tbuckley/cabot-search huggingface dataset:
Immunization against whooping-cough.
Authors: J. H. Baines
Journal: BMJ (1965)

JOURNAII agree with Dr. Todd that aspirin may well have been a proper drug to prescribe for the " subjects " that he questioned.He tells us that, as a profession, our fault is not the failure to give treatment, but the giving of too much treatment." Steroids, chloroquine, gold, and phenylbutazone are all dangerous drugs which should be reserved for the severely afflicted but which are too often given to patients with minor diseases who 'demand' that something be done."If treatment means just the prescription of drugs he has a case, but every experienced family doctor and many consultants know that proper advice is advice proper to the individual patient, and that the prescription of drugs forms only a small part of the manage- ment of the patient.When we see an out- patient for the first time, we do not know if this patient is suffering from " a minor disease," or will in five years' time be " severely afflicted " and be suitable for treat- ment with " dangerous drugs "-a stage at which these drugs may be dangerous but will almost certainly be ineffectual in preventing disability.Complications usually arise because these drugs are given in unnecessarily large doses and for too long a period of time.If the doctor, before prescribing, listens carefully to what his patients tell him, he will realize that in many of his patients the dominant complaint is not the morning stiffness, pain, and joint swelling, which are accepted as characteristic of early rheumatoid arthritis, but anxiety, frustration, and a fear of crippling which are common early manifesta- tions of this disease and can be relieved by sympathy and willingness to understand the patient and his problem, accompanied some- times by a prescription for one or two aspirin.
Pre-Transplant Use of Tyrosine Kinase Inhibitors Increases Risk of Transplant Associated Thrombotic Microangiopathy - a Single Centre Analysis of Incidence, Risk Factors and Outcomes
Authors: Siddhesh Arun Kalantri, Akanksha Chichra, Amit Kumar Agrawal, Lingaraj Nayak, Avinash Bonda, Sachin Punatar, Anant Gokarn, Bhausaheb Bagal, Libin J Mathew, Sadhana Kannan, Navin Khattry
Journal: Blood (2019)
SIRT7 couples light-driven body temperature cues to hepatic circadian phase coherence and gluconeogenesis
Authors: Zuojun Liu, Minxian Qian, Xiaolong Tang, Wenjing Hu, Shimin Sun, Guo Li, Shuju Zhang, Fanbiao Meng, Xinyue Cao, Jie Sun, Cheng Xu, Bing Tan, Qiuxiang Pang, Bosheng Zhao, Zimei Wang, Youfei Guan, Xiongzhong Ruan, Baohua Liu
Journal: Nature Metabolism (2019)
Diagnosis of Amphetamine Addiction
Authors: P. G. M. G. Walker
Journal: BMJ (1965)

MEDICALJONAintermittently.The immediate cause of death was heart failure, although the clinical symptoms suggested overdosage of one or other of the antidepressant drugs.Analysis showed no evidence of overdosage, and the conclusion that the combined drugs taken in substantially normal dosages had produced these symptoms and contributed to her death seems a more reasonable explanation than that put forward by Dr. Sargant.Surely such a patient can be hypersensitive to the newly introduced drug (desipramine) in com- bination with the drug (phenelzine) which she has tolerated for so long.With all due respect to Dr. Sargant, the fact that pre- viously she had shown no adverse reaction to a different drug (amitriptyline) in com- bination with phenelzine seems irrelevant to me.It may well be that cases like this are extremely infrequent, but need one therefore deny that a small risk exists ?If the prob- able benefit to the patient is greatly in excess of the small risk, then experienced psychiatrists like Dr. Sargant are presumably justified in using this line of treatment without fear of litigation.Those with less specialized experience in using antidepressant drugs will probably prefer to heed the warnings of the Witts Committee and other authorities.One such authority, Dr. Hollister, writing on " The Toxicity of Psychotherapeutic Drugs " in the current Practitioner,' states that " Any such combination is far too dangerous for general clinical use."-I am, etc.,
Immunostimulatory RNA leads to functional reprogramming of myeloid-derived suppressor cells in pancreatic cancer
Authors: Philipp Metzger, Sabrina V. Kirchleitner, Michael Kluge, Lars M. Koenig, Christine Hörth, Carlotta A. Rambuscheck, Daniel Böhmer, Julia Ahlfeld, Sebastian Kobold, Caroline C. Friedel, Stefan Endres, Max Schnurr, Peter Duewell
Journal: Journal for ImmunoTherapy of Cancer (2019)

The tumor microenvironment (TME) combines features of regulatory cytokines and immune cell populations to evade the recognition by the immune system. Myeloid-derived suppressor cells (MDSC) comprise populations of immature myeloid cells in tumor-bearing hosts with a highly immunosuppressive capacity. We could previously identify RIG-I-like helicases (RLH) as targets for the immunotherapy of pancreatic cancer inducing immunogenic tumor cell death and type I interferons (IFN) as key mediators linking innate with adaptive immunity.Mice with orthotopically implanted KrasG12D p53fl/R172H Ptf1a-Cre (KPC) pancreatic tumors were treated intravenously with the RLH ligand polyinosinic-polycytidylic acid (poly(I:C)), and the immune cell environment in tumor and spleen was characterized. A comprehensive analysis of the suppressive capacity as well as the whole transcriptomic profile of isolated MDSC subsets was performed. Antigen presentation capability of MDSC from mice with ovalbumin (OVA)-expressing tumors was investigated in T cell proliferation assays. The role of IFN in MDSC function was investigated in Ifnar1-/- mice.MDSC were strongly induced in orthotopic KPC-derived pancreatic cancer, and frequencies of MDSC subsets correlated with tumor weight and G-CSF serum levels, whereas other immune cell populations decreased. Administration of the RLH-ligand induced a IFN-driven immune response, with increased activation of T cells and dendritic cells (DC), and a reduced suppressive capacity of both polymorphonuclear (PMN)-MDSC and monocytic (M)-MDSC fractions. Whole transcriptomic analysis confirmed an IFN-driven gene signature of MDSC, a switch from a M2/G2- towards a M1/G1-polarized phenotype, and the induction of genes involved in the antigen presentation machinery. Nevertheless, MDSC failed to present tumor antigen to T cells. Interestingly, we found MDSC with reduced suppressive function in Ifnar1-deficient hosts; however, there was a common flaw in immune cell activation, which was reflected by defective immune cell activation and tumor control.We provide evidence that the treatment with immunostimulatory RNA reprograms the TME of pancreatic cancer by reducing the suppressive activity of MDSC, polarizing myeloid cells into a M1-like state and recruiting DC. We postulate that tumor cell-targeting combination strategies may benefit from RLH-based TME remodeling. In addition, we provide novel insights into the dual role of IFN signaling in MDSC's suppressive function and provide evidence that host-intrinsic IFN signaling may be critical for MDSC to gain suppressive function during tumor development.
Impaired Nodal Shrinkage and Apoptosis Lacking Define the Adverse Independent Clinical Outcome of NOTCH1 mutated Chronic Lymphocytic Leukemia (CLL) Patients in the Age of Targeted Agents (TA)
Authors: Giovanni Del Poeta, Annalisa Biagi, Annalisa Chiarenza, Luca Laurenti, Federico Pozzo, Idanna Innocenti, Riccardo Bomben, Maria Ilaria Del Principe, Enrico Santinelli, Francesca Maria Rossi, Paolo de Fabritiis, Maria Cantonetti, Antonella Zucchetto, William Arcese, Valter Gattei
Journal: Blood (2019)
RTHP-13. EFFICACY OF FRACTIONATED GAMMA KNIFE RADIOSURGERY FOR ORBITAL CAVERNOUS HEMANGIOMA: 10-YEAR EXPERIENCE AT A SINGLE INSTITUTION
Authors: Kyung Hwan Kim, Seon-Hwan Kim, Jung-Il Lee, Doo-Sik Kong, Ho Jun Seol, Do-Hyun Nam
Journal: Neuro-Oncology (2019)

Abstract This study aimed to evaluate the efficacy and safety of fractionated gamma knife radiosurgery (GKS) for the treatment of orbital cavernous hemangioma (OCH). METHODS From January 2007 to June 2018, 34 patients who underwent fractionated GKS (median 20 Gy in 4 fractions) for OCH at a single tertiary institution were reviewed. Ophthalmic evaluations including exophthalmometry, best corrected visual acuity with the Snellen chart and Humphrey visual field were investigated. Changes in lesion volume were also analyzed. RESULTS The median age was 43 years (range, 10–67 years) and 18 patients were male (53%). The median clinical follow-up time was 42 months (range, 12–132 months). The most common presenting symptom was proptosis followed by visual impairment. Proptosis improved in all 27 patients. The mean value of proptosis was reduced from 2.9 mm to 1.1 mm (P &lt; 0.001). Of 15 patients who showed decreased visual acuity preoperatively, 12 patients (80%) had improved in vision. Preoperative visual field defects were evident in 17 patients and resolved in 15 patients (88%) after treatment. The median tumor volume at the time of GKS was 2.2 cm3 (range, 0.2–8.5 cm3). Tumor shrinkage was observed in all patients and the mean volume reduction rate was 64%. No patient experienced GKS-related ocular morbidity, though two transient GKS-related adverse events (6%) were observed. CONCLUSION Fractionated GKS is an effective and safe option for the treatment of OCH, with significant reduction in tumor volume and improvement of ophthalmic outcomes.
Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) Is a Renal Biomarker with Potential Clinical Applications in Monoclonal Gammopathy of Renal Significance (MGRS)
Authors: Eftathios Kastritis, Ioannis Papassotiriou, Maria Roussou, Maria Gavriatopoulou, Mantzou Aimilia, Erasmia Psimenou, Smaragdi Marinaki, Charikleia Gakiopoulou, Alexandra Margeli, Nikolaos Kanellias, Magdalini Migkou, Despina Fotiou, Ioannis Ntanasis-Stathopoulos, Gerasimos-Petros Papassotiriou, Aristea-Maria Papanota, Evangelos Terpos, Meletios A. Dimopoulos
Journal: Blood (2019)
Identification of FASN-Dependent Onco-Metabolic Regulation of the Pentose Phosphate Pathway (PPP) and Nucleotide Metabolism in Non-Hodgkin Lymphoma (NHL)
Authors: Ravi Dashnamoorthy, Afshin Beheshti, Xiaoyang Su, Ying Chen, Maisarah Mokhtar, Gregory Dolnikowski, Frederick Lansigan, William B Kinlaw, Sandeep Dave, Andrew M. Evens
Journal: Blood (2019)
TMIC-13. FEELING THE FORCE: DIFFERENCES IN THE MECHANOREGULATED MIGRATION OF HIGH GRADE GLIOMA BETWEEN INDIVIDUAL CELLS AND THOSE IN CONTACT WITH OTHER TUMOUR CELLS
Authors: Thuvarahan Jegathees, Victoria Prior, Geraldine O’Neill
Journal: Neuro-Oncology (2019)

Abstract A major limitation in the treatment of High Grade Gliomas (HGG) is their highly disseminating nature. While it is increasingly appreciated that the mechanical properties of the extracellular matrix, (measured as tissue elasticity, Young’s modulus, E), can independently cue cancer cell migration and invasion, to date there has been little consideration of this mechanism in HGG invasion. This is particularly important given that the brain parenchyma is a mechanically soft tissue (E values varying between 1 - 10 kPa). By measuring single cell migration we have previously demonstrated that molecular subclasses of HGGs exhibit different rigidity-sensitive and -insensitive migration. Following these findings, the present project aimed to determine whether these mechanosensitive phenotypes are maintained in the dissemination of multicellular tumour spheroids (MCTSs) that represent in vivo organisation of the primary tumour bulk. Therefore MCTSs composed of primary patient-derived HGG cells with pre-established single cell mechanosensitive phenotypes were cultured on mechanically tuneable polyacrylamide hydrogels, mimicking the range of physiological tissue rigidities. Bright-field time-lapse images were then captured over a period of 48 hours, 6 images per hour. In order to quantitate the migratory behaviours, we adapted a previously published automated image analysis program to segment the MCTS images into proliferative and migratory regions. Our analysis suggests that the cellular mechano-phenotype is affected by contact with neighbouring cells, as the migratory response to tissue stiffness is quantitatively different in the MCTSs. Our results highlight different migratory behaviour between HGG cells within the primary tumour mass versus individual cells that escape. Our results reveal the complex migratory behaviour of HGG cells and suggests that successful anti-invasive therapies will need different strategies depending on tumour cell location.
SM09419, a Novel, Small-Molecule CDC-like Kinase (CLK) Inhibitor, Demonstrates Strong Inhibition of the Wnt Signaling Pathway and Antitumor Effects in FMS-like Tyrosine Kinase 3 (FLT3)-Mutant Acute Myeloid Leukemia Models
Authors: Heekyung Chung, Emily Creger, Lauren Sitts, Kevin Chiu, Chi-Ching Mak, Sunil KC, Betty Tam, Gail Bucci, Josh Stewart, Timothy Phalen, Steven Cha
Journal: Blood (2019)
Consistency of Dosing of Turoctocog Alfa Pegol (N8-GP) throughout the Pathfinder Clinical Trials: Implications for Recommendations for Effective Prophylaxis, Bleed Resolution, and Perioperative Management
Authors: Miguel A. Escobar, Allison P. Wheeler, Steven R. Lentz, Wan Hui Ong Clausen, David Cooper
Journal: Blood (2019)
PATH-44. MULTIPLE BIOMARKER ALGORITHM BASED ON CXCL13, IL-10, IL-2 RECEPTOR, AND β2-MICROGLOBULIN IN CEREBROSPINAL FLUID TO DIAGNOSE CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Takashi Sasayama, Kazuhiro Tanaka, Masahiro Maeyama, Satoshi Nakamizo, Hirotomo Tanaka, Masamitsu Nishihara, Takanori Hirose, Yuichi Fujita, Eiji Kohmura
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Brain biopsy is the gold standard for the diagnosis of primary central nervous system lymphoma (PCNSL). However, the biopsy procedure has a risk of complications, such as hemorrhage and seizure. We have reported that cerebrospinal fluid (CSF) interleukin-10 (IL-10), soluble IL-2 receptor (sIL-2R), and β2-microglobulin (β2-MG) are the useful diagnostic biomarkers for PCNSL. Recently, the C-X-C motif chemokine ligand 13 (CXCL13) has been reported to be another useful biomarker for the PCNSL. The aim of this study was to validate the diagnostic performance of the CSF CXCL13 and diagnostic algorithm based on the combination of these biomarkers. METHODS We retrospectively examined the CSF CXCL13 concentration, as well as IL-10, sIL-2R, and β2-MG, in a case-control study (n=230). We used logistic regression analyses to create diagnostic algorithms based on these CSF biomarkers. To examine the utility of the multivariate diagnostic algorithm, we conducted the prospective study and evaluated the accuracy of this algorithm. RESULTS In case-control study, we have demonstrated that CSF CXCL13 levels were significantly higher in the patients with PCNSL (area under the curve (AUC)=0.981). A total of 84 patients were enrolled in the prospective study. The multivariate diagnostic algorithm using CSF levels of CXCL13, IL-10, sIL-2R, and β2-MG demonstrated excellent diagnostic performance: positive predictive value was 89% and negative predictive value was 100%. Four markers’ combination (CXCL13 + IL-10 + β2-MG + sIL-2R) had the highest AUC (AUC=0.998). The misdiagnosis cases of the algorithm were only 3 cases; CNS Sjögren’s syndrome, histiocytic sarcoma, and glioblastoma. In addition, CSF CXCL13 levels were prognostic biomarkers in PCNSL patients. CONCLUSIONS Our study suggests that the algorithm based on 4 CSF biomarkers had excellent diagnostic performance in CNS lymphoma. However, this algorithm should be further validated in prospective cohort studies with larger numbers of patients.
circLMTK2 acts as a sponge of miR-150-5p and promotes proliferation and metastasis in gastric cancer
Authors: Sen Wang, Dong Tang, Wei Wang, Yining Yang, Xiaoqing Wu, Liuhua Wang, Daorong Wang
Journal: Molecular Cancer (2019)

Abstract Background As a novel class of non-coding RNAs, circular RNAs (circRNAs) are key regulators of the development and progression of different cancers. However, little is known about the function and biological mechanism of circLMTK2, also named hsa_circ_0001725, in gastric cancer (GC) tumourigenesis. Methods circLMTK2 was identified in ten paired cancer specimens and adjacent normal tissues by RNA sequencing and genome-wide bioinformatic analysis and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of circLMTK2 combined with in vitro and in vivo assays were performed to prove the functional significance of circLMTK2. The molecular mechanism of circLMTK2 was demonstrated by searching the CircNet database and confirmed by RNA in vivo precipitation assays, western blotting, luciferase assays and rescue experiments. Results circLMTK2 was frequently upregulated in GC tissues, and high circLMTK2 expression was associated with poor prognosis, lymph node metastasis and poor TNM stage in GC patients. Functionally, circLMTK2 overexpression promoted GC cell proliferation and tumourigenicity in vitro and in vivo. Furthermore, ectopic circLMTK2 expression enhanced GC cell migration and invasion in vitro and tumour metastasis in vivo. In addition, we demonstrated that circLMTK2 could sponge miR-150-5p, thus indirectly regulating the c-Myc expression and contributing to GC tumourigenesis. Conclusion Our findings demonstrate that circLMTK2 functions as a tumour promoter in GC through the miR-150-5p/c-Myc axis and could thus be a prognostic predictor and therapeutic target for GC.
Second Autologous Stem Cell Transplant (ASCT) as Salvage Therapy in Patients with Relapsed Multiple Myeloma: Improved Outcomes in Patients with Longer Disease Free Interval after First ASCT.
Authors: Joseph R. Mikhael, Sahar Zadeh, Sara Samiee, Keith Stewart, Christine Chen, Suzanne Trudel, Vishal Kukreti, Norman Franke, Andrew Winter, Drew Phillips, Donna Reece
Journal: Blood (2007)
A Novel BCL-2/BCL-Xl Dual Inhibitor Overcomes Ibrutinib-Resistance Conferred By the Upregulation of Integrin Pathway and BCL-Xl
Authors: Jing Deng, Tingting Mao, Xiaojing Huang, Li Rui, Guangfeng Wang, Douglas D. Fang, Dajun Yang, Yifan Zhai
Journal: Blood (2019)
High-Throughput Functional Drug Screening and Genomic Analysis to Guide Individualized Therapy for Relapsed/Refractory Multiple Myeloma
Authors: David G. Coffey, Andrew J. Cowan, Timothy S Martins, Damian J. Green, Edward N. Libby, Rebecca W. Silbermann, Sylvia Chien, Jin Dai, Alicia Morales, Niall Curley, Bret Gary Degraaff, Ted A Gooley, Edus H. Warren, Pamela S. Becker
Journal: Blood (2019)
Validation and Improvement Opportunities of the Revised International Staging System for Multiple Myeloma: An Analysis on Mature Data from European Clinical Trials within the Harmony Big Data Platform
Authors: Mattia D'Agostino, Anders Waage, Juan-José Lahuerta, Uta Bertsch, Elena Zamagni, Lars Bullinger, Alessandra Larocca, Maria-Victoria Mateos, Niels W. C. J. Van De Donk, Hans Jürgen Salwender, Joan Bladé, Bronno van der Holt, Paola Tacchetti, Giovannino Ciccone, Sonja Zweegman, Hartmut Goldschmidt, Michele Cavo, Jesús San-Miguel, Pieter Sonneveld, Mario Boccadoro, Jesús María Hernández-Rivas
Journal: Blood (2019)
Global Fibrinolysis Analysed By Clofal Method Is Not Associated with Post-Thrombotic Syndrome or Presence of Residual Vein Thrombosis in Patients with DVT in the Chronic Phase
Authors: Beatriz Moraes Martinelli, Stephany Cares Huber, Isabella Macedo Toni, Gabriela G Yamaguti-Hayakawa, Gabriele Silva Souza Gois, Silmara Aparecida De Lima Montalvão, Joyce Maria Annichino- Bizzacchi
Journal: Blood (2019)
Origins of human milk microbiota: new evidence and arising questions
Authors: Shirin Moossavi, Meghan B. Azad
Journal: Gut Microbes (2019)

Human milk contains a diverse community of bacteria. The growing appreciation of commensal microbes and increasing availability of high-throughput technology has set the stage for a theory-driven approach to the study of milk microbiota, and translation of this knowledge to improve maternal and child health. We recently profiled the milk microbiota of healthy Canadian mothers and applied theory-driven causal modeling, finding that mode of breast milk feeding (nursing directly at the breast vs. pumping and feeding breast milk from a bottle) was significantly associated with milk microbiota composition. This observation could reflect an increased exposure to pumps and/or a decreased exposure to the infant mouth. Either way, it provides evidence for the retrograde mechanism of milk inoculation. Here, we discuss the implications of this research and related controversies, and raise new questions about the origins and function of milk bacteria.
Hierarchical Bayesian myocardial perfusion quantification
Authors: Cian M. Scannell, Amedeo Chiribiri, Adriana D.M. Villa, Marcel Breeuwer, Jack Lee
Journal: Medical Image Analysis (2019)

Purpose: Tracer-kinetic models can be used for the quantitative assessment of contrast-enhanced MRI data. However, the model-fitting can produce unreliable results due to the limited data acquired and the high noise levels. Such problems are especially prevalent in myocardial perfusion MRI leading to the compromise of constrained numerical deconvolutions and segmental signal averaging being commonly used as alternatives to the more complex tracer-kinetic models. Methods: In this work, the use of hierarchical Bayesian inference for the parameter estimation is explored. It is shown that with Bayesian inference it is possible to reliably fit the two-compartment exchange model to perfusion data. The use of prior knowledge on the ranges of kinetic parameters and the fact that neighbouring voxels are likely to have similar kinetic properties combined with a Markov chain Monte Carlo based fitting procedure significantly improves the reliability of the perfusion estimates with compared to the traditional least-squares approach. The method is assessed using both simulated and patient data. Results: The average (standard deviation) normalised mean square error for the distinct noise realisations of a simulation phantom falls from 0.32 (0.55) with the least-squares fitting to 0.13 (0.2) using Bayesian inference. The assessment of the presence of coronary artery disease based purely on the quantitative MBF maps obtained using Bayesian inference matches the visual assessment in all 24 slices. When using the maps obtained by the least-squares fitting, a corresponding assessment is only achieved in 16/24 slices. Conclusion: Bayesian inference allows a reliable, fully automated and user-independent assessment of myocardial perfusion on a voxel-wise level using the two-compartment exchange model.