tbuckley/cabot-search huggingface dataset:
Associations of eczema phenotypes with emotional and behavioural problems from birth until school age. The Generation R Study
Authors: C. Hu, T. Nijsten, S.G.M.A. Pasmans, J.C. Jongste, P.W. Jansen, L. Duijts
Journal: British Journal of Dermatology (2019)

Eczema phenotypes and emotional and behavioural problems are highly prevalent in childhood, but their mutual relationship is not fully clear.To examine the associations of eczema phenotypes with school-age emotional and behavioural problems, and the bidirectional associations of eczema and emotional and behavioural problems from birth until 10 years.This study among 5265 individuals was embedded in a prospective population-based cohort study. Never, early transient, mid-transient, late transient and persistent eczema phenotypes were identified based on parent-reported, physician-diagnosed eczema from age 6 months until 10 years. Emotional (internalizing) and behavioural (externalizing) problems were measured repeatedly using the Child Behavior Checklist from age 1·5 to 10 years. Cross-lagged models were applied for bidirectional analyses.All eczema phenotypes were associated with more internalizing problems and attention problems at age 10 years, compared with never having eczema: range of Z-score differences 0·14 [95% confidence interval (CI) 0·01-0·27] to 0·39 (95% CI 0·18-0·60). Children with early transient eczema had more aggressive behaviour symptoms at age 10 years (Z = 0·16, 95% CI 0·05-0·27). Bidirectional analysis showed that eczema at 0-2 years was associated with more internalizing and externalizing problems at ages 3-6 and 10 years, while, inversely, only internalizing problems at 0-2 years were associated with an increased risk of eczema at age 10 years.Eczema phenotypes are very modestly associated with more somatic symptoms and attention problems at school age. Early transient eczema is associated with more aggressive behaviour symptoms. Directional effects seem to occur from early-life eczema to later-life internalizing and externalizing problems, rather than the reverse.
The Effect of Age and CD34+ Stem Cell Dose on Autologous Hematopoietic Stem Cell Transplantation Outcomes in Multiple Myeloma - Single Institution Experience
Authors: Madeline Skousen, Sarah A. Holstein, Matthew A. Lunning, Elizabeth R. Lyden, Gilmore Sheree, Kimberly Schmit-Pokorny, James O. Armitage, Zaid S. Al-Kadhimi, Julie M Vose, Muhamed Baljevic
Journal: Blood (2019)
Percutaneous Transhepatic Cholangiography
Authors: STEVEN BROZINSKY
Journal: Annals of Internal Medicine (1977)

Letters and Corrections1 December 1977Percutaneous Transhepatic CholangiographySTEVEN BROZINSKY, M.D., ELIAS PUROW, M.D., SAUL J. GROSBERG, M.D.STEVEN BROZINSKY, M.D.Search for more papers by this author, ELIAS PUROW, M.D.Search for more papers by this author, SAUL J. GROSBERG, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-87-6-795_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We, too, are impressed with the diagnostic yield and low morbidity of percutaneous transhepatic cholangiography with the Chiba needle as described by Pereiras and colleagues (Ann Intern Med 86:562-568, 1977). However, their paper raises some important questions.1. The success rate of (95.6%) of entering nondilated systems is considerably greater than in previous reports (56% to 89%) (1-3). Assuming the same degree of competence existed, one wonders whether their increased success was due to excessive passes into the liver. They state that "if after seven passes the biliary tree is not visualized, it is assumed that we...References1. BURCHARTHNIELBO FN: Percutaneous transhepatic cholangiography with selective catheterization of the common bile duct. Am J Roentgenol 127:409-412, 1976 CrossrefMedlineGoogle Scholar2. REDEKERKARVOUNTZISRICHMANHORISAWA AGRM: Percutaneous transhepatic cholangiography. An improved technique. JAMA 231:386-387, 1975 CrossrefMedlineGoogle Scholar3. PEREIRASWHITEDUSOLIRWINHUTSONLIEBERMANSCHIFF RPMGDBE: Percutaneous transhepatic cholangiography utilizing the Chiba University needle. Radiology 121:219-221, 1976 CrossrefMedlineGoogle Scholar4. RABB R: The use of antibiotics in biliary tract disease. Am J Gastroenterol 63:37-39, 1975 MedlineGoogle Scholar1. FERUCCIWITTENBERG JJ: Refinements in Chiba needle transhepatic cholangiography. Am J Roentgenol 129:11, 1977 CrossrefMedlineGoogle Scholar2. GREENWALDPEREIRASMORRISSCHIFF RRME: Jaundice, choledocholithiasis, and a non-dilated common duct. Submitted for publication Google Scholar3. KEIGHLEYDRYSDALEQUORAISHIBURDONALEXANDER-WILLIAMS MRADJ: Antibiotics in biliary disease: the relative importance of antibiotic concentrations in the bile and serum. Gut 17:495-500, 1976 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Brooklyn Veterans Administration Hospital Brooklyn, NY 11203 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1977Volume 87, Issue 6Page: 795-796KeywordsBiliary systemLiverMorbidity Issue Published: 1 December 1977 PDF DownloadLoading ...
CSIG-27. PRC2-INDEPENDENT FUNCTION OF EZH2/HP1BP3 COMPLEX IN GLIOMA STEM CELLS
Authors: Junxia Zhang, Tianfu Yu, Ning Liu
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma (GBM) displays cellular and genetical heterogeneity harboring a subpopulation of glioma stem cells (GSCs). Enhancer of zeste homolog 2 (EZH2), a histone lysine methyltransferase, is the core subunit of the polycomb repressor 2 (PRC2) complex, mediates gene transcriptional repression in both normal and tumor stem cells. An oncogenic role of EZH2 as a PRC2-dependent transcriptional silencer is well established; however, non-canonical functions of EZH2 are incompletely understood. Here we found a novel oncogenic mechanism for EZH2 in a PRC2-indenpend way in GSCs. Using HPLC-MS/MS and IP assay, EZH2 bound to HP1BP3 (heterochromatin protein 1 binding protein 3), a heterochromatin-related protein, with its pre-SET domain. Overexpression of H1P3B3 enhanced the proliferation, self-renewal and temozolomide (TMZ) resistance of GBM cells. Intriguingly, H1PBP3 was up-regulated in high grade gliomas with proneural (PN) subtypes and had a high predictive value on prognosis in patients with PN gliomas. Furthermore, EZH2 and HP1BP3 co-activated the expression of WNT7B by blocking the methylation of H3K9, thereby increasing TMZ resistance and tumorigenicity of glioblastoma cells. Interestingly, inhibition of WNT7B autocrine via LGK974, a specific porcupine inhibitor, effectively reversed the TMZ resistance of both GSCs and GBM glioma cells expressing HP1BP3. Hence, targeting the PRC2-independent function of EZH2 is an effective approach to enhance the efficacy of treating GBM.
Final Results of Prospective Treatment with Pegylated Interferon Alfa-2a for Patients with Polycythemia Vera and Essential Thrombocythemia in First and Second-Line Settings
Authors: Abdulraheem Yacoub, John Mascarenhas, Ruben A. Mesa, Heidi E. Kosiorek, Raajit K. Rampal, Richard T. Silver, Mohamed E. Salama, Olivia Siwoski, Amylou C. Dueck, Lonette Sandy, Mary Frances McMullin, Joanne Ewing, Casey L. O'Connell, Adam J. Mead, Valerio De Stefano, Rona Singer Weinberg, Maria R. Baer, Craig M. Kessler, Elliott F. Winton, Alessandro M. Vannucchi, Marina Kremyanskaya, Joseph Vadakara, Vittorio Rosti, Elizabeth O. Hexner, Damiano Rondelli, Murat O. Arcasoy, Alessandro Rambaldi, Ellen K. Ritchie, Tiziano Barbui, Jean-Jacques Kiladjian, Claire N Harrison, Josef T. Prchal, Ronald Hoffman
Journal: Blood (2019)
Association of Bleeding Severity with Mortality with Extended Thromboprophylaxis in the Medically Ill in the Mariner Trial
Authors: Alex C. Spyropoulos, Walter Ageno, Gregory W. Albers, C. Gregory Elliott, Jonathan L. Halperin, William R. Hiatt, Gregory Maynard, P. Gabriel Steg, Jeffrey I. Weitz, Theodore E. Spiro, Wentao Lu, Chiara Sugarmann, Concetta Lipardi, Gary E. Raskob, Elliot S. Barnathan
Journal: Blood (2019)
An Increased Bone Mineral Density As an Adverse Prognostic Factor in Patients with Systemic Mastocytosis
Authors: Mohamad Jawhar, Juliana Schwaab, Nicole Naumann, Georgia Metzgeroth, Alice Fabarius, Stefan O Schoenberg, Wolf-Karsten Hofmann, Philipp Riffel, Andreas Reiter
Journal: Blood (2019)
Subcutaneous Bortezomib, Thalidomide and Dexamethasone As Induction Therapy Prior to Autologous Peripheral Blood Stem Cell Transplantation in Young Patients Diagnosed of Multiple Myeloma. a Retrospective Analysis from Two Centers
Authors: David Jiménez Ruiz De La Torre, Gladys Ibarra, Maite Encuentra, Laura Abril, Albert Oriol, Josep-Maria Ribera, Anna Sureda
Journal: Blood (2019)
NCOG-10. RELATIONSHIP BETWEEN COGNITIVE FUNCTION, MOOD, AND FUNCTIONING IN GLIOMA SURVIVORS
Authors: Kathleen Van Dyk, Brandon F Heimberg, Justin Choi, Catalina Raymond, Chencai Wang, Albert Lai, Timothy Cloughesy, Benjamin Ellingson, P Leia Nghiemphu
Journal: Neuro-Oncology (2019)

Abstract Ensuring optimal quality of life and functioning is a clinical priority in treating glioma survivors. Cognitive function and mood symptoms are prevalent in this population after treatment and it’s reasonable to consider these as significant contributors to patients’ functioning at work and in daily life. However, it’s unclear the degree to which these symptoms contribute to such outcomes. To address this question, we examined the relationships between cognitive tests (i.e., a neuropsychological battery) and mood measures (i.e., the Beck Depression Inventory-II, and the Beck Anxiety Inventory) and work and daily functioning (i.e., Work Productivity and Activity Impairment Questionnaire). Partial correlation of cognitive tests and regression models also included age and IQ (i.e., Test of Premorbid Functioning). Of the 11 participants who were currently working, worse work productivity was significantly associated with worse processing speed (Stroop color naming r=-.74,p=.03, Stroop color word r=-.78,p=.02). Similarly, worse ability in daily activities was also associated with worse processing speed and executive function (Stroop color naming, r=-.52,p=.04; Stroop color word, r=-.55,p=.03; Trails B, r=-.53,p=.03). Greater depression symptoms were strongly correlated with both worse work productivity (r=.83,p=.002), and worse ability in daily activities (r=.55,p=.01). Depression symptoms were generally uncorrelated with cognitive scores. In linear regression models that included both depression symptoms and cognitive scores, only depression emerged as a significant predictor of work productivity and ability to conduct daily activities. In sum, glioma survivors face multiple threats to work and daily functioning by way of tumor and treatment related symptoms. Our analyses suggest that both cognitive function and mood symptoms are important to consider in optimizing functioning, but depression appears to vastly outweigh cognitive function in this regard. These preliminary findings highlight the importance of careful attention to these symptoms in survivorship and point to future research directions elaborating on these relationships.
A Machine-Learning Approach Using PET-Based Radiomics to Predict the Histological Subtypes of Lung Cancer
Authors: Seung Hyup Hyun, Mi Sun Ahn, Young Wha Koh, Su Jin Lee
Journal: Clinical Nuclear Medicine (2019)

Purpose We sought to distinguish lung adenocarcinoma (ADC) from squamous cell carcinoma using a machine-learning algorithm with PET-based radiomic features. Methods A total of 396 patients with 210 ADCs and 186 squamous cell carcinomas who underwent FDG PET/CT prior to treatment were retrospectively analyzed. Four clinical features (age, sex, tumor size, and smoking status) and 40 radiomic features were investigated in terms of lung ADC subtype prediction. Radiomic features were extracted from the PET images of segmented tumors using the LIFEx package. The clinical and radiomic features were ranked, and a subset of useful features was selected based on Gini coefficient scores in terms of associations with histological class. The areas under the receiver operating characteristic curves (AUCs) of classifications afforded by several machine-learning algorithms (random forest, neural network, naive Bayes, logistic regression, and a support vector machine) were compared and validated via random sampling. Results We developed and validated a PET-based radiomic model predicting the histological subtypes of lung cancer. Sex, SUVmax, gray-level zone length nonuniformity, gray-level nonuniformity for zone, and total lesion glycolysis were the 5 best predictors of lung ADC. The logistic regression model outperformed all other classifiers (AUC = 0.859, accuracy = 0.769, F1 score = 0.774, precision = 0.804, recall = 0.746) followed by the neural network model (AUC = 0.854, accuracy = 0.772, F1 score = 0.777, precision = 0.807, recall = 0.750). Conclusions A machine-learning approach successfully identified the histological subtypes of lung cancer. A PET-based radiomic features may help clinicians improve the histopathologic diagnosis in a noninvasive manner.
Impact of Idelalisib Treatment Interruption with or without Dose Reduction on Outcomes in Relapsed / Refractory Indolent Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia
Authors: Shuo Ma, Rebecca J Chan, Lin Gu, Guan Xing, Nishan Rajakumaraswamy, Bianca Ruzicka, Nina D. Wagner-Johnston
Journal: Blood (2019)
Progressive Multifocal Leukoencephalopathy in a Patient with Multiple Myeloma Receiving Daratumumab and Pomalidomide
Authors: Jorge Monge, Jorge Contreras, Sarah Elsoukkary, Jin Guo, Art Perry, Robin S. Solomon, Kari Flicker, David S Jayabalan, Morton Coleman, Adriana C. Rossi, Rebecca Harris, Markus Plate, Joerg-Patrick Stuebgen, Ruben Niesvizky
Journal: Blood (2019)
PATH-26. CHARACTERIZING GENETIC DIFFERENCE IN CYSTIC GLIOBLASTOMA
Authors: Zhihua Chen, Xidai Long, Yifeng Miao, Xuan Zhou, Russell Rockne
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma (GBM) is characterized by widespread genetic and transcriptional heterogeneity. Cystic GBM (cGBM) as a rare type, yet the cause of cyst formation and their bioinformatics about the role of the epigenome in disease progression are still unknown. We believe that there are certain factors that cause the entity of tumor to dissolve, leading to the formation of cavities inside the tumor. Exploring the is mechanism and key gene targets may become important strategies for future treatment. Here, we present genome-scale maps of DNA methylation, WES and whole transcriptome sequence in matched cGBM and noncGBM, as well as MRI image digital analysis and immunology scales to investigate the difference between these two groups. Firstly, we find that they are totally two different groups by transcription start site (TSS) Upstream and downstream methylation distribution. When Cgbm VS NONCgbm, There are 220 sites are up-regulation and 6273 sites are down-regulation. Next, whole transcriptome Sequence result showed that 2934 differential mRNA are down-regulation and 4524 differential mRNA are up-regulation in cGBM group, compare with noncGBM. At the same time, 896 differential genes are down-regulation and 1044 differential genes are up-regulation in cGBM group; 1744 differential IncRNA are down and 1643 differential IncRNA are up. Finally, we didn’t find different novel gene on whole transcriptome sequence. This is the first time we detect the varieties between cGBM and noncGBM based on the realm of DNA methylation, WES and whole transcriptome sequence. The further analyses deserve to do to explain the formation of cyst in tumor and vital gene target, which could be benefit to new treatment decision.
EXTH-03. TRIPTOLIDE, A NOVEL THERAPEUTIC AGENT FOR IDH1-MUTATED GLIOMA
Authors: Di Yu, Yang Liu, Guowang Xu, Chunzhang Yang
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Isocitrate dehydrogenase (IDH1/2) mutations are common genetic abnormalities in human malignancies, which result in neomorphic enzyme activity that catalyzes 2-hydroxyglutarate (2-HG) production. While IDH mutations are recognized as critical cancer-associated genetic changes, the therapeutic options for IDH-mutated cancers remain limited. METHODS In the present study, we investigated the reactive oxygen species (ROS) scavenging pathways in patient-derived IDH1-mutated cells. Further, we investigated the protective role of glutathione de novo synthesis for IDH1-mutated cancer cells. Finally, we evaluated triptolide, a diterpenoid epoxide derived from Tripterygium wilfordii, as an experimental therapeutic for IDH1-mutated cells and xenografts. RESULTS We discovered that the neomorphic activity of IDH1 mutant enzyme triggers metabolic depletion and a substantial elevated burden of ROS scavenging in cancer cells. The nuclear factor erythroid 2-related factor 2 (NRF2)-guided antioxidant pathway plays a key role in maintaining redox homeostasis for IDH1-mutated cells. Triptolide serves as a potent inhibitor of NRF2 through enhancing the NRF2 ubiquitination and subsequently proteasomal degradation. Additionally, triptolide compromises the de novo synthesis of glutathione via suppression of NRF2-guided transcription of SLC7A11, which encodes cystine/glutamate transporter (xCT). Reduced availability of glutathione results in overwhelming oxidative damage in DNA and lipid, which translates into severe cytotoxicity and reduced xenograft expansion of IDH1-mutated cells. CONCLUSION Overall our findings highlight triptolide as a valuable synthetic lethality approach for IDH1-mutated malignancies by targeting NRF2-guided redox homeostasis.
Comparative Review of 30 Day Non-Relapse Mortality (NRM) in B-Cell Lymphomas Associated with Anti-CD19 Chimeric Antigen Receptor T-Cells (CAR-T) from FDA Database, Clinical Studies, and MD Anderson
Authors: Ethan Burns, Kartik Anand, Jason R. Westin, Sai Ravi Kiran Pingali, Joe Ensor, Dahlia Sano, Loretta J. Nastoupil, Hun Ju Lee, Yago Nieto, Issa F. Khouri, Felipe Samaniego, Simrit Parmar, Michael Wang, Misha Hawkins, Sherry Adkins, Luis E. Fayad, Raphael E Steiner, Ranjit Nair, Sairah Ahmed, Nathan H. Fowler, Sattva S Neelapu, Swaminathan P. Iyer
Journal: Blood (2019)
Dreamm-5: Platform Trial Evaluating Belantamab Mafodotin (a BCMA-directed Immuno-conjugate) in Combination with Novel Agents in Relapsed or Refractory Multiple Myeloma (RRMM)
Authors: Paul G. Richardson, Swethajit Biswas, Beata Holkova, Nicola Jackson, Thelma Netherway, Weichao Bao, Geraldine Ferron-Brady, Anne Yeakey, Chris Shelton, Rocio Montes De Oca, Chris Ahlers, Sonia Franco, Marc Ballas, Elaine Paul, Katarina Luptakova, Ira Gupta, Joanna Opalinska
Journal: Blood (2019)
Myelodysplastic Syndrome with Excess Blasts and Secondary Acute Myeloid Leukemia: Same Disease with Different Blast Count
Authors: Xueyan Chen, Megan Othus, Brent L Wood, Roland B. Walter, Pamela S. Becker, Mary-Elizabeth M. Percival, Janis L. Abkowitz, Frederick R. Appelbaum, Elihu H. Estey
Journal: Blood (2019)
ACTR-55. OPTIMIZED TREAT-RESECT-TREAT STUDY DESIGN FOR CONVECTION-ENHANCED DELIVERY OF A FIRST-IN-CLASS BIOLOGIC IN THE TREATMENT OF GLIOBLASTOMA
Authors: Amanda Immidisetti, Chibueze Nwagwu, W Shawn Carbonell, Anne-Marie Carbonell
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Development of effective treatments for high-grade glioma (HGG) including glioblastoma is hampered by 1) the blood brain barrier, 2) an infiltrative growth pattern, 3) rapid development of adaptive therapeutic resistance, and 4) dose-limiting toxicity due to systemic exposure. Novel therapeutics and delivery techniques are warranted to overcome these obstacles and meaningfully improve patient outcomes. OS2966 is the first ever clinical-ready therapeutic candidate against the adhesion receptor subunit, CD29/β1 integrin. CD29 is highly overexpressed in glioblastoma and has been shown to drive tumor progression, invasion, and resistance to multiple modalities of therapy including immunotherapies. Here, we present a novel phase I trial design addressing all four obstacles plaguing effective treatment of HGG, while also enabling biomarker development. STUDY DESIGN This 2-part, ascending concentration, phase I clinical trial will enroll patients with recurrent/progressive HGG requiring a clinically-indicated resection. In part 1, patients will undergo stereotactic tumor biopsy followed by placement of a purpose-built catheter which is used for intratumoral convection-enhanced delivery (CED) of OS2966. Subsequently, patients undergo their clinically-indicated tumor resection followed by CED of OS2966 to the surrounding tumor-infiltrated brain. Matched, pre- and post-infusion tumor specimens will be utilized for biomarker development and validation of target engagement by receptor occupancy. Dose escalation will be achieved using a unique concentration-based accelerated titration design. DISCUSSION The present study design leverages multiple innovations including: 1) the latest CED technology, 2) two-part design including neoadjuvant intratumoral administration, 3) a first-in-class investigational therapeutic, and 4) concentration-based dosing. A U.S. Food and Drug Administration (FDA) Investigational New Drug application (IND) for the above protocol is now active.
Molecular Correlates of Central Nervous System Relapse in Diffuse Large B-Cell Lymphoma
Authors: Robert Kridel, Keren Isaev, Daisuke Ennishi, Brian Skinnider, Karen Mungall, Andrew J. Mungall, Mehran Bakhtiari, Rosemarie Tremblay-Lemay, Barbara Meissner, Susana Ben-Neriah, Merrill Boyle, Diego Villa, Marco A. Marra, Christian Steidl, Randy D. Gascoyne, Kerry J Savage, David W. Scott
Journal: Blood (2019)
Epigenetic Priming with Decitabine Followed By Low-Dose Idarubicin Plus Cytarabine in AML Evolving from MDS or Higher Risk MDS: A Multicentre Phase 2 Single-Arm Trial
Authors: Hongyan Tong, Xinping Zhou, Chen Mei, Jin Zhang, Ying Lu, Jianping Lan, Shengyun Lin, Yuefeng Zhuang, Yuemin Kuang, Yanling Ren, Liya Ma, Juying Wei, Li Ye, Weilai Xu, Kongfei Li, Chenxi Lu, Jie Jin
Journal: Blood (2019)