tbuckley/cabot-search huggingface dataset:
Venetoclax in Combination with High-Dose Chemotherapy Is Active and Well-Tolerated in Children with Relapsed or Refractory Acute Myeloid Leukemia
Authors: Seth E Karol, Thomas Alexander, Amit Budraja, Stanley Pounds, Kristin E Canavera, Lei Wang, Joshua Wolf, Jeffery M. Klco, Ahmed Hamed Salem, Tammy Palenski, Norman J. Lacayo, Ching-Hon Pui, Joseph T. Opferman, Jeffrey Rubnitz
Journal: Blood (2019)
Outcomes for Patients with Primary or Secondary Central System Lymphoma Treated with Ibrutinib: A Multicentre Retrospective Analysis
Authors: Katharine L Lewis, Kate Manos, John Casey, Julie Crawford, Shir-Jing Ho, Samar Issa, Andrew Grigg, Peter Wood, Maher K. Gandhi, Eliza A Hawkes, Chan Y. Cheah
Journal: Blood (2019)
ATIM-30. COMBATING RECURRENT GLIOBLASTOMA WITH MDNA55, AN INTERLEUKIN-4 RECEPTOR TARGETED IMMUNOTHERAPY, THROUGH MRI-GUIDED CONVECTIVE DELIVERY
Authors: John Sampson, Achal Singh Achrol, Manish Aghi, Krystof Bankiewicz, Steven Brem, Andrew Brenner, Nicholas Butowski, Chandtip Chandhasin, Sajeel Chowdhary, Melissa Coello, John R Floyd, Santosh Kesari, Fahar Merchant, Nina Merchant, Dina Randazzo, Michael Vogelbaum, Frank Vrionis, Miroslaw Zabek, Martin Bexon
Journal: Neuro-Oncology (2019)

Abstract MDNA55, an IL4R-directed toxin, is being studied in a Phase 2b trial in recurrent GBM (rGBM) patients at first or second relapse. MDNA55 is co-infused with Gadolinium-based contrast agent and delivered as a single intratumoral infusion using Convection Enhanced Delivery (CED). Primary endpoint is median Overall Survival (mOS) and secondary endpoint is objective response rate (ORR) assessed by mRANO-based criteria incorporating advanced imaging modalities. Enrollment is complete (n=46). Current safety data show similar profile to previous MDNA55 trials with no systemic toxicities or drug related deaths. Current mOS in subjects treated with low doses of MDNA55 (median 63µg; n=21) is 11.8 months. When stratified by IL4R expression, a biomarker for more aggressive GBM, IL4R+ve subjects (mOS 15.2 months; n=8) show a survival advantage of 7 months compared to IL4R-ve subjects (mOS 8.1 months; n=10). Updated survival and response outcomes including subjects receiving the high dose (median 180µg; n=25) and stratification by IL4R expression will be reported. Review of serial imaging within 90 days following MDNA55 treatment demonstrated tumor shrinkage or stabilization from baseline in 19/42 evaluable subjects (disease control rate of 45%). To account for initial pseudo-progression in some subjects, tumor response was also assessed from nadir: 83% (35/42) showed disease control. Multi-parametric MRI biomarkers including relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) measurements demonstrated distinct imaging phenotypes among different disease states (pseudo-progression vs true-progression, pseudo-response vs true-response) and improved response staging. This trial is advancing neurosurgical methods for CED, potential of IL4R expression as a biomarker to select GBM patients most likely to benefit from MDNA55 treatment, and optimal use of multi-parametric MRI as an adjunct to clinical decision making. The improved survival and disease control seen after only a single infusion of MDNA55, especially in IL4R+ve subjects, may provide promising clinical benefit for rGBM patients.
PP2A Activators Enhance Efficacy of FLT3 Inhibitors in FLT3-ITD Acute Myeloid Leukemia Cells through AKT Inactivation-Dependent Pim-1 and c-Myc Proteasomal Degradation
Authors: Mario Scarpa, Prerna Singh, Shivani Kapoor, Jonelle K. Lee, Sandrine Niyongere, Goutham Narla, Danilo Perrotti, Maria R. Baer
Journal: Blood (2019)
Testosterone replacement in young male cancer survivors: A 6-month double-blind randomised placebo-controlled trial
Authors: Jennifer S. Walsh, Helen Marshall, Isabelle L. Smith, Diana M. Greenfield, Jayne Swain, Emma Best, James Ashton, Julia M. Brown, Robert Huddart, Robert E. Coleman, John A. Snowden, Richard J. Ross
Journal: PLoS Medicine (2019)

Background Young male cancer survivors have lower testosterone levels, higher fat mass, and worse quality of life (QoL) than age-matched healthy controls. Low testosterone in cancer survivors can be due to orchidectomy or effects of chemotherapy and radiotherapy. We have undertaken a double-blind, placebo-controlled, 6-month trial of testosterone replacement in young male cancer survivors with borderline low testosterone (7–12 nmol/l). Methods and findings This was a multicentre United Kingdom study conducted in secondary care hospital outpatients. Male survivors of testicular cancer, lymphoma, and leukaemia aged 25–50 years with morning total serum testosterone 7–12 nmol/l were recruited. A total of 136 men were randomised between July 2012 and February 2015 (42.6% aged 25–37 years, 57.4% 38–50 years, 88% testicular cancer, 10% lymphoma, matched for body mass index [BMI]). Participants were randomised 1:1 to receive testosterone (Tostran 2% gel) or placebo for 26 weeks. A dose titration was performed after 2 weeks. The coprimary end points were trunk fat mass and SF36 Physical Functioning score (SF36-PF) at 26 weeks by intention to treat. At 26 weeks, testosterone treatment compared with placebo was associated with decreased trunk fat mass (−0.9 kg, 95% CI −1.6 to −0.3, p = 0.0073), decreased whole-body fat mass (−1.8 kg, 95% CI −2.9 to −0.7, p = 0.0016), and increased lean body mass (1.5 kg, 95% CI 0.9–2.1, p < 0.001). Decrease in fat mass was greatest in those with a high truncal fat mass at baseline. There was no treatment effect on SF36-PF or any other QoL scores. Testosterone treatment was well tolerated. The limitations of our study were as follows: a relatively short duration of treatment, only three cancer groups included, and no hard end point data such as cardiovascular events. Conclusions In young male cancer survivors with low-normal morning total serum testosterone, replacement with testosterone is associated with an improvement in body composition. Trial registration ISRCTN: 70274195, EudraCT: 2011-000677-31.
Comparison of Myeloablative (CyTBI, BuCy) Versus Reduced-Intensity (FluBu2TBI400) Peripheral Blood Stem Cell Transplantation in Acute Myeloid Leukemia Patients with Low WT1 Expression Level at Transplant
Authors: Silvia Park, GI June MIN, Sung-Soo Park, Seung-Ah Yahng, Young-Woo Jeon, Seung-Hwan Shin, Jae-Ho Yoon, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Hee-Je Kim
Journal: Blood (2019)
Association Between Switching to a High-Deductible Health Plan and Discontinuation of Type 2 Diabetes Treatment
Authors: A. Mark Fendrick, Jason D. Buxbaum, Yuexin Tang, Anna Vlahiotis, Donna McMorrow, Swapnil Rajpathak, Michael E. Chernew
Journal: JAMA Network Open (2019)

High-deductible health plans (HDHPs) are a common cost-savings option for employers but may lead to underuse of necessary treatments because beneficiaries bear the full cost of health care, including medications, until a deductible is met.To evaluate the association between switching from a non-HDHP to an HDHP and discontinuation of antihyperglycemic medication and to assess whether the association differs in patients using branded vs generic antihyperglycemic medications.This retrospective matched cohort study used administrative claims from MarketScan databases to identify commercially insured adult patients with type 2 diabetes who used at least 1 antihyperglycemic medication in 2013. Patients in the HDHP cohort (n = 1490) were matched by propensity scores to a non-HDPH control cohort (n = 1490). Data were collected and analyzed from January 1, 2013, through December 31, 2014.Switching from a non-HDHP in 2013 to a full replacement HDHP in 2014 (no non-HDHP option offered) vs staying on a non-HDHP.Difference-in-differences models estimated discontinuation of branded and generic antihyperglycemic medications.Among the 2980 patients included in the analysis (1932 men [64.8%]; mean [SD] age, HDHP cohort: 52.6 [6.9] years; non-HDHP cohort: 52.7 [7.3] years), no difference between the HDHP and non-HDHP cohorts was found in unadjusted follow-up discontinuation rates for all antihyperglycemic medications (255 [22.7%] vs 255 [23.3%]; P = .72); however, among patients using branded medication, a significantly greater proportion of patients in the HDHP group did not refill branded medications (81 of 396 [20.5%] vs 61 of 437 [14.0%]; P = .009). Difference-in-differences models were not statistically significant.These findings suggest switching to an HDHP is associated with discontinuation specifically of branded medications. Unintended health consequences may result and should be considered by employers making health care benefit decisions.
Shared Genomic Alterations in Patients with Co-Existing Myeloproliferative Neoplasms and Angioimmunoblastic T-Cell Lymphoma
Authors: Johanne Marie Holst, Martin Bjerregaard Pedersen, Marcus C Hansen, Trine Lindhardt Plesner, Henrik Frederiksen, Michael Møller, Stephen Hamilton-Dutoit, Peter Noergaard, Bo Kok Mortensen, Danilo Fiore, Chao Wang, Weiwei Zhang, Wayne Tam, Maja Ludvigsen, Wing C. Chan, Giorgio Inghirami, Francesco d'Amore
Journal: Blood (2019)
Haplo-Cord Transplantation with Anti-Thymocyte Globulin: Comparative Clinical Outcomes with or without Routine G-CSF Administration
Authors: Nina Orfali, Alexandra Gomez-Arteaga, Danielle Guarneri, Jingmei Hsu, Adrienne A. Phillips, Usama Gergis, Tsiporah B. Shore, Sebastian A. Mayer, Koen Van Besien
Journal: Blood (2019)
Changing the Fate of Children with Acute Lymphoblastic Leukemia (ALL) in a Limited Resources Setting
Authors: Yajaira Valentine Jimenez-Antolinez, Julia Esther Colunga Pedraza, José Eduardo Mares-Gil, Emma Lizeth Estrada, Jesus Mauricio Gonzalez-Diaz, David Gomez-Almaguer, Oscar Gonzalez Llano
Journal: Blood (2019)
Flotetuzumab, an Investigational CD123 x CD3 Bispecific Dart® Protein, in Salvage Therapy for Primary Refractory and Early Relapsed Acute Myeloid Leukemia (AML) Patients
Authors: Geoffrey L. Uy, Ibrahim Aldoss, Matthew C Foster, David A Sallman, Kendra L. Sweet, David A. Rizzieri, Peter H. Sayre, Anjali S. Advani, Ashkan Emadi, Matthew J. Wieduwilt, Norbert Vey, Fabio Ciceri, Matteo Giovanni Carrabba, Tamara Moyo, Sarah E. Church, Michael P. Rettig, Martha L. Arellano, John E. Godwin, Bob Löwenberg, Gerwin Huls, Farhad Ravandi, John Muth, Kathy Tran, Mojca Jongen-Lavrencic, Erin Timmeny, Max S. Topp, Stefania Paolini, Kuo Guo, Teia Curtis, Jian Zhao, Jayakumar Vadakekolathu, Jon M. Wigginton, Ezio Bonvini, Sergio Rutella, Roland B. Walter, Jan K Davidson-Moncada, John F. DiPersio
Journal: Blood (2019)
Treatment of Acute Mastitis
Authors: J. Macleod
Journal: BMJ (1947)

JOURNAL86quently observed after cortical mastoidectomy performed by the post-aural route has not been found following this endaural tech- nique.The lesion in the cases in question was acute or subacute mastoiditis; the ear drums and wounds were healed within a week of operation.Convalescence appeared to be aided by pre-and post- operative systemic penicillin treatment.-Iam, etc., Warwick.
Identification of Medical Documents
Authors: L. Hogben, M. M. Johnstone, K. W. Cross
Journal: BMJ (1948)

To fulfil admInistrative requirements for cross-reference with respect to successive admissions of one and the same person to the same medical institution and to different ones, or to subserve the ends of research involving reference to original records, a system of medical documentation must make provision for identification of individual patients.Ipso facto the method of designation must be highly specific in the sense that it excludes the possibility of confusing two individuals.It must also be suitable for transcription by recourse to a numerical code.Otherwise it is not feasible to take advantage of current mechanical methods of sorting and tabulation involving the use of punch-cards.For the purposes of the punch-card, numerical coding of the birth name is unsatisfactory both because it monopolizes a considerable fraction of space available for other uses and because allocation of requisite columns is highly variable.The complete birth name.ofan individual may require any number of letters, from a minimum of about seven-e.g., May Hall-to a maximum of about 30.For instance, Henry William Howard Waterhouse would entail the allocation of 28 columns by the alpha system of punching and sorting with respect to a single letter of the alphabet per column. Frequency of SurnamesEqually important, though too rarely recognized, is the fact that birth names are not highly specific.Farr recognized this long ago, and emphasized its statistical implications in words which are still worthy of citation:" From the indexes of the registers for the year 1853, the probable number of persons in England and Wales bearing each of the 50 most frequent surnames has been computed. ..The persons by whom these 50 surnames are borne amount to about 3,253,800; nearly one-sixth of the entire population of England and Wales.On an average, it seems, one person in 73 is a Smith, one in 76 a Jones, one in 115 a Williams, one in 148 a Taylor, one in 162 a Davies, and one in 174 a Brown."In an investigation into the frequency of surnames in aMidland telephone directory we found that the following seven names accounted for 5.6% of 88,351 persons listed: Smith, 1,330 (1.5%);Jones, 965 (1.1%); Williams, 614 (0.70%); Taylor, 550 (0.62%); Green, 520 (0.59%);Brown, 502 (0.57%); Evans, 468 (0.53%).
NUDT15 Genetic Variation Is the Strongest Predictive Marker of Tolerance to 6-Mercaptopurine in Japanese Childhood ALL Patients: A Genome-Wide Association Study
Authors: Yoichi Tanaka, Kevin Y Urayama, Makiko Mori, Daisuke Hasegawa, Yasushi Noguchi, Masakatsu Yanagimachi, Dai Keino, Setsuo Ota, Koshi Akahane, Mayumi Hangai, Takahisa Kawaguchi, Masatoshi Takagi, Katsuyoshi Koh, Fumihiko Matsuda, Atsushi Manabe
Journal: Blood (2019)
CTCF modulates allele-specific sub-TAD organization and imprinted gene activity at the mouse Dlk1-Dio3 and Igf2-H19 domains
Authors: David Llères, Benoît Moindrot, Rakesh Pathak, Vincent Piras, Mélody Matelot, Benoît Pignard, Alice Marchand, Mallory Poncelet, Aurélien Perrin, Virgile Tellier, Robert Feil, Daan Noordermeer
Journal: Genome biology (2019)

Genomic imprinting is essential for mammalian development and provides a unique paradigm to explore intra-cellular differences in chromatin configuration. So far, the detailed allele-specific chromatin organization of imprinted gene domains has mostly been lacking. Here, we explored the chromatin structure of the two conserved imprinted domains controlled by paternal DNA methylation imprints-the Igf2-H19 and Dlk1-Dio3 domains-and assessed the involvement of the insulator protein CTCF in mouse cells.Both imprinted domains are located within overarching topologically associating domains (TADs) that are similar on both parental chromosomes. At each domain, a single differentially methylated region is bound by CTCF on the maternal chromosome only, in addition to multiple instances of bi-allelic CTCF binding. Combinations of allelic 4C-seq and DNA-FISH revealed that bi-allelic CTCF binding alone, on the paternal chromosome, correlates with a first level of sub-TAD structure. On the maternal chromosome, additional CTCF binding at the differentially methylated region adds a further layer of sub-TAD organization, which essentially hijacks the existing paternal-specific sub-TAD organization. Perturbation of maternal-specific CTCF binding site at the Dlk1-Dio3 locus, using genome editing, results in perturbed sub-TAD organization and bi-allelic Dlk1 activation during differentiation.Maternal allele-specific CTCF binding at the imprinted Igf2-H19 and the Dlk1-Dio3 domains adds an additional layer of sub-TAD organization, on top of an existing three-dimensional configuration and prior to imprinted activation of protein-coding genes. We speculate that this allele-specific sub-TAD organization provides an instructive or permissive context for imprinted gene activation during development.
Developmental Systems Drift and the Drivers of Sex Chromosome Evolution
Authors: Caroline M S Cauret, Marie-Theres Gansauge, Andrew S Tupper, Benjamin L S Furman, Martin Knytl, Xue-Ying Song, Eli Greenbaum, Matthias Meyer, Ben J Evans
Journal: Molecular Biology and Evolution (2019)

Abstract Phenotypic invariance—the outcome of purifying selection—is a hallmark of biological importance. However, invariant phenotypes might be controlled by diverged genetic systems in different species. Here, we explore how an important and invariant phenotype—the development of sexually differentiated individuals—is controlled in over two dozen species in the frog family Pipidae. We uncovered evidence in different species for 1) an ancestral W chromosome that is not found in many females and is found in some males, 2) independent losses and 3) autosomal segregation of this W chromosome, 4) changes in male versus female heterogamy, and 5) substantial variation among species in recombination suppression on sex chromosomes. We further provide evidence of, and evolutionary context for, the origins of at least seven distinct systems for regulating sex determination among three closely related genera. These systems are distinct in their genomic locations, evolutionary origins, and/or male versus female heterogamy. Our findings demonstrate that the developmental control of sexual differentiation changed via loss, sidelining, and empowerment of a mechanistically influential gene, and offer insights into novel factors that impinge on the diverse evolutionary fates of sex chromosomes.
Radiation-Free Protocol for Patients with Acute Lymphoblastic Leukemia and Mixed Phenotype Acute Leukemia Undergoing Induction Chemotherapy and Allogeneic Hematopoietic Cell Transplantation - a Multicenter Historical Prospective Study
Authors: Odelia Amit, Yael Bar-On, Irit Avivi, Tsila Zuckerman, Galit Perets, Israel Henig, Itai Levi, Dana Yehudai-Ofir, Shimrit Ringelstein Harlev, Ron Ram
Journal: Blood (2019)
Epigenetic Modulation of CD48 By NPM-ALK Promotes Immune Evasion in ALK+ ALCL
Authors: Rui Wu, Elena Ivan, Anagh Anant Sahasrabuddhe, Timothy Shaw, Charles G. Mullighan, Vasiliki Leventaki, Kojo S. J. Elenitoba-Johnson, Megan S. Lim
Journal: Blood (2019)
Tissue-Resident PSGL1loCD4+ T Cells Interact with B Cells Via PD-1 and PD-L2 in Gvhd Target Tissues to Augment Autoimmune-like Chronic Gvhd
Authors: Xiaohui Kong, Deye Zeng, Xiwei Wu, Shijie Yang, Bixin Wang, Qingxiao Song, Yongping Zhu, Martha Salas, Hanjun Qin, Ubaydah Nasri, Ryotaro Nakamura, Paul J Martin, Aimin Huang, Defu Zeng
Journal: Blood (2019)
Nascent Transcript and Single Cell Rnaseq Analysis Defines the Mechanism of Action of the LSD1 Inhibitor INCB059872 in Myeloid Leukemia
Authors: Gretchen Johnston, Haley E. Ramsey, Kristy Stengel, Shilpa Sampathi, Pankaj Acharya, Maria Arrate, Matthew C. Stubbs, Timothy Burn, Scott Hiebert, Michael R. Savona
Journal: Blood (2019)
CBMT-12. FOCAD LOSS IMPACTS MICROTUBULE ASSEMBLY, G2/M PROGRESSION AND PATIENT SURVIVAL IN ASTROCYTIC GLIOMAS
Authors: Frank Brand, Alisa Förster, Anne Kosfeld, Martin Bucher, Carina Thomé, Marc Raab, Manfred Westphal, Torsten Pietsch, Andreas von Deimling, Guido Reifenberger, Peter Claus, Bettina Hentschel, Michael Weller, Ruthild Weber
Journal: Neuro-Oncology (2019)

Abstract In search of novel genes associated with glioma pathogenesis, we have previously shown that KIAA1797/FOCAD is frequently deleted in malignant gliomas and that the encoded focadhesin functions as a tumor suppressor impacting proliferation and migration of glioma cells in vitro and in vivo. Here, we examine an association of FOCAD copy number loss with overall survival of patients with astrocytic gliomas, and address the molecular mechanisms that govern the suppressive effect of focadhesin on glioma growth. FOCAD loss was associated with inferior outcome in patients with isocitrate dehydrogenase 1 or 2 (IDH)-mutant astrocytic gliomas of WHO grades II-IV. Multivariate analysis considering age at diagnosis, IDH mutation and MGMT promoter methylation status confirmed FOCAD loss as a prognostic factor for overall survival. Using a yeast two-hybrid screen and pull-down assays, we identified tubulin beta-6 and other tubulin family members as novel focadhesin-interacting partners. We demonstrate that tubulins and focadhesin co-localize at the centrosome and that focadhesin is enriched in proximity to centrioles. Focadhesin is recruited to microtubules via its interaction partner SLAIN motif family member 2 and reduces microtubule assembly rates, possibly explaining why focadhesin decreases cell migration. During the cell cycle, focadhesin levels peak in G2/M phase and influence time-dependent G2/M progression possibly via polo like kinase 1 phosphorylation, providing an explanation for focadhesin-dependent cell growth reduction. We conclude that FOCAD loss may promote biological aggressiveness and worsen clinical outcome of diffuse astrocytic gliomas by enhancing microtubule assembly and accelerating G2/M phase progression.
Genome-Wide RNAi Screen Identifies The Mechanistic Role For DOT1L In MLL-Rearranged Leukemia
Authors: Chun-Wei David Chen, Amit U. Sinha, Jun Qi, Aniruddha J Deshpande, Nan Zhu, Richard Koche, Rowena Eng, Jenny Chang, William C. Hahn, James E Bradner, Scott A. Armstrong
Journal: Blood (2013)
Canadian pharmacist receives award for standing up to campaigners over unproven cancer treatment
Authors: Jane Feinmann
Journal: BMJ (2019)

A Canadian community pharmacist has been recognised by the UK charity Sense About Science for enduring a “barrage of harassment” from alternative practitioners when he persisted in speaking out against their lobbying of the Quebec government to gain “approval and reimbursement” for an unproven therapy—high dose vitamin C injections—as an alternative treatment for cancer.

Olivier Bernard, from Quebec, Canada, was awarded the prestigious John Maddox prize for “standing up for science” at a ceremony in London …
Prescription opioid use and misuse among adolescents and young adults in the United States: A national survey study
Authors: Joel D. Hudgins, John J. Porter, Michael C. Monuteaux, Florence T. Bourgeois
Journal: PLoS Medicine (2019)

Prescription opioid misuse has become a leading cause of unintentional injury and death among adolescents and young adults in the United States. However, there is limited information on how adolescents and young adults obtain prescription opioids. There are also inadequate recent data on the prevalence of additional drug abuse among those misusing prescription opioids. In this study, we evaluated past-year prevalence of prescription opioid use and misuse, sources of prescription opioids, and additional substance use among adolescents and young adults.