gt; 5-fold in vitro IC50 (0.04µM) and &gt;20% decrease in pRB levels, respectively, were enrolled into an expansion cohort for preliminary assessment of progression-free survival. RESULTS The median CSF concentration of ribociclib was 0.25 µM. In tumor tissue, the median unbound ribociclib concentration was 1.36 µM and the median unbound tumor-to-plasma ratio was 5.34. Suppression of G1-to-S phase was inferred in tumors with declining FoxM1 phosphorylation (50%), RB phosphorylation (38%), and cellular proliferation (75%). Four patients demonstrated concurrent PK and PD responses and were graduated to continuous ribociclib therapy. At 14 months, two of these patients (one Grade II and one Grade III) demonstrate partial responses per RANO criteria. CONCLUSION Ribociclib achieves pharmacologically-active concentrations in aggressive meningioma tissue. Target modulation was demonstrated by a decrease in FOXM1-mediated tumor proliferation. Further investigation of ribociclib as a therapeutic strategy for aggressive meningiomas is warranted.
Identifying Cytokine Biomarkers of Response to Pegylated-Interferon Therapy in Polycythemia Vera and Essential Thrombocythemia: Correlative Analysis from the MPN-RC 111/112 Trials
Authors: Andrew Dunbar, Heidi E. Kosiorek, Aishwarya Krishnan, Erin McGovern, Young Park, Minal A Patel, Rona Singer Weinberg, Abdulraheem Yacoub, Amylou C. Dueck, John Mascarenhas, Ross L. Levine, Ronald Hoffman, Raajit K. Rampal
Journal: Blood (2019)
Efficacy and Safety of Ixazomib-Dexamethasone, Ixazomib-Cyclophosphamide-Dexamethasone, Ixazomib-Thalidomide-Dexamethasone and Ixazomib-Bendamustine-Dexamethasone for Elderly Newly Diagnosed Multiple Myeloma (NDMM) Patients: Analysis of the Phase II Randomized Unito-EMN10 Study
Authors: Alessandra Larocca, Paolo Corradini, Roberto Mina, Nicola Cascavilla, Anna Marina Liberati, Norbert Pescosta, Maria Teresa Petrucci, Giovannino Ciccone, Andrea Capra, Francesca Patriarca, Delia Rota Scalabrini, Vanessa Innao, Marco Poggiu, Michele Cea, Renato Zambello, Anna Baraldi, Angelo Belotti, Claudia Cellini, Monica Galli, Mariella Grasso, Sara Aquino, Gloria Margiotta Casaluci, Giovanni De Sabbata, Stelvio Ballanti, Massimo Offidani, Katia Mancuso, Mario Boccadoro, Sara Bringhen
Journal: Blood (2019)
Congenital Mitral Stenosis
Authors: CHARLOTTE FERENCZ, ARNOLD L. JOHNSON, F. W. WIGLESWORTH
Journal: Circulation (1954)

Nine cases of congenital mitral stenosis are presented, with a review of 34 cases from the literature. A high incidence of associated malformations of the aortic valve, the aorta and the ductus arteriosus is apparent. Clinical findings and results of investigative procedures have been reviewed. Mitral stenosis is responsible for severe circulatory alterations and the development of hypertensive pulmonary vascular changes. This malformation has serious consequences. It is associated with early mortality and renders ineffective the surgical repair of associated coarctation of the aorta or patent ductus arteriosus.