tbuckley/cabot-search huggingface dataset:
ATIM-46. A MULTICENTER, PHASE I, TRIAL OF RADIATION, TEMOZOLOMIDE AND RRx-001 FOLLOWED BY MAINTENANCE TEMOZOLOMIDE WITH OR WITHOUT RRx-001 IN NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS
Authors: Robert Aiken, Howard Fine, Nicholas Butowski
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND RRx-001 is an aerospace-derived radiochemosensitizer with minimal toxicity. The purpose of this trial was to establish the safety of RRx-001 plus radiotherapy and temozolomide and to look for signals of enhanced anti-tumor activity in patients with newly diagnosed glioblastoma. METHODS In this non-randomized trial called G-FORCE-1 (NCT02871843), 18 newly diagnosed, histologically verified glioblastoma patients were enrolled. The treatment plan included 6 weeks of temozolomide and radiotherapy with RRx-001 followed by maintenance temozolomide with or without RRx-001. Four cohorts of 3 patients received intravenous RRx-001 at doses of 0.5,1,2, or 4 mg/week during radiotherapy only. An additional two cohorts of 3 patients received 4 mg/week of RRx-001 during radiotherapy and 0.5 mg/week of RRx-001 during temozolomide maintenance. RESULTS There were no grade 3 or 4 dose-limiting toxicity events (DLT) that appeared related to RRx-001 for the dose range of 0.5 to 4 mg/week. A maximum tolerated dose was not defined. The main adverse event related to RRx-001 was injection-site reaction. The overall response rate was 16.7% (3 PR out of 18) pending confirmation since pseudoprogression was prevalent, and the disease control rate was 61.1% (3 PR, 8 SD out of 18). The median time to tumor progression (95% confidence interval lower limit of 9.2 months to NR) and the median overall survival time (95% confidence interval lower limit of 12.9 months to NR) have not been reached after a median follow-up time of 10.3 months (range: 2.7 to 25 months.). CONCLUSION RRx-001 was well tolerated with concurrent temozolomide and radiotherapy and with temozolomide maintenance in 18 newly diagnosed glioblastoma patients. The primary objective to determine the MTD of RRx-001 was not met, since no DLTs occurred. The median time to progression and overall survival time have not been met after a median follow up time of 10.3 months.
Platelet FcγRIIA Signaling Results in Ubiquitination and Cellular Translocation of Activated Syk
Authors: Shaji Abraham, Leonard C. Edelstein, Chad A Shaw, Pierrette Andre, Xianguo Kong, Carol T Dangelmaier, Alexander Tsygankov, Paul F Bray, Satya P. Kunapuli, Steven E. McKenzie
Journal: Blood (2014)
Time to Change Our Practice: Experience in the Treatment of Steroid Refractory Graft Versus Host Disease in a Universitary Hospital in Chile
Authors: Nicolas Triantafilo, Mauricio Sarmiento Maldonado, Felipe Palacios, James Campbell, Vicente Sandoval, Andres Rojas, Jara Veronica, Soto Katherine, Silvana Arellano, Carla Lorca, Isabel Pizarro, Elizabeth Rivera, Mauricio Galleguillos, Isabel Rodriguez, Pablo Bertin, Mauricio Ocqueteau, Jaime Pereira
Journal: Blood (2019)
CBMT-39. TARGETING METABOLIC PATHWAYS IN HYPOXIA FOR GLIOBLASTOMA
Authors: Aleksandra Gruslova, Alessia Lodi, Mengxing Li, Mei Zhou, Michael Garcia, Stefano Tiziani, Andrew Brenner, Laura Caflisch
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Metabolic adaptation to hypoxia is a crucial consideration in combating anti-angiogenic resistance. We previously explored the potential of targeting the peroxisomal fatty acid oxidation (FAO) pathway and observed higher potency to peroxisomal FAO inhibitor thioridazine in hypoxia in vitro. In this study we further examine the effects of peroxisomal FAO enzyme ACOX1, looking at differences in mitochondrial and peroxisomal FAO in hypoxia between subtypes, and explore additional metabolic pathways that can be potentially further studied. METHODS We utilized a CRISPR doxycycline-inducible U251 knockout cell line for the peroxisomal FAO gene ACOX1 and examined growth and viability in 2 weeks hypoxia (2% O2). We analyzed the gene expression of 13 peroxisomal and mitochondrial FAO enzymes in six different patient-derived cell lines. Finally, we characterized serum metabolites that are associated with tumor hypoxic volume, progression-free survival, and overall survival in patients undergoing clinical trial for TH302 and bevacizumab with bevacizumab refractory tumors. RESULTS We observed decreased cell growth and viability (p &lt; .03) specifically in hypoxia but not normoxia with ACOX1 knock out. We saw some changes in gene expression (|ΔΔCt| &gt;1) in hypoxia for all genes, which differed between cell lines. ACOX1 and CPT1A expression were strongly decreased (|ΔΔCt| &gt;2) while ACADSB expression was strongly increased for the proneural cell line. ACOX1 expression was strongly decreased in our most thioridazine-sensitive cell line. ACOX2, ACADVL, CPT1A, CPT1C, and DECR2 expression were strongly increased in one of the proneural cell lines. Twelve polar metabolites were positively or negatively correlated (|r| &gt;.4) with both hypoxic volume and either overall survival or progression-free survival. CONCLUSION Peroxisomal FAO and other metabolic pathways may be essential to target in order combat metabolic resistance during anti-angiogenic therapy. Better understanding differences in metabolism in different tumor environments will help determine which targets will be most therapeutically useful.
NK CD56brightCD16neg reconstitution over Time (NK56-index) Significantly Impacts Long Term Outcome in Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Dante Escorcio-Tavares, Vinicius Campos de Molla, Elisa Y Kimura, Vergilio Colturato, Maura V Ikoma, Victor Gottardello Zecchin, Adriana Seber, Nelson Hamerschlak, Vanderson Rocha, Yana Novis, Mihoko Yamamoto, Marcio Nucci, Celso Arrais-Rodrigues, Matheus Vescovi Gonçalves
Journal: Blood (2019)
David Oliver: Does doctors’ admin take up too much time?
Authors: David Oliver
Journal: BMJ (2019)

An essay by Atul Gawande in the New Yorker , “Why doctors hate their computers,” made me reflect on the growing burden of administrative tasks doctors face at the expense of patient care, personal development, and their lives outside work.1

When I started as a hospital consultant 22 years ago, hospital email had only just begun. Now, a week’s holiday means several hundred messages on my return. Many need no action or refer to issues already resolved, but plenty need careful reading or a reply. And replying to emails with many recipients begets more emails.

Remote working and emailing outside working hours intensify the pressure, if we feel forced to keep checking emails. Not …
Efficacy and Safety of Fully Human Bcma CAR T Cells in Combination with a Gamma Secretase Inhibitor to Increase Bcma Surface Expression in Patients with Relapsed or Refractory Multiple Myeloma
Authors: Andrew J. Cowan, Margot Pont, Blythe Duke Sather, Cameron J. Turtle, Brian G. Till, Anne M Nagengast, Edward N. Libby, Pamela S. Becker, David G. Coffey, Sherilyn A. Tuazon, Brent L Wood, Michelle L Blake, Melissa G Works, Ted A Gooley, Qian Vicky Wu, David G. Maloney, Stanley R. Riddell, Damian J. Green
Journal: Blood (2019)
PET-Adapted Nivolumab or Nivolumab Plus ICE As First Salvage Therapy in Relapsed or Refractory Hodgkin Lymphoma
Authors: Alex F. Herrera, Robert W. Chen, Joycelynne Palmer, Ni-Chun Tsai, Matthew Mei, Leslie L. Popplewell, Auayporn P. Nademanee, Liana Nikolaenko, Kathryn McBride, Ricardo Ortega, Joo Y. Song, Steven Rosen, Larry W Kwak, Stephen J Forman, Hun Ju Lee
Journal: Blood (2019)
NIMG-77. RESPONSE ASSESSMENT USING MULTIPARAMETRIC MRI DURING CHEMORADIATION PREDICTS OVERALL SURVIVAL IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Michelle Kim, Madhava Aryal, Hemant Parmar, Pin Li, Matthew Schipper, Daniel Wahl, Theodore Lawrence, Yue Cao
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Identifying both aggressive hypercellular (HCV) and hyperperfused (hCBV) regions of glioblastoma (GBM) prior to radiation (RT) using multiparametric MRI (mpMRI) predicts PFS and recurrence better than either technique alone, and is under investigation in a phase II trial as a novel target for dose-intensified RT. We hypothesized that early response in combined HCV/hCBV could be assessed using mpMRI and predict OS better than baseline assessment. METHODS Forty-three patients with newly diagnosed GBM underwent prospective high b-value (b=3000 s/mm2) DW-MRI and DCE-MRI pre-RT and 3 weeks into RT. Twenty patients were treated on a dose-escalation trial specifically targeting HCV/hCBV identified by mpMRI. An automated threshold method was used to generate HCV (mean contralateral normal brain+2SD) and hCBV (contralateral normal frontal grey matter+1SD). Survival was calculated using Kaplan-Meier method and compared using log-rank test. Age, gender, performance status, RT dose, extent of surgery, MGMT methylation, and imaging characteristic were tested in Cox proportional hazards models for survival. RESULTS Most patients had gross total (47%) or subtotal resection (37%), and 25% were MGMT methylated. Significant volumetric reduction during RT was observed in the Gd-enhanced volume (4.4 cc reduction, 95%CI 1.1–7.7, 17%), as well as HCV (1.8 cc reduction, 95%CI 0.2–3.4, 19%) and hCBV (1.1 cc reduction, 95%CI -0.4–2.6, 10%). No difference was observed between MGMT subgroups, but patients treated on protocol specifically targeting the mpMRI volume had significant reduction in combined HCV/hCBV (-4.4 cc, 95%CI -6.6,-2.3) vs non-protocol patients (-0.3 cc, 95%CI -2.6,2.0, p=0.006). A reduction in combined HCV/hCBV was associated with superior OS (AHR 0.60, 95%CI 0.40–0.89, p=0.01), while baseline imaging (all p&lt; 0.90) and change in Gd-enhanced volume (p=0.61) were not. CONCLUSIONS Significant early response in HCV/hCBV during treatment is observed when targeted with dose-intensified RT, and is associated with improved OS with potential for adaptive strategies in future trials.
Igcaller: Reconstructing the Rearranged Immunoglobulin Gene in Lymphoid Neoplasms from Whole-Genome Sequencing Data
Authors: Ferran Nadeu, Rut Mas-de-les-Valls, Romina Royo, Alba Navarro, Sílvia Beà, Junyan Lu, Alfredo Rivas-Delgado, Neus Villamor, Silvia Martín, Marta Aymerich, Tycho Baumann, Julio Delgado, Dolors Colomer, Xose S Puente, Thorsten Zenz, Peter J Campbell, Francesco Maura, Elias Campo
Journal: Blood (2019)
Association Between Resident Physician Training Experience and Program-Level Performance on Board Examinations
Authors: Ryan J. Ellis, Yue-Yung Hu, Andrew T. Jones, Jason P. Kopp, Nathaniel J. Soper, David B. Hoyt, Jo Buyske
Journal: JAMA Surgery (2019)

The American Board of Surgery (ABS) certification requires that candidates pass 2 examinations: the qualifying examination and the certifying examination.While success on
Glutamine Depletion By Addicted Myeloma Cells Inhibits Osteoblastic Differentiation of Bone Marrow Mesenchymal Stromal Cells Limiting Asparagine Availability: A Possible New Mechanism for Myeloma Bone Disease
Authors: Martina Chiu, Denise Toscani, Emanuela Vicario, Roberta Andreoli, Giuseppe Taurino, Valentina Marchica, Paola Storti, Massimiliano Bianchi, Ovidio Bussolati, Nicola Giuliani
Journal: Blood (2019)
Distinct Polysaccharide Utilization Profiles of Human Intestinal Prevotella copri Isolates
Authors: Hannah Fehlner-Peach, Cara Magnabosco, Varsha Raghavan, Jose U. Scher, Adrian Tett, Laura M. Cox, Claire Gottsegen, Aaron Watters, John D. Wiltshire-Gordon, Nicola Segata, Richard Bonneau, Dan R. Littman
Journal: Cell Host & Microbe (2019)
Deep learning predicts function of live retinal pigment epithelium from quantitative microscopy
Authors: Nicholas J. Schaub, Nathan A. Hotaling, Petre Manescu, Sarala Padi, Qin Wan, Ruchi Sharma, Aman George, Joe Chalfoun, Mylene Simon, Mohamed Ouladi, Carl G. Simon, Peter Bajcsy, Kapil Bharti
Journal: Journal of Clinical Investigation (2019)

Increases in the number of cell therapies in the preclinical and clinical phases have prompted the need for reliable and noninvasive assays to validate transplant function in clinical biomanufacturing. We developed a robust characterization methodology composed of quantitative bright-field absorbance microscopy (QBAM) and deep neural networks (DNNs) to noninvasively predict tissue function and cellular donor identity. The methodology was validated using clinical-grade induced pluripotent stem cell–derived retinal pigment epithelial cells (iPSC-RPE). QBAM images of iPSC-RPE were used to train DNNs that predicted iPSC-RPE monolayer transepithelial resistance, predicted polarized vascular endothelial growth factor (VEGF) secretion, and matched iPSC-RPE monolayers to the stem cell donors. DNN predictions were supplemented with traditional machine-learning algorithms that identified shape and texture features of single cells that were used to predict tissue function and iPSC donor identity. These results demonstrate noninvasive cell therapy characterization can be achieved with QBAM and machine learning.
Therapeutic Plasma Exchange in Pediatrics for Immunologic Disorders; Tolerated and Safe Process for Pediatric Life-Threatening Conditions
Authors: Jean-Sebastien Diana, Sandra Manceau, Tioka Rabeony, Caroline Elie, anne-Marine Lenzotti, Valerie Jolaine, Mélodie Aubart, Nadège Salvi, Christine Bodemer, Brigitte Bader-Meunier, Christine Barnerias, Franck Iserin, Christophe Chardot, Florence Lacaille, Sylvain Renolleau, Isabelle Desguerre, Rémi Salomon, Laure Joseph, Francois Lefrère, Marina Cavazzana, Laurent Dupic, Marianne Delville
Journal: Blood (2019)
Termination of pregnancy.
Authors: P Moxon
Journal: BMJ (1972)

There is, however, a much more sinister aspect to this brainwashing Drocess by the new media and by noise affecting young people, and that is loss of critical faculties and increased suggestibility.These two phenomena are well known to psychiatrists and may play their part in the various violent protest movements we are witnessing to-day.We have created a society where for some young people stimulation of the mind by the mass media and by other undesirable aspects of our society, such as many films, comics, loud pop music, noise at work, and traffic has already reached sat- uration point, and the cult of drug addiction may be one wav of escape for them.It is high time our Doliticians and social scientists recognized these facts, as a re- versal of the trend at this stage will prove very difficult.-Iam, etc.
CSIG-11. CENTRAL NERVOUS SYSTEM TUMOR PATIENTS HAVE ELEVATED LEVELS OF CIRCULATING EXTRACELLULAR VESICLES
Authors: Franz Ricklefs, Cecile Maire, Katharina Kolbe, Mareike Holz, Rudolph Reimer, Markus Glatzel, Ennio Chiocca, Manfred Westphal, Katrin Lamszus
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND We previously demonstrated that extracellular vesicles (EV) from CNS tumors reflect the molecular subtype of the original tumor and mediate an exchange of pro-oncogenic signals. EVs are commonly characterized by nanoparticle analysis (NTA), electron microscopy and tetraspanin markers, including CD9, CD81 and CD63. It is unclear, however, to what extent circulating tumor EVs are utilizable for diagnostic purposes and how their marker profile overlaps with EVs derived from other cell types. Aiming to define markers that allow distinction and enrichment of glioma EVs from patient blood, we utilized Imaging Flow Cytometry (IFC) to discriminate single EVs via multiple surface markers. METHODS EVs were isolated from blood of patients suffering from glioblastoma (n=24), anaplastic astrocytoma (n=8), brain metastasis (n=7), meningioma (n=12), pituitary gland tumor (n=11), epilepsy (n=11) and from healthy controls (n=18) and were analyzed by IFC, immunoblotting, electron microscopy and NTA. In addition, circulating EVs from PALM-GFP-GL261 and PALM-GFP-CT2A tumor-bearing mice (n=5) as well as from glioblastoma stem-like (GSC) cultures (n=4), neural stem cells (NSC), cerebral endothelial cells (cEC) and T-cells (n=4) were characterized. RESULTS CNS tumor patients have significantly elevated levels of circulating EVs (P &lt; 0.001), as measured by NTA and IFC. In particular, the proportion of double positive CD9+/CD81+, CD9+/CD63+and CD63+/CD81+EVs is increased in glioblastoma patients (p=0.018) compared with healthy controls[L1]. In accordance, cultured GSCs secrete increased levels of CD9+/CD81+EVs in vitro. In the two syngeneic murine PALM-GFP glioma models, only 0.1-0.01% of circulating plasma EVs were found to be derived from intracranial tumors, underlining the need to identify markers that can enrich tumor-specific EVs for molecular profiling. CONCLUSION Glioma patients display increased levels of circulating plasma EVs that can be profiled by IFC, which is a unique and novel technique that facilitates discrimination of different EV subpopulations.
Comparison of RNA-Based Versus DNA-Based Quantitative KIT D816V Mutation Analysis Reveals Significant Disparity in Patients with Advanced Systemic Mastocytosis
Authors: Mohamad Jawhar, Nicole Naumann, Johannes Lübke, Juliana Schwaab, Oliver Hofmann, Thomas Kielsgaard Kristensen, Karl Sotlar, Verena Haselmann, Sven Schneider, Georgia Metzgeroth, Henning D. Popp, Alice Fabarius, Peter Bugert, Wolf-Karsten Hofmann, Andreas Reiter
Journal: Blood (2019)
Sustained release of antimicrobials from double-layer nanofiber mats for local treatment of periodontal disease, evaluated using a new micro flow-through apparatus
Authors: Špela Zupančič, Luca Casula, Tomaž Rijavec, Aleš Lapanje, Matevž Luštrik, Anna Maria Fadda, Petra Kocbek, Julijana Kristl
Journal: Journal of Controlled Release (2019)
Tuberculosis in the Elderly
Authors: J. E. Geddes
Journal: BMJ (1963)

picture) responding to riboflavin had also marked ataxia with loss of co-ordination, light touch, and vibration sense in the legs.All the skin and mucous membrane changes rapidly cleared, but despite intensive B-complex vitamin therapy the neurological signs remained with neither amelioration nor deterioration for at least three years after the original admission.Money's three cases in Kampala2 of " obscure funicular myelopathy " had certain features in common with those now reported.Diminished visual acuity in the absence of optic disk changes, unaffected by thiamine or riboflavin but apparently responding dramatically to vitamin B12 injections (50 micrograms daily for one week), was reported3 in three patients at Mwanza with no other neurological signs.Investigation of future cases should include closer examination of the diet, therapeutic trial with specific vitamins of the B complex, examination for scotomata, contraction of the visual fields, measurement of vitamin B12 in the blood, and riboflavin, thiamine, and N'methylnicotinamide in the urine.-Iam, etc.,
Absence of Coronary Artery Calcification in Middle-Aged Familial Hypercholesterolemia Patients Without Atherosclerotic Cardiovascular Disease
Authors: Reed Mszar, Gowtham R. Grandhi, Javier Valero-Elizondo, Salim S. Virani, Ron Blankstein, Michael Blaha, Pedro Mata, Marcio H. Miname, Khalid Al Rasadi, Harlan M. Krumholz, Raul D. Santos, Khurram Nasir
Journal: JACC. Cardiovascular imaging (2019)
ATG5 Dependent Autophagy in Graft-Versus-Host Disease Target Organs Mitigates Disease Severity Post Allogeneic Bone Marrow Transplant
Authors: Austin Taylor, Kay Oravecz-Wilson, Hideaki Fujiwara, Stephanie Kim, Dan Peltier, Molly Radosevich, Yaping Sun, Pavan Reddy
Journal: Blood (2019)
EPID-25. HOW MANY PATIENTS IN A REAL WORLD GLIOBLASTOMA POPULATION MEET ELIGIBILITY CRITERIA IN CLINICAL TRIALS?
Authors: Erlend Skaga, Marthe Andrea Skretteberg, Tom Børge Johannesen, Petter Brandal, Einar Osland Vik-Mo, Eirik Helseth, Iver Arne Langmoen
Journal: Neuro-Oncology (2019)

Abstract In population series of glioblastoma (GBM) the median survival is &lt; 1 year. For patients eligible for combined oncological treatment (surgery, radiotherapy (RT) and temozolomide (TMZ)) the median survival raises to 15 months. These patients are younger, have higher performance status and less comorbidity compared to the total GBM population. The extent of selection bias of GBM patients enrolled in clinical trials is, however, unclear. Using the Cancer Registry of Norway and the Brain Tumor Database of Oslo University Hospital, all patients diagnosed with GBM between 2012 and 2016 within a defined geographical area that received all oncological treatment at Oslo University Hospital were identified. Their hospital charts were retrospectively investigated and all patients were evaluated for the possibility to be included in clinical trials according to standard criteria from recent published phase 3 studies. We defined three time points for possible enrollment in trials: before-, halfway through-, and after concomitant RT/TMZ. We identified 424 patients of whom 26 (6.1%) did not undergo surgery. The median survival in the population was 11.7 months. Of the patients that underwent surgery (biopsy or resection), the median survival progressively increased with additional oncological treatment; no RT/TMZ 1.1 months, only RT 7.9 months, RT/TMZ 13.9 months. A potential study patient group≥18 years undergoing surgery for a supratentorial GBM with ECOG ≤2, with normal bone marrow, hepatic and renal function and no severe comorbidity or oncological disease constituted 54% of the population before start of RT/TMZ. Patients adhering to RT/TMZ-treatment and without tumor progression represented 46% and 43% of the population halfway through- and after concomitant RT/TMZ, respectively. The survival of patients that could be included in clinical trials was significantly higher (p&lt; 0.001) than patients not fulfilling standard criteria. Our data suggest a significant patient selection in clinical trials from a real-world GBM population.
Harrison's Grooves
Authors: R. Good
Journal: BMJ (1948)

less severely.Clearly muscular tenseness from anxiety or any other cause will augment pain."From the foregoing it is contended that pain felt in labour is a physiological response to uterine ischaemia, cervical dilata- tion, and stretching of the passages.As in pain from other sources, percention may be modified by the emotional state, which is doubly important in that it may influence actual uterine functioning.While therefore certain obstetricians are able to conduct relatively painless childbirth without anaesthe- sia, this is a tribute to their enthusiasm, personality, skill, and zeal rather than a proof that childbirth is " normally" free from pain.The great majority of parturient women will con- tinue to require some form of analgesia, local or general, and no vague philosophical concepts should be allowed to interfere with progress in this direction.-Iam, etc., London.W.2.
Rate of Sickle Hemoglobin Recovery in Sickle Cell Disease Patients Undergoing Red Blood Cell (RBC) Exchange Transfusion Is Associated with Age of Patients and Number of RBC Units Transfused
Authors: John Chinawaeze Aneke, Aliraza Rajabali, Nafanta Fadiga, Stéphanie Forté, George A. Tomlinson, Christine M. Cserti-Gazdewich, Christopher J. Patriquin, Richard Ward, Jacob Pendergrast, David Barth, Kevin H. M. Kuo
Journal: Blood (2019)