tbuckley/cabot-search huggingface dataset:
PDTM-05. SONIC HEDGEHOG SIGNALING PRIMES CEREBELLAR GRANULE NEURON PROGENITORS AND MEDULLOBLASTOMA CELLS FOR APOPTOSIS BY INDUCING PRO-APOPTOTIC BIM
Authors: Abigail Cleveland, Katherine Veleta, Timothy Gershon
Journal: Neuro-Oncology (2019)

Abstract Medulloblastomas, unlike other malignant brain tumors, are typically sensitive to radiation therapy (xRT). However, although xRT allows medulloblastoma patients to survive, it can also confer significant long term cognitive sequelae. Understanding the mechanisms of radiation sensitivity in medulloblastoma may identify ways to increase this sensitivity through targeted therapy. Cerebellar granule neuron progenitors (CGNPs), the cells of origin for SHH-subgroup medulloblastoma, are also sensitive to xRT. We have shown that SHH signaling, which induces CGN proliferation and in excess can cause medulloblastoma, induces the pro-apoptotic protein BIM, resulting in increased radiation sensitivity. SHH-stimulated CGNPs show robust BIM expression, which is blocked by the SMO inhibitor vismodegib. CGNPs in BIM null mice show normal SHH-driven proliferation, but are markedly less sensitive to radiation. Protein studies show that BIM binds to the anti-apoptotic proteins BCL-xL and MCL-1, suggesting a mechanism for increasing the sensitivity to radiation by lowering the apoptotic threshold. On-going studies will determine whether BIM is required for radiation sensitivity in SHH-driven medulloblastoma. If validated, the BIM interactions with BCL-xL and MCL-1 may be novel mechanisms to be targeted to improve medulloblastoma therapy.
The Effects of Text Messaging for Promoting the Retention of the First-Time Blood Donors, a Randomized Controlled Study (TEXT study)
Authors: Chontara Pongsananurak, Lalita Norasetthada, Adisak Tantiworawit, Ekarat Rattarittamrong, Thanawat Rattanathammethee, Maitree Sriwichai, Nipapan Leetrakool, Pokpong Piriyakhuntorn, Sasinee Hantrakool, Chatree Chai-Adisaksopha
Journal: Blood (2019)
RUNX1 Mutation Is Associated with Poor Outcome in Patients with Acute Myeloid Leukemia Receiving Allogeneic Stem Cell Transplantation
Authors: Onyee Chan, Chetasi Talati, Hannah H Asghari, Jinming Song, Mohammad Hussaini, Andrew T Kuykendall, David A Sallman, Eric Padron, Rami S. Komrokji, Alan F. List, Jeffrey E. Lancet, Asmita Mishra, Kendra L. Sweet
Journal: Blood (2019)
Vemurafenib Has Potent Antitumor Activity in Patients with Relapsed/Refractory BRAF Mutant Hairy Cell Leukemia
Authors: Jae H Park, Stephen S. Chung, Young Rock Chung, Helen Won, Eunhee Kim, Alan Saven, Martha Wadleigh, Richard M. Stone, Jacqueline C. Barrientos, Kanti R. Rai, Michael R. Grever, Jessica K. Altman, Mario E Lacouture, Neal Rosen, Michael Berger, Ross L Levine, Omar Abdel-Wahab, Martin S. Tallman
Journal: Blood (2014)
Combination of Four Drugs for Bloodstream Infection Caused By Carbapenem-Resistant Enterobacteriaceae in Severe Agranulocytosis Patients after Hematopoietic Stem Cell Transplantation
Authors: Yaqun Hong, Xiaofan Li, Xianling Chen, Ping Chen, Meiling Chen, Yiting Wang, Zhenshu Xu, Nainong Li
Journal: Blood (2019)
Early Intervention with Hypomethylating Agents in Transfusion-Independent Patients with Myelodysplastic Syndrome
Authors: Kelly S. Chien, Mahesh Swaminathan, Elias Jabbour, Farhad Ravandi, Tapan M. Kadia, Gautam M. Borthakur, Nicholas J. Short, Kelly Soltysiak, Sherry A. Pierce, Jane Waukau, Darla Miller, Jorge E. Cortes, Yesid Alvarado, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2019)
Ruxolitinib Reverses Checkpoint Inhibition By Downregulating PD-L1 and PD-L2 Expression on Both Tumor and Stromal Cells in Multiple Myeloma
Authors: Haiming Chen, Mingjie Li, Eric Sanchez, Nicole Ng, Erin Yu, Sean Bujarski, Zhengyi Yin, Tara Hekmati, Dylan Field, Jasper Wang, Isabella Nassir, Janna Yu, Justin Huang, David Daniely, Cathy S. Wang, Ning Xu, James R. Berenson
Journal: Blood (2019)
A Phase 3 Study of Eltrombopag Vs. Standard First-Line Management for Newly Diagnosed Immune Thrombocytopenia in Children
Authors: Kristin A. Shimano, Rachael F. Grace, Carolyn M. Bennett, Robert J Klaassen, Cindy Neunert, Ellis J. Neufeld, Clement Ma, Wendy B. London, Jenny M. Despotovic
Journal: Blood (2019)
Perioperative Bleeding Risk Assessment in a Cohort of Children with Low Levels of Von Willebrand Factor
Authors: Berardino Pollio, Maria Messina, Irene Ricca, Mauro Pagliarino, Ugo Ramenghi, Antonio Coppola, Anna Castiglione, Giovannino Ciccone, Teresa Ceglie, Anna Mondino, Paolo Tavormina, Claudia Linari
Journal: Blood (2019)
Efficacy of Allogeneic Hematopoietic Cell Transplantation (HCT) in Sickle Cell Disease: Results of a Systematic Review/Meta-Analysis
Authors: Madiha Iqbal, Tea Reljic, Ernesto Ayala, Hemant S. Murthy, Ambuj Kumar, Mohamed A Kharfan-Dabaja
Journal: Blood (2019)
Perception of Dementia Risk and Preventive Actions Among US Adults Aged 50 to 64 Years
Authors: Donovan T. Maust, Erica Solway, Kenneth M. Langa, Jeffrey T. Kullgren, Matthias Kirch, Dianne C. Singer, Preeti Malani
Journal: JAMA Neurology (2019)

ence in the female predominance in adults with AQP4-IgG compared with MOG-IgG.Together, these sex differences and the greater detection of MOG-IgG, especially in children, suggests that central demyelinating diseases associated with these biomarkers may have different drivers of autoimmunity.The rare coexistence of these 2 antibody biomarkers also points to distinct immunopathogeneses of these diseases.It has been postulated that MOG-IgG is an epiphenomenon, occurring with exposure of antigen in the AQP4-IgG disease.However, the rarity of dual positivity is this large cohort is evidence against an epiphenomenon.All individuals with dual positivity had high titers of AQP4-IgG and low titers of MOG-IgG, suggesting the disease phenotype may be more compatible with AQP4-IgG-positive neuromyelitis optica spectrum disorders.These findings suggest that MOG-IgG may occur more frequently than AQP4-IgG in patients tested for central demyelinating diseases, particularly in children.However, because the study population was derived from patients who had undergone a central demyelinating disease serological evaluation, these data should not be interpreted as representing seroprevalence in the general population.Further populationbased studies are required to determine the prevalence and incidence of MOG-IgG-associated disorders.
Ibrutinib in Combination with Venetoclax Decreases Mitochondrial Bioenergetics through the Impaired BTK, AKT and AMPK/SIRT/PGC-1α Signaling Pathway in CLL
Authors: Subir Roy Chowdhury, Amandeep Singh, Edwin Nguyen, Aaron Marshall, James B. Johnston, Spencer Bruce Gibson, Versha Banerji
Journal: Blood (2019)
End-of-Treatment 18[F]-FDG PET Can Predict Progression-Free Survival in Patients Undergoing Bendamustine + Rituximab for First Relapsed/Recurrent Follicular Lymphoma: The Result of W- J H S NHL01 Study
Authors: Shinya Rai, Koji Kato, Junji Suzumiya, Koji Izutsu, Momoko Nishikori, Hirohiko Shibayama, Yoshinobu Maeda, Kenichi Yoshimura, Ukihide Tateishi, Toshihiro Miyamoto, Jun Ishikawa, Tsutomu Takahashi, Takahiro Yamauchi, Koichi Akashi, Yuzuru Kanakura
Journal: Blood (2019)
Personal Use of Drug Samples by Physicians and Office Staff
Authors: Ajit P. Limaye
Journal: JAMA (1997)

<h3>To the Editor.</h3> —Dr Westfall and colleagues<sup>1</sup>raised ethical concerns regarding the frequent personal use of drug samples by medical personnel. We report on<i>Clostridium difficile</i>—related diarrhea as a complication of this practice in medical house staff who have ready access to pharmaceutical samples of antibiotics and frequent exposure to the organism in the hospital setting. A 26-year-old, otherwise healthy medical resident with self-diagnosed sinusitis began a course of amoxicillin-clavulanate samples that he had received from a pharmaceutical company representative. Ten days later he experienced crampy abdominal pain and watery diarrhea. He suspected<i>C difficile</i>—related diarrhea and empirically began a course of metronidazole until stool studies demonstrated<i>C difficile</i>by toxin assay (cultures for enteric pathogens were negative). His diarrhea responded to 10 days of oral metronidazole, but he experienced a relapse 4 weeks later that also responded promptly to re-treatment with the same regimen. A 28-year-old, otherwise
Single Cell Transcriptomic Analysis of the Histone H3 K27M Mutation in Pre-Leukemic Hematopoietic Stem Cells
Authors: Meaghan Boileau, Selin Jessa, Samantha Worme, Damien Faury, Nada Jabado, François Mercier, Claudia Kleinman, Kolja Eppert
Journal: Blood (2019)
PATH-42. IDH-MUTANT LOWER-GRADE ASTROCYTOMAS CAN BE STRATIFIED FOR RISK BY CDKN2A, CDK4 AND PDGFRA COPY NUMBER ALTERATIONS
Authors: Ryan Rui Yang, Kay Ka-Wai Li, Ho-Keung Ng
Journal: Neuro-Oncology (2019)

Abstract In the 2016 WHO classification of tumors of the CNS, isocitrate dehydrogenase (IDH) mutation is a main classifier for lower-grade astrocytomas and IDH mutated astrocytomas is now regarded as a single group with good prognosis. However, the molecular and clinical heterogeneity among IDH-mutant lower-grade astrocytomas have only rarely been investigated. In this study, we recruited 161 IDH-mutant lower-grade astrocytomas, and examined PDGFRA amplification, CDKN2A deletion, and CDK4 amplification by FISH analysis, TERT promoter mutation by Sanger sequencing, and ATRX loss and p53 expression by immunohistochemistry. We identified PDGFRA amplification, CDKN2A deletion, and CDK4 amplification in 18.6%, 14.9%, and 18.0% of our cohort respectively, and these alterations occurred in a mutually exclusive fashion. PDGFRA amplification was associated with shorter PFS (p&lt; 0.0001) and OS (p&lt; 0.0001). In tumors without PDGFRA amplification, CDKN2A deletion was associated with a shorter PFS (p=0.0332). Tumors were then divided into three risk groups based on the presence of molecular alterations: high-risk (PDGFRA amplification), intermediate-risk (CDKN2A deletion or CDK4 amplification) and low-risk (neither CDKN2A deletion, CDK4 amplification nor PDGFRA amplification). These three risk groups were significantly different in overall survival with mean survivals of 40.2, 62.9, and 71.8 months. The high-risk group also demonstrated a shorter PFS compared to intermediate- (p=0.036) and low-risk (p&lt; 0.0001) groups. Our data illustrate that IDH-mutant lower-grade astrocytomas is not a homogeneous group and should be molecularly stratified for risk.
Cost Analysis of Stored Autologous Peripheral Blood Stem Cells for a Second Autologous Transplantation in Multiple Myeloma Patients: A Markov Model
Authors: Anca Prica, Vinita Dhir, Nuchanan Areethamsirikul, Christine Chen, Donna Reece, Suzanne Trudel, Rodger Tiedemann, Vishal Kukreti
Journal: Blood (2016)
Proteomic Analysis of Mitochondrial Membrane Protein FAM210B in Erythroid Cells
Authors: Chie Suzuki, Tohru Fujiwara, Hiroki Shima, Koya Ono, Kei Saito, Noriko Fukuhara, Yasushi Onishi, Hisayuki Yokoyama, Shinichi Fujimaki, Yukio Nakamura, Hideo Harigae
Journal: Blood (2019)
Emotional Reactions to Disfigurement from Cancer Therapy
Authors: C A ADSETT
Journal: JAMA (1963)

Disfigurement not only produces current anxieties but reactivates childhood conflicts. The emotional reaction depends upon the disturbance to the patient's major adaptations to life as well as the meaning of the organ to the patient. Fear of isolation and rejection by others may be more terrifying than fear of death. Emotional reactions include regression with marked dependency, anxiety, depression, hostility and, if severe, paranoid states, hypochondriasis, denial, counterphobic behaviour, obsessive-compulsive reactions and schizophrenic reactions. Management basically involves early establishment of a positive doctor-patient relationship. In such a relationship the physican should educate his patient, undercut guilt, accept transient regression and expression of anger, set limits on counterphobic behaviour, either support or gently question denial of reality, and support, without being overly sympathetic, a depressed patient. The nurse, social worker, psychiatrist and the patient's family may be valuable members of the therapy team. Disfigurements of various body areas pose individual problems of management.
<i>Notes from the Field</i>: Unexplained Dermatologic, Respiratory, and Ophthalmic Symptoms Among Health Care Personnel at a Hospital — West Virginia, November 2017–January 2018
Authors: Todd J. Lucas, Mark Holodniy, Marie A. de Perio, Kiran M. Perkins, Isaac Benowitz, David Jackson, Ian Kracalik, Michael Grant, Gina Oda, Krista M. Powell
Journal: MMWR Morbidity and Mortality Weekly Report (2019)
Efficacy and Safety of Daratumumab, Bortezomib, and Dexamethasone (D-Vd) Versus Bortezomib and Dexamethasone (Vd) in First Relapse Patients (pts) with Multiple Myeloma (MM): Four-Year Update of Castor
Authors: Katja C. Weisel, Pieter Sonneveld, Maria-Victoria Mateos, Vania T.M. Hungria, Andrew Spencer, Jane Estell, Wolney G Barreto, Paolo Corradini, Chang-Ki Min, Eva Medvedova, Maria Krevvata, Sonali Trivedi, Xiang Qin, Huiling Pei, Jon Ukropec, Rachel Kobos, Ming Qi, Ajay K Nooka
Journal: Blood (2019)
The density and spatial tissue distribution of CD8+ and CD163+ immune cells predict response and outcome in melanoma patients receiving MAPK inhibitors
Authors: Daniela Massi, Eliana Rulli, Mara Cossa, Barbara Valeri, Monica Rodolfo, Barbara Merelli, Francesco De Logu, Romina Nassini, Michele Del Vecchio, Lorenza Di Guardo, Roberta De Penni, Michele Guida, Vanna Chiarion Sileni, Anna Maria Di Giacomo, Marco Tucci, Marcella Occelli, Francesca Portelli, Viviana Vallacchi, Francesca Consoli, Pietro Quaglino, Paola Queirolo, Gianna Baroni, Fabrizio Carnevale-Schianca, Laura Cattaneo, Alessandro Minisini, Giuseppe Palmieri, Licia Rivoltini, Mario Mandalà
Journal: Journal for ImmunoTherapy of Cancer (2019)

Clinical response to MAPK inhibitors in metastatic melanoma patients is heterogeneous for reasons still needing to be elucidated. As the patient immune activity contributes to treatment clinical benefit, the pre-existing level of immunity at tumor site may provide biomarkers of disease outcome to therapy. Here we investigated whether assessing the density and spatial tissue distribution of key immune cells in the tumor microenvironment could identify patients predisposed to respond to MAPK inhibitors.Pretreatment tumor biopsies from a total of 213 patients (158 for the training set and 55 for the validation set) treated with BRAF or BRAF/MEK inhibitors within the Italian Melanoma Intergroup were stained with selected immune markers (CD8, CD163, β-catenin, PD-L1, PD-L2). Results, obtained by blinded immunohistochemical scoring and digital image analysis, were correlated with clinical response and outcome by multivariate logistic models on response to treatment and clinical outcome, adjusted for American Joint Committee on Cancer stage, performance status, lactate dehydrogenase and treatment received.Patients with high intratumoral, but not peritumoral, CD8+ T cells and concomitantly low CD163+ myeloid cells displayed higher probability of response (OR 9.91, 95% CI 2.23-44.0, p = 0.003) and longer overall survival (HR 0.34, 95% CI 0.16-0.72, p = 0.005) compared to those with intratumoral low CD8+ T cells and high CD163+ myeloid cells. The latter phenotype was instead associated with a shorter progression free survival (p = 0.010). In contrast, PD-L1 and PD-L2 did not correlate with clinical outcome while tumor β-catenin overexpression showed association with lower probability of response (OR 0.48, 95% CI 0.21-1.06, p = 0.068).Analysis of the spatially constrained distribution of CD8+ and CD163+ cells, representative of the opposite circuits of antitumor vs protumor immunity, respectively, may assist in identifying melanoma patients with improved response and better outcome upon treatment with MAPK inhibitors. These data underline the role of endogenous immune microenvironment in predisposing metastatic melanoma patients to benefit from therapies targeting driver-oncogenic pathways.
EXTH-08. REPLACEMENT OF MICROGLIA BY BRAIN-ENGRAFTED MACROPHAGES PREVENTS MEMORY DEFICITS AFTER THERAPEUTIC WHOLE-BRAIN IRRADIATION
Authors: Xi Feng, Sonali Gupta, David Chen, Zoe Boosalis, Sharon Liu, Nalin Gupta, Susanna Rosi
Journal: Neuro-Oncology (2019)

Abstract Microglia have a distinct origin compared to blood circulating myeloid cells. Under normal physiological conditions, microglia are maintained by self-renewal, independent of hematopoietic progenitors. Following genetic or pharmacologic depletion, newborn microglia derive from the local residual pool and quickly repopulate the entire brain. The depletion of brain resident microglia during therapeutic whole-brain irradiation fully prevents irradiation-induced synaptic loss and recognition memory deficits but the mechanisms driving these protective effects are unknown. Here, we demonstrate that after CSF-1R inhibitor-mediated microglia depletion and therapeutic whole-brain irradiation, circulating monocytes engraft into the brain and replace the microglia pool. These monocyte-derived brain-engrafted macrophages have reduced phagocytic activity compared to microglia from irradiated brains, but similar to locally repopulated microglia without brain irradiation. Transcriptome comparisons reveal that brain-engrafted macrophages have both monocyte and embryonic microglia signatures. These results suggest that monocyte-derived brain-engrafted macrophages represent a novel therapeutic avenue for the treatment of brain radiotherapy-induced cognitive deficits.
Trends in Obesity Among Low-Income Young Children
Authors: Norbert Stefan, Matthias B. Schulze
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
EASIX for prediction of survival in lower-risk myelodysplastic syndromes
Authors: Almuth Merz, Ulrich Germing, Guido Kobbe, Jennifer Kaivers, Anna Jauch, Aleksandar Radujkovic, Manuela Hummel, Axel Benner, Maximilian Merz, Peter Dreger, Thomas Luft
Journal: Blood Cancer Journal (2019)

Abstract Patients with myelodysplastic syndromes (MDS) are at risk of early death from cardiovascular complications due to the link between clonal hematopoiesis and endothelial dysfunction. EASIX (Endothelial Activation and Stress Index) has been established to predict endothelial complications after allogeneic transplantation. We investigated the impact of EASIX measured at first diagnosis on survival of patients with lower- and higher-risk MDS (no allogeneic transplantation) in two independent institutions: n = 192 (training cohort) and n = 333 (validation cohort). Serum markers of endothelial cell distress were measured and correlated to EASIX. While no effects of EASIX on survival were observed in higher-risk patients, EASIX was associated with shorter survival in patients with lower-risk MDS in both cohorts (univariate: Cohort I: hazard ratio (HR): 1.46; 95% confidence interval (CI) 1.24–1.71; p -value &lt; 0.001/Cohort II: HR 1.31 [1.17–1.48]; p -value &lt; 0.001). Multivariate Cox regression analysis and prediction error analyses confirmed that EASIX remained a significant predictor of survival after adjustment for age, sex, cytogenetic abnormalities and bone marrow blasts in lower-risk patients. The model of the training cohort could be validated. Serum levels of Angiopioetin-2 correlated significantly with EASIX. We introduce EASIX as an easily accessible and independent predictor for survival in patients with lower-risk MDS.
Biochemical heterogeneity of ovarian cancer cells affects their sensitivity to docetaxel
Authors: Jerry Saunders, Kattron Cofield, Mary Kearns, Brigitte Miller, Larry W. Daniel
Journal: Cancer Research (2004)

5610  Tumor cell heterogeneity among ovarian cancers may be a significant factor in their response to chemotherapy. Many ovarian cancers lack functional PTEN, a tumor suppressor that antagonizes signaling through the PI3 kinase and Akt pathway. We have compared ovarian cancer cell lines and find that SKOV3 has abundant phosphorylated Akt while CaOV3 has very low levels of phosphorylated Akt. Both cell lines have comparable levels of total Akt. Conversely, CaOV3 cells have high levels of PTEN and phosphorylated PTEN compared to SKOV3 cells. For comparison we evaluated a cervical cancer cell line and found that CaSki cells, like SKOV3, had high levels of phosphorylated Akt but low levels of PTEN. Therefore, these cells represent the marked biochemical heterogeneity possible among gynecological tumors. The CaOV3 cells which have active PTEN were more sensitive to docetaxel (IC50 = 3.7 nM) than were SKOV3 (IC50 = 12.2 nM) or CaSki (IC50 = 9.2 nM). To determine if inhibiting the Akt pathway would increase the sensitivity of the cells to docetaxel we used the PI3-kinase inhibitor LY294002 in combination. LY294002 inhibited the growth of all three cell lines (IC50 = 10 μM). In combination, LY294002 increased the effectiveness of docetaxel in the cell lines which had an intact Akt signaling pathway (SKOV3 and CaSki). However, in CaOV3 the combination of docetaxel with LY294002 was significantly less effective than LY294002 alone. These data indicate the potential effects of the heterogeneity of cancer cells on their response to docetaxel and indicate the need for individualized selection of combination chemotherapy based upon the phenotype of the tumor.