tbuckley/cabot-search huggingface dataset:
Pulmonary Alveolar Microlithiasis
Authors: R. Viswanathan
Journal: Thorax (1962)

The object of this communication is to review the literature on pulmonary alveolar microlithiasis, to give a description of the disease on the basis of the information available, and to report on two new cases seen in siblings.As far as I am aware, no previous report of any case has been made from India. REVIEW OF THE LITERATUREPulmonary alveolar microlithiasis is the name given by Puhr (1933) to a condition characterized by multiple minute calcifications mostly affecting the alveoli, giving a typical radiographic picture, and having a tendency to appear in siblings.A comprehensive review of the disease has been given by Sosman, Dodd, Jones, and Pillmore (1957) with reports of 24 cases seen by them.They reviewed 22 previous case reports (Table I).
Maintenance of Health-Related Quality of Life in the Phase 4 BYOND Study of Bosutinib for Pretreated Chronic Phase Chronic Myeloid Leukemia
Authors: Tim H Brümmendorf, Carlo Gambacorti-Passerini, Camille Abboud, Justin M. Watts, Gianantonio Rosti, Alexander Russell-Smith, Andrea Viqueira, Arlene Reisman, Frank Giles, Andreas Hochhaus
Journal: Blood (2019)
Β-Catenin and Axl Receptor Tyrosine Kinase Modulation in CLL B-Cells with Co-Culture on Marrow Stromal Cells: Implications for Drug Resistance
Authors: Sutapa Sinha, Charla R Secreto, Justin C. Boysen, Steven L. Warner, David J. Bearss, Asish K Ghosh, Neil E. Kay
Journal: Blood (2019)
Normal Hemoglobin Concentrations in Obstructive Sleep Apnea and Associated Neocytolysis-Mediated Hemolysis and Inflammation Mediated Suppression of Expected Elevated Hemoglobin
Authors: Jihyun Song, Krishna M Sundar, Monika Horvathova, Tsewang Tashi, Carsten Lundby, Tomas Ganz, Josef T. Prchal
Journal: Blood (2019)
Final Development of the First Generic Quality of Life and Symptoms Measure Specific for Hematological Malignancies: The HM-PRO
Authors: Pushpendra Goswami, Tatiana Ionova, Esther Natalie Oliva, Roger Else, Jonathan Kell, Adele K. Fielding, Daniel Jennings, Marina Karakantza, Saad Al-Ismail, Graham P. Collins, Stewart McConnell, Catherine Langton, Sam Salek
Journal: Blood (2019)
Modeling the Behavior of Hematopoietic Compartments from Stem to Red Cells in Murine Steady State and Stress Hematopoiesis
Authors: Celine Bonnet, Panhong Gou, Vincent Bensaye, Catherine Lacout, Karine Bailly, Marie-helene Schlagetter, Evelyne Lauret, Sylvie Meleard, Stephane Giraudier
Journal: Blood (2019)
TMIC-46. GLIOMA-INDUCED SYNAPTOGENESIS IS ENRICHED WITHIN FUNCTIONAL CONNECTIVITY NETWORK HUBS AND INFLUENCES LANGUAGE PROCESSING IN ADULT IDH WT GLIOBLASTOMA
Authors: Saritha Krishna, Sofia Kakaizada, Claudia Valdivia, Kyounghee Seo, David Raleigh, Anne Findlay, Nyle Almeida, Rasika Sudharshan, Abrar Choudhury, David Brang, Srikantan Nagarajan, Mitchel Berger, Michelle Monje, Shawn Hervey-Jumper
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Little is known about the mechanisms by which gliomas integrate into functional neural networks and influence complex cognitive processes such as language. Glioma-neuron interactions are bidirectional, with increased neuronal activity promoting tumor growth and the latter in turn influencing neuronal excitability and synaptic connections. It remains unknown whether glioma-neuron interactions play a role in maintaining long-range neural networks subserving cognition in humans. We test the hypothesis that glioma-neuron interactions (“synaptogenic glioma cells”) are enriched within intratumoral high functional connectivity (FC) network hubs, thereby influencing language processing via release of synaptogenic factors into the tumor microenvironment. METHODS We employed magnetoencephalography imaginary coherence measures to identify intratumoral high (HFC) and low (LFC) functional connectivity network hubs in newly diagnosed glioblastoma patients. Primary patient samples and cultures from HFC and LFC sites were assessed for pre and post-synaptic marker expression (IF), cocultured with murine hippocampal neurons, and induced neuron organoids. ECOG Field recordings were performed on HFC/LFC tumors. Secreted proteins were measured from patient serum and LFC/HFC culture supernatant. Language assessments were performed to correlate task performance with FC measures. RESULTS Primary patient samples from HFC regions are enriched for glioblastoma cells with a synaptogenic profile as characterized by pre- and post-synaptic marker expression at both tissue and cellular level (coculture with mouse hippocampal neuron and organoid models). RNA sequencing and proteomic analyses from HFC samples revealed a neurogenic signature including thrombospondin 1 (TSP1). Overexpression of TSP1 in LFC primary patient cultures rescues the synaptogenic and proliferative phenotype. Importantly, we found a linear relationship between intratumoral HFC with patient serum TSP1 (ELISA) with a further correlation with language task performance. CONCLUSION An enriched population of synaptogenic glioma cells are organized within intratumoral high network connectivity regions. Glioma-induced neuronal synaptogenesis contributes to the microenvironment in support of network connectivity through secretion of TSP1.
SURG-30. CLINICAL COURSE OF IDH-MUTATED LOW-GRADE GLIOMAS DURING THE POSTSURGICAL ACTIVE MONITORING PHASE: ASYMPTOMATIC PATIENTS, WELL CONTROLLED SEIZURES, BUT CONTINUOUS GROWTH OF TUMOR RESIDUES
Authors: Maarten Wijnenga, Matin Daftari Besheli, Pim French, Hendrikus Dubbink, Marion Smits, Johan Kros, Jacoline E C Bromberg, Walter Taal, Clemens Dirven, Arnaud Vincent, Martin van den Bent
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Postponing adjuvant treatment after resection in IDH-mutated low-grade glioma (LGG) seems appropriate in selected patients. Here we describe the clinical course of these patients during post-resection active monitoring with MRI scans, as literature on this topic is scarce. METHODS We included IDH-mutated LGG patients that underwent surgery between 2003–2016, with clinical follow-up including MR scans available. Samples were classified according to the 2016 WHO classification. We collected baseline clinical information, estimates of seizure control during follow-up, longitudinal evolution of post-resection LGG volumes when adjuvant therapy was postponed, and the clinicians’ reasons to either start immediate adjuvant treatment or postpone treatment, and reasons to initiate adjuvant treatment in later stage. We compared patients that underwent immediate postsurgical adjuvant treatment with patients that underwent active MRI monitoring until further progression. RESULTS AND CONCLUSIONS 197 patients were included, of which 108 were IDH-mutated astrocytomas, and 89 were oligodendrogliomas. Of these, 97 patients were actively followed with MRI scans, and 100 patients underwent immediate adjuvant therapy after initial surgery. Patients that received immediate adjuvant therapy were older and had less extensive resections than patients wherein adjuvant treatment was postponed (median age 45 years vs. 37 years, P&lt; 0.001; median postoperative tumor volume 31cm3 vs 2.68cm3, P&lt; 0.001). The duration of the active surveillance period in the patients wherein adjuvant treatment was postponed correlated with the extent of resection, with shorter time until adjuvant treatment in case of larger postoperative tumor volumes. All LGG lesions showed continuous growth during the active surveillance period, with median growth rates of 3mm/year for oligodendrogliomas and 4mm/year in IDH- mutated astrocytomas (P = 0.0093). Seizures were well controlled, with the majority of patients using only one anti-epileptic drug. The majority of patients stayed asymptomatic during follow-up, and the reason to initiate further adjuvant treatment was always radiological growth.
Oral Contraceptives and Coronary Thrombosis
Authors: G. Lloyd
Journal: BMJ (1965)

latrogenic Ulcers of the Small Intestine SIR,--We should like to report another possible case of ileal ulceration and perforation in a patient receiving enteric-coated potassium-chloride tablets but not chlorothiazide.In June, 1964, a woman aged 58 was diagnosed as having pemphigus vulgaris.This proved difficult to control and necessitated an initial suppressive dose of 210 mg.prednisolone and 120 units corticotrophin gel daily.Control was achieved and the steroids were gradually withdrawn during the following four months without recurrence of the pemphigus.Her serum potassium fell steadily during treatment despite constant administration of enteric-coated potassium-chloride tablets 1 g.twice daily in- creasing on 19 August to 2 g. -three times a day.It was suspected, and later confirmed, that she was not taking all her potassium and she dis- charged herself on 26 August with a serum potassium of only 2.7 mEq/l.She was warned of the possible consequences and by 2 Septem- ber her potassium was 5.1 rising to 5.5 mEq/l., suggesting that she was now taking the full dose of potassium chloride-that is 6 g. daily.At about this time she began to complain of vague lower abdominal pain associated with tenderness and diarrhoea.Her E.S.R., which tad varied from 25 to 45 mm. (Westergren), rose to 85 mm./hr.and has since fluctuated between 44 and 116 mm.On 1 November the pulse rate rose suddenly to 120 and she was mildly shocked.A gastrointestinal perforation was sus- pected and she consented to admission but re- fused operation.The haemoglobin fell to 58% and occult bloods were positive.Triamcino- lone was finally discontinued on 22 November but potassium chloride was continued.She gradually improved until on 10 December 1964, a barium enema revealed a fistula between the ileum and pelvic colon.A few diverticula were present in the colon.At no time during her illness were thiazide-type diuretics administered.
PDTM-39. CRACKING THE HISTONE CODE: REVEALING THERAPEUTIC EPIGENETIC TARGETS THROUGH HISTONE H3 TAIL ANALYSIS OF DIFFUSE INTRINSIC PONTINE GLIOMA
Authors: Daphne Li, Tina Huang, Jeannie Camarillo, Jin Qi, Hannah Weiss, Javad Nazarian, Paul Thomas, Amanda Saratsis
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Diffuse intrinsic pontine glioma (DIPG) is a highly morbid pediatric cancer. Up to 80% harbor a Histone H3K27M mutation, which alters wild type Histone H3 protein post-translational modifications (PTMs) and genomic enrichment patterns to impact chromatin structure and transcription regulation. We previously identified tumorigenic patterns of H3K27Ac/bromodomain co-enrichment in DIPG, and demonstrated pre-clinical efficacy of bromodomain inhibition (JQ1). Here, we employ a novel proteomics platform, developed at our institution, to further elucidate the impact of H3K7M mutation on glioma histone codes and response to bromodomain inhibition. METHODS Epiproteomic analysis was performed on pediatric glioma cell lines (H3K27 WT n=2, H3K27M n=2) to characterize 95 distinct Histone H3.3 and H3.1 N-terminal tail modification states. Cells were treated with JQ1 or DMSO, and collected at 0h, 24h, 48h. Histones were extracted from isolated nuclei, immunopurified, and analyzed by LC-MS/MS. Results were integrated with RNA-Seq and ChIP Seq results (H3K27M, H3K27Ac, H3K27me3, H3K4me1, H3K4me3) from the same DIPG cell lines. Pediatric glioma tissues (H3K27M WT n=3, H3K27M n= 9) were similarly analyzed to validate cell line results. RESULTS Cell PTM profiles cluster by H3 mutation status on unsupervised analysis. Relative H3 PTM abundance were compared across cell lines by tumor location, H3 mutation status, and in response to treatment. Significant differential genomic enrichment H3K27M and H3.3 WT proteins, H3K27Me3 and H3K27Ac were observed between mutant and wild type cell lines with epigenetic-targeted therapy, correlating with cell transcriptomes. CONCLUSIONS Histone H3 tail epiproteomic analysis reveals DIPG histone codes in situ, revealing the effects of bromodomain inhibition on the tumor epigenetic landscape and providing new insight to the mechanism of tumor formation and therapy response. Further investigation of the utility of these signatures as biomarkers for diagnosis and longitudinal monitoring of treatment response are therefore currently underway.
GPS mobility as a digital biomarker of negative symptoms in schizophrenia: a case control study
Authors: Colin A. Depp, Jesse Bashem, Raeanne C. Moore, Jason L. Holden, Tanya Mikhael, Joel Swendsen, Philip D. Harvey, Eric L. Granholm
Journal: npj Digital Medicine (2019)

Abstract Mobility is an important correlate of physical, cognitive, and mental health in chronic illness, and can be measured passively with mobile phone global positional satellite (GPS) sensors. To date, GPS data have been reported in a few studies of schizophrenia, yet it is unclear whether these data correlate with concurrent momentary reports of location, vary by people with schizophrenia and healthy comparison subjects, or associate with symptom clusters in schizophrenia. A total of 142 participants with schizophrenia ( n = 86) or healthy comparison subjects ( n = 56) completed 7 days of ecological momentary assessment (EMA) reports of location and behavior, and simultaneous GPS locations were tracked every five minutes. We found that GPS-derived indicators of average distance travelled overall and distance from home, as well as percent of GPS samples at home were highly correlated with EMA reports of location at the day- and week-averaged level. GPS-based mobility indicators were lower in schizophrenia with medium to large effect sizes. Less GPS mobility was related to greater negative symptom severity, particularly diminished motivation, whereas greater GPS mobility was weakly associated with more community functioning. Neurocognition, depression, and positive symptoms were not associated with mobility indicators. Therefore, passive GPS sensing could provide a low-burden proxy measure of important outcomes in schizophrenia, including negative symptoms and possibly of functioning. As such, passive GPS sensing could be used for monitoring and timely interventions for negative symptoms in young persons at high risk for schizophrenia.
A Multi-Omic Precision Medicine Clinical Trial in Acute Leukemia
Authors: Pamela S. Becker, Vivian G. Oehler, Carl Anthony Blau, Timothy S Martins, Niall Curley, Sylvia Chien, Jin Dai, Nicole Kauer, Ka Yee Yeung, Ling-Hong Hung, Cody Hammer, Paul C. Hendrie, Mary-Elizabeth M. Percival, Ryan D. Cassaday, Bart L. Scott, Roland B. Walter, Kelda Gardner, Mary Gwin, Heather Smith, Andrew Carson, Bradley Patay, Elihu H. Estey
Journal: Blood (2019)
Manufacture and In Vivo Support of Gene-Edited, Regulatory-like, T-Cells (edTreg) Using a Synthetic IL2 Receptor
Authors: Gene I. Uenishi, Cornell Mallari, Luis Gamboa, Samuel West, Chester Jacobs, Noelle Dahl, Greg Boucher, Samantha Chin, Rangoli Aeran, Dariusz Wodziak, Simon Gebremeskel, Karen Vo, Cade E. Ito, Laura Smith, Chandra Patel, Keith Abe, Basha Stankovich, Karen Sommer, Troy R. Torgerson, David J. Rawlings, Andrew M. Scharenberg, Greg J. Cost
Journal: Blood (2019)
The Binding of CD38 Therapeutics to Red Blood Cells and Platelets Subverts Depletion of Target Cells
Authors: Eric Robert Fedyk, Neeraja Idamakanti, Jia Chen, Jose Estevam, Vivian Hernandez, Matthew Wagoner, Mary Carsillo, Deborah Berg, Kristina Allikmets, Gezim Lahu, Antonio Palumbo
Journal: Blood (2019)
Role of DNA-PKcs/topoisomerase I interaction in the cellular sensitivity to S-phase-induced DNA damaging agents.
Authors: Michel Tautu, Daniele Montaudon, Komaraiah Palle, Noritaka Adachi, Marie Dutreix, Mary-Ann Bjornsti, Philippe Pourquier
Journal: Cancer Research (2008)

5779  Topoisomerase I (Top1) is a nuclear enzyme involved in the removal of torsional constraints associated with DNA replication and transcription. It cleaves the DNA on one strand and forms covalent top1-DNA cleavage complexes which are the target of top1 inhibitors such as camptothecins (CPT) and its analogs which are widely used in the treatment of human cancers. Cleavage complexes are not toxic per se but their conversion into irreversible DNA double-strand breaks (DSBs) lead to cell death. They result from the blockage of advancing replication forks by stabilized cleavage complexes. The precise mechanism of repair of Top1-mediated DSBs is not known, but probably involves various pathways including Homologous Recombination (HR) and Non-Homologous End-Joining (NHEJ). Previous studies have shown that M059J and CHO-V3 NHEJ-deficient cells were more sensitive than their NHEJ-proficient counterparts, MO59K and V3-F18. Because these cells lack DNA-PKcs (which associates to Ku70 and Ku86 to form DNA-PK), this effect was attributed to a defect in repair. Here, we show that CHO cells expressing a kinase dead-domain DNA-PKcs (V3-KA4) were not hypersensitive to CPT. This demonstrates for the first time that the absence of DNA-PKcs, but not the inhibition of its kinase activity, is responsible for the hypersensitivity of MO59J and V3 cells to CPT. Since Top1 was reported to interact with DNA-PKcs, we studied whether DNA-PKcs/Top1 interaction could be involved in the regulation of the cellular response to CPT. We show that Top1 interacts predominantly with the free form of DNA-PKcs in HeLa cells. This interaction was dramatically reduced when cells were treated by CPT and pre-treatment with the replication inhibitor aphidicolin could prevent the dissociation of Top1 from DNA-PKcs. Moreover, DNA-PK inhibits DNA relaxation and DNA cleavage catalyzed by purified Top1 in vitro. This inhibition depends on the presence of the N-terminus of Top1 since no effect was observed when the 70 kDa N-terminal truncated Top1 was used. Interestingly, we found that in untreated cells, absence of DNA-PKcs resulted in a higher amount of Top1-DNA cleavage complexes, as well as a higher DNA damage signalling as indicated by the increase in DSB formation, apoptosis levels, or p21 expression. We also show that in S-phase, the absence of DNA-PKcs could also sensitize cells to ionizing radiations. Altogether, our data shed light on a new potential role for DNA-PKcs, independent of its kinase activity and of NHEJ, where its interaction with Top1 regulates the cellular sensitivity to Top1 poisons and other DNA-damaging agents in S-phase.
CD3xCD19 Dart Treatment Is Efficient in Venetoclax Resistant CLL and Reverses T Cell Dysfunction
Authors: Anne W. J. Martens, Susanne R. Janssen, Ingrid A.M. Derks, Sanne Tonino, Eric Eldering, Gerritje J. W. van der Windt, Arnon P. Kater
Journal: Blood (2019)
An Allogeneic GM-CSF-Based Vaccine in Combination with Lenalidomide Induces Durable Remissions and Sustained Immunological Responses in Multiple Myeloma
Authors: Luca Biavati, Anna Ferguson, Carol Ann Huff, Lakshmi Rudraraju, Rachel Gittelman, Sarah Johnson, Catherine Sanders, Syed Abbas Ali, Kimberly Noonan, Ivan M. Borrello
Journal: Blood (2019)
Author’s response: influenza-associated mortality oseltamivir: beware of misstepping into stepwise procedures
Authors: Mark Reacher, Neville Q. Verlander, Maria Zambon
Journal: Eurosurveillance (2019)

Preview this article: Author's response: influenza-associated mortality oseltamivir: beware of misstepping into stepwise procedures, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/24/46/eurosurv-24-46-7-1.gif
Monocytic Myeloid-Derived Suppress Cells Restore Adipogenic Bone Marrow Microenvironment in Aplastic Anemia By Inhibiting Intra-BM CD8+ T Cells Proliferation
Authors: Ying Qu, Zhengxu Sun, Yan Yuan, Fen Wang, Kunpeng Wu, Yunfeng Cheng, Hua Jiang, Tong Chen
Journal: Blood (2019)
Effect of Avelumab to Immune Response in AML: A Phase I Study of Avelumab in Combination with Decitabine As First Line Treatment of Unfit Patients
Authors: Hong Zheng, Shin Mineishi, David F. Claxton, Junjia Zhu, Chenchen Zhao, Bei Jia, W. Christopher Ehmann, Seema Naik, Natthapol Songdej, Raymond J. Hohl
Journal: Blood (2019)
Newspaper Adherence to Media Reporting Guidelines for the Suicide Deaths of Kate Spade and Anthony Bourdain
Authors: Arielle H. Sheftall, Jaclyn L. Tissue, Paige Schlagbaum, Jonathan B. Singer, Nerissa Young, Jack H. Stevens, John P. Ackerman
Journal: JAMA Network Open (2019)

This cross-sectional study examines newspaper adherence to reporting guidelines for suicide after the deaths of Kate Spade and Anthony Bourdain.
Highly Efficient Multiplexed Base Editing with Minimized Off-Targets for the Development of Universal CAR-T Cells to Treat Pediatric T-ALL
Authors: Jason M Gehrke, Aaron Edwards, Ryan C. Murray, Amy Shaw, Yeh-Chuin Poh, Sarah Smith, Yi Yu, Nicole M. Gaudelli, Waseem Qasim, Giuseppe Ciaramella
Journal: Blood (2019)
Cost-effectiveness of ambulatory oxygen in improving quality of life in fibrotic lung disease: preliminary evidence from the AmbOx Trial
Authors: Jennifer A. Whitty, Jenny Rankin, Dina Visca, Vicky Tsipouri, Letizia Mori, Lisa Spencer, Huzaifa Adamali, Toby M. Maher, Nicholas S. Hopkinson, Surinder S. Birring, Morag Farquhar, Athol U. Wells, Piersante Sestini, Elisabetta A. Renzoni
Journal: European Respiratory Journal (2019)

<b>Ambulatory oxygen may be cost-effective in improving quality of life in fibrotic lung disease. To be more conclusive, we need to understand societal willingness to pay for quality of life improvements and whether improvements are sustained.</b>http://bit.ly/2pAiBJi
EXTH-58. INHIBITION OF DNA TOPOISOMERASE 1 AND POLY(ADP-RIBOSE) POLYMERASE SYNERGISTICALLY INDUCES CELL DEATH IN GLIOBLASTOMA WITH PTEN LOSS
Authors: Madison Butler, Yu-Ting Su, Lee Hwang, Laetitia Marzi, Mark Gilbert, Yves Pommier, Jing Wu
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma is known for its aggressive behavior and resistance to most available treatments. Topoisomerase 1 (Top1) functions by relaxing DNA supercoiling to facilitate replication. The novel Top1 inhibitor, LMP400, traps the enzyme and prevents its normal function, particularly in highly proliferative cells, resulting in DNA damage. Poly(ADP-ribose) polymerase (PARP) is involved in DNA repair responses triggered by Top1 inhibition. Phosphatase and tensin homolog (PTEN) loss, a frequent occurrence in glioblastoma, promotes DNA damage repair deficiency. We hypothesize that PTEN loss presents a vulnerability to combined induction of DNA damage and inhibition of repair mechanisms. METHODS Human glioblastoma cells were treated with LMP400 and/or Olaparib, a PARP inhibitor. Effects on cell proliferation and cell death were determined using a Beckman Coulter cell viability analyzer and colony formation assays. Synergism was calculated using COMPUSYN software. Cell cycle analysis was performed by FACS with EdU/DAPI staining, and Western blotting of lysate from drug-treated cells was performed to explore mechanisms of cytotoxicity. RESULTS LMP400 inhibited cell proliferation with an EC50 of 8.0 nM in U251 cells, and combination of LMP400 and Olaparib had a synergistic cytotoxic effect. Combination treatment enhanced activation of ATM-Chk2 and ATR-Chk1 pathways involved in DNA damage response signaling and increased S phase arrest. Increased protein expression of gamma-H2AX, cleaved caspase 3, and cleaved PARP was observed in combination-treated cells compared to single agents. Cell viability assays using isogenic glioblastoma cell lines with and without PTEN indicate that PTEN loss increases sensitivity to combination treatment. CONCLUSION Our results suggest that LMP400 and Olaparib combined treatment synergistically induces glioblastoma cell death, partially through inducing DNA damage, cell cycle arrest, and apoptosis. Mechanistic studies to investigate this vulnerability in glioblastoma with PTEN loss are ongoing. These results may lead to an effective personalized therapy for a molecularly defined subset of glioblastoma patients.
An Oral Combination Study of Novel Nucleoside Analogue Sapacitabine and BCL2 Inhibitor Venetoclax to Treat Patients with Relapsed or Refractory AML or MDS
Authors: Tapan M. Kadia, Gautam M. Borthakur, Elias Jabbour, Marina Y Konopleva, Farhad Ravandi, Courtney D. DiNardo, Daniella Zheleva, David Blake, Judy H Chiao
Journal: Blood (2019)