tbuckley/cabot-search huggingface dataset:
Marijuana Use Among 10th Grade Students — Washington, 2014
Authors: Anar Shah, Mandy Stahre
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Some studies have suggested that long-term, regular use of marijuana starting in adolescence might impair brain development and lower intelligence quotient (1,2). Since 2012, purchase of recreational or retail marijuana has become legal for persons aged ≥21 years in the District of Columbia, Alaska, California, Colorado, Maine, Massachusetts, Nevada, Oregon, and Washington, raising concern about increased marijuana access by youths. The law taxing and regulating recreational or retail marijuana was approved by Washington voters in 2012 and the first retail licenses were issued in July 2014; medical marijuana use has been legal since 1998. To examine the prevalence, characteristics, and behaviors of current marijuana users among 10th grade students, the Washington State Department of Health analyzed data from the state's 2014 Healthy Youth Survey (HYS) regarding current marijuana use. In 2014, 18.1% of 10th grade students (usually aged 15-16 years) reported using marijuana during the preceding 30 days; of these students, 32% reported using it on ≥10 days. Among the marijuana users, 65% reported obtaining marijuana through their peer networks, which included friends, older siblings, or at a party. Identification of comprehensive and sustainable public health interventions are needed to prevent and reduce youth marijuana use. Establishment of state and jurisdiction surveillance of youth marijuana use could be useful to anticipate and monitor the effects of legalization and track trends in use before states consider legalizing recreational or retail marijuana.
124. Cas9-Mediated Genome Editing in Hematopoietic Stem/Progenitor Cells
Authors: Jennifer L. Gori, G. Grant Welstead, McKensie A. Collins, Justin W. Fang, Ari E. Friedland, David Bumcrot
Journal: Molecular Therapy (2015)

Transplantation of genetically modified autologous hematopoietic stem/progenitor cells (HSPCs) has proven to be an effective clinical treatment for patients with hematologic disease. Genome editing with the CRISPR/Cas9 platform has been shown to precisely alter endogenous gene targets in multiple human cell lines and animal models. Here, we compared Cas9-induced gene modification in primary human HSPCs, including mobilized peripheral blood and steady state bone marrow CD34+ cells. Co-delivery of Streptococcus pyogenes or Staphylococcus aureus Cas9 paired with locus-specific guide RNAs induced targeted gene editing in CD34+ cells and hematopoietic progeny, as determined by T7E1 assay and DNA sequence analysis. Multiple gene targets and delivery strategies were evaluated in these primary human CD34+ cells. Importantly, hematopoietic progeny differentiated from Cas9 gene-edited HSPCs maintained ex vivo hematopoietic colony forming potential. This study provides further evidence of Cas9-mediated genome editing in clinically relevant primary cell populations.
Phase 1 Clinical Trial of the Novel Structure Proteasome Inhibitor NPI-0052 in Patients with Relapsed and Relapsed/Refractory Multiple Myeloma (MM).
Authors: Paul Richardson, Craig Hofmeister, Andrzej Jakubowiak, Todd M. Zimmerman, Matthew A. Spear, Michael A. Palladino, Angie M. Longenecker, Susan L. Kelly, Saskia Neuteboom, Gillian F Cropp, G. Kenneth Lloyd, Alison L. Hannah, Kenneth C. Anderson
Journal: Blood (2009)
O040 : Heritability of hepatic fibrosis and hepatic steatosis, and their shared gene effects with metabolic traits in NAFLD: A prospective twin study
Authors: R. Loomba, N. Schork, C.-H. Chen, A. Bhatt, B. Ang, P. Nguyen, C. Hernandez, L. Richards, J. Salotti, S. Lin, K. Nelson, C.B. Sirlin, D. Brenner
Journal: Journal of Hepatology (2015)
Abstract 472: Galectin-3 modulates glioblastomas (GBM) tumor microenvironment, and is linked to glioblastoma invasion
Authors: Umadevi V. Wesley, Esat Resad, Paul Clark, Carolina Larrain, John Kuo, Robert J. Dempsey
Journal: Cancer Research (2015)

Abstract Malignant glioblastomas (GBM) are lethal form of brain tumors, and are difficult to treat due to their invasion into the brain parenchyma. Aggressive and invasive nature of GBM is at least partly attributable to GBM associated stem cells (GSC). Soluble factors released by GBM and GSC can recruit inflammatory cells, including brain resident microglia to tumor micro-environment (TME) that support angiogenesis and invasion. We have previously shown that exogenous Galectin-3 (Gal-3), a carbohydrate binding lectin increases the migratory potential of BV2 microglial cells, and promotes the formation of pro-angiogenic structures in an in vitro HUVEC culture and 3D matrigel model. Furthermore, Gal-3 supports the survival of microglial cells under hypoxic environment. In this study, we investigated the role of Gal-3 in GBM by utilizing the biochemical and molecular approaches. Using well characterized GBM tumor cell lines, and GSC lines that exhibit various degrees of invasive potential, we have identified that the expression of the Gal-3 is significantly up-regulated in GSCs that are highly invasive as compared to those that form only focal tumors in a mouse xenotransplantation model. Gal-3 is also highly expressed in microglia that accumulated in and around the GSC tumors in mouse brain, as indicated by co-localization of Gal-3 and Iba1, the maker for activated microglia. Furthermore, Gal-3 expression is significantly increased in GBM tumor cells when exposed to in vitro hypoxic conditions. Importantly, Gal-3 increased the migratory potential of GBM tumor cells in vitro, indicating its role as a chemo-attractant. Taken together, these results suggest that Gal-3 plays a critical role in promoting GBM invasion through modulating the interaction of microglia in TME and GBM. Thus Gal-3 may be a potential therapeutic target for GBM. Citation Format: Umadevi V. Wesley, Esat Resad, Paul Clark, Carolina Larrain, John Kuo, Robert J. Dempsey. Galectin-3 modulates glioblastomas (GBM) tumor microenvironment, and is linked to glioblastoma invasion. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 472. doi:10.1158/1538-7445.AM2015-472
CD70/CD27 signaling promotes blast stemness and is a viable therapeutic target in acute myeloid leukemia
Authors: Carsten Riether, Christian M. Schürch, Elias D. Bührer, Magdalena Hinterbrandner, Anne-Laure Huguenin, Sabine Hoepner, Inti Zlobec, Thomas Pabst, Ramin Radpour, Adrian F. Ochsenbein
Journal: The Journal of Experimental Medicine (2016)

Aberrant proliferation, symmetric self-renewal, increased survival, and defective differentiation of malignant blasts are key oncogenic drivers in acute myeloid leukemia (AML). Stem cell gene signatures predict poor prognosis in AML patients; however, with few exceptions, these deregulated molecular pathways cannot be targeted therapeutically. In this study, we demonstrate that the TNF superfamily ligand–receptor pair CD70/CD27 is expressed on AML blasts and AML stem/progenitor cells. CD70/CD27 signaling in AML cells activates stem cell gene expression programs, including the Wnt pathway, and promotes symmetric cell divisions and proliferation. Soluble CD27, reflecting the extent of CD70/CD27 interactions in vivo, was significantly elevated in the sera of newly diagnosed AML patients and is a strong independent negative prognostic biomarker for overall survival. Blocking the CD70/CD27 interaction by mAb induced asymmetric cell divisions and differentiation in AML blasts and AML stem/progenitor cells, inhibited cell growth and colony formation, and significantly prolonged survival in murine AML xenografts. Importantly, hematopoietic stem/progenitor cells from healthy BM donors express neither CD70 nor CD27 and were unaffected by blocking mAb treatment. Therefore, targeting CD70/CD27 signaling represents a promising therapeutic strategy for AML.
An Experimental Study on Drugs for Myocardial Infarction
Authors: Toshihiro Kobayakawa
Journal: Circulation (1972)

Myocardial infarction ranks high among the causes of death In adults and the establishment of its prophylactic measures and therapeutic means is one of the primary tasks assigned to today's medicine. In the pathogenesis of myocardial infarction, coronary atherosclerosis plays an important role. Many attempts have so far been made in order to prevent the progress of atherosclerosis, but none of them have led to a directly effective therapeutic means for myocardial infarction. Therefore, the improvement of oxygen supply has been tried through increasing endocardial blood supply. Once coronary sclerosis is established, however, blood flow is not expected to be improved beyond a limited extent. It may be advisable to take a different approach to prevent myocardial infarction by a mechanism of action other than coronary vasodilation. The author studied various models of experimental myocardial infarction, and selected the model described by Rona et al. (1959) because of its easy duplicability, simplicity in procedure and histopathological similarity to myocardial infarction in men. The present study was undertaken to investigate biochemical and histopathological changes induced by large multiple doses of isoproterenol in rats and to obtain information about effects of some drugs on these changes. Methods: 1. Male Wistar rats, weighing 190 to 250g, were used in this study. Cardiac necrosis enlargement were induced by dl-isoproterenol at a dose of 80mg/kg s.c. daily for two days, and examined at various stages. Time course changes in the development of myocardial necrosis were examined by biochemical and histopathological procedures. Effects of some drugs on myocardial necrosis were also investigated. 2. Biochemical determination Serum enzymes: Serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) were measured by the method of Reitman and Frankel, and creatine phosphokinase (CPK) by the Kuby's method. Serum lipids: Cholesterol and triglycerides were determined by the method of Technicon's autoanalyzer methodology N-24a and methodology N-70 respectively. Serum free fatty acids (FFA) were measured by the Novak's method (the animals unfasted). Hematocrit (Ht.): By high speed centrifugation.
The neuronal cell adhesion molecule L1CAM as a therapeutic targe in breast cancer.
Authors: J. Jassem, R. Duchnowska, W. Biernat, L. M. Evans, D. P. Fitzgerald, S. Woditschka, B. Szostakiewicz, T. Mandat, B. Jarosz, T. Trojanowski, F. Szubstarski, B. Arlukowicz-Czartoryska, R. Staszkiewicz, B. Szostak, W. Olszewski, P. S. Steeg, L. Li, G. W. Sledge, D. Palmieri, S. S. Badve
Journal: Journal of Clinical Oncology (2011)

e21138 Background: Brain metastases of breast cancer occurs in approximately one-third of metastatic triple negative and HER2+ breast cancer patients and contributes to patient morbidity and mortality. The identification and validation of molecular pathways underlying brain metastases of breast cancer may lead to the development of effective therapeutics. Methods: We have identified 23 sets of matched primary breast tumors and resected brain metastases, and determined their gene expression profiles using the DASL platform on formalin-fixed, paraffin embedded tumor sections. Multiple independent shRNAs to L1CAM or a control shRNA were transfected into a brain metastatic derivative (231-BR) of human MDA-MB-231 breast carcinoma cells. Brain metastases were quantified one month after intracardiac injection. Results: Patient characteristics: mean age at diagnosis of brain metastases: 48 years (range 29-68 years); 10 HER2+(3+)/ER- (43.5%), 1 HER2(2+)/ER- (4.4%), 2 HER2(2+)/ER+ (8.7%), 3 HER2-/ER+ (13%), 2 HER2(3+)/ER+ (8.7%) 5 triple negative (22%), median time from diagnosis to brain metastases was 2.5 years (range 0 to 11.8 years). Of 502 genes, 12 were significantly overexpressed in brain metastases as compared to matched primary tumors by >1.5 fold; each of the 12 genes was also overexpressed in resected brain metastases as compared to systemic human metastases in an online microarray database. One of these, L1CAM, a neuronal cell adhesion molecule involved in axon motility and tracking, was upregulated 1.6-fold in the brain metastases relative to the primary tumors (p= 0.037). L1CAM protein was upregulated 6.4-fold in 231-BR cells relative to MDA-MB-231. Control shRNA- and L1CAM shRNA transfected 231-BR cells produced equivalent numbers of brain micrometastases; knockdown of L1CAM inhibited the development of large (>1 mm) metastases in a mouse brain by 2-fold (p= 0.038). Conclusions: L1CAM neuronal cell adhesion protein is acquired in human brain metastases of breast cancer and functionally promotes the formation of large brain metastases, identifying it as a new therapeutic target.
Abstract 890: Effects of Lewis lung carcinoma on trabecular microstructural changes in wild-type and plasminogen activator inhibitor-1 deficient mice fed a high-fat diet
Authors: Lin Yan
Journal: Cancer Research (2015)

Abstract Bone is a major target organ of metastasis. The present study investigated the effects of Lewis lung carcinoma (LLC) on trabecular microstructural changes, using tomographic analysis, in distal femur and lumbar 4 vertebra from LLC-bearing wild-type and plasminogen activator inhibitor-1 (PAI-1) deficient mice (C57BL/6J background) fed the AIN93G diet or a high-fat diet; a group of AIN93G-fed non-tumor-bearing wild-type mice were used as controls. Compared to AIN93G-fed non-tumor-bearing wild-type mice, LLC significantly reduced bone volume fraction (BV/TV), connective density (Conn.D), trabecular number (Tb.N), trabecular thickness (Tb.Th) and bone mineral density (BMD) and significantly increased trabecular separation (Tb.Sp) in distal femurs of AIN93G-fed wild-type mice. In high-fat diet-fed mice, compared to the AIN93G-fed ones, LLC resulted in significantly greater reductions BV/TV, Conn.D, Tb.N and BMD and significantly greater increases in structure model index (SMI) and Tb.Sp. Deficiency in PAI-1, compared to wild-type mice, significantly increased BV/TV, Conn.D, Tb.N and significantly reduced SMI. In vertebra, LLC resulted in similar trabecular changes compared to the non-tumor-bearing wild-type controls, the high-fat diet reduced BV/TV and BMD and increased SMI, whereas PAI-1 deficiency did not affect trabecular microstructure in vertebrae. These results demonstrated (1) that LLC is detrimental to trabecular bone which may make it more vulnerable to malignant invasion, (2) that high-fat diet enhances LLC-induced trabecular deterioration and (3) that the improvement in trabecular microstructure by PAI-1 deficiency indicates that PAI-1 may play a role in trabecular microarchitectural deterioration during malignant progression. Citation Format: Lin Yan. Effects of Lewis lung carcinoma on trabecular microstructural changes in wild-type and plasminogen activator inhibitor-1 deficient mice fed a high-fat diet. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 890. doi:10.1158/1538-7445.AM2015-890
Unique Versus Common: Disease-Biased Immunoglobulin Gene Repertoires Along with Public Antigen Receptor Stereotypes in Marginal Zone B-Cell Lymphoproliferations
Authors: Aliki Xochelli, Vasilis Bikos, Eleftheria Polychronidou, Andreas Agathangelidis, Frederic Charlotte, Panagiotis Moschonas, Zadie Davis, Monica Colombo, Maria Roumelioti, Lesley-Ann Sutton, Patricia Groenen, Myriam Boudjoghra, Patricia Algara, Alexandra Traverse-Glehen, Ana Ferrer, Evangelia Stalika, Maria Karypidou, George Kanellis, Christina Kalpadakis, Manuella Mollejo, Gerasimos Pangalis, Panayiotis Vlamos, Rose-Marie Amini, Sarka Pospisilova, David Gonzalez, Maurilio Ponzoni, Achilles Anagnostopoulos, Veronique Giudicelli, Marie-Paule Lefranc, Blanca Espinet, Panagiotis Panagiotidis, Miguel Angel Piris, Ming Du, Richard Rosenquist, Theodora Papadaki, Chrysoula Belessi, Manlio Ferrarini, David Oscier, Dimitrios Tzovaras, Paolo Ghia, Frederic Davi, Anastasia Hadzidimitriou, Kostas Stamatopoulos
Journal: Blood (2015)
Management and treatment of soft tissue sarcoma patients by medical oncologists in multidisciplinary center
Authors: Kenji Nakano, Junichi Tomomatsu, Noriko Motoi, Tabu Gokita, Keisuke Ae, Taisuke Tanizawa, Takashi Shimoji, Seiichi Matsumoto, Shunji Takahashi
Journal: Annals of Oncology (2015)
Microfluidic and Flow Cytometric Studies Support a Role for Monocytes and Coated Platelets in the Prothrombotic State in Heparin-Induced Thrombocytopenia (HIT)
Authors: Valerie Tutwiler, Hyun Sook Ahn, Douglas B. Cines, Rodney M. Camire, Mortimer Poncz, Steven McKenzie, Lubica Rauova
Journal: Blood (2011)
Mutational Analysis of TP53 Gene in Chronic Lymphocytic Leukemia: Comparison of Different Methodological Approaches
Authors: Barbara Kantorova, Jitka Malcikova, Jana Kminkova, Veronika Navrkalova, Barbora Dvorakova, Boris Tichy, Jana Smardova, Martin Trbusek, Sim Truong, Katerina Stano-Kozubik, Nikola Tom, Karol Pal, Ludmila Sebejova, Nancy Patten, Lin Wu, Michael Doubek, Jiri Mayer, Sarka Pospisilova
Journal: Blood (2012)
Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference
Authors: Timothy H.J. Goodship, H. Terence Cook, Fadi Fakhouri, Fernando C. Fervenza, Véronique Frémeaux-Bacchi, David Kavanagh, Carla M. Nester, Marina Noris, Matthew C. Pickering, Santiago Rodríguez de Córdoba, Lubka T. Roumenina, Sanjeev Sethi, Richard J.H. Smith, Charlie E. Alpers, Gerald B. Appel, Gianluigi Ardissino, Gema Ariceta, Mustafa Arici, Arvind Bagga, Ingeborg M. Bajema, Miguel Blasco, Linda Burke, Thomas D. Cairns, Mireya Carratala, Vivette D. D'Agati, Mohamed R. Daha, An S. De Vriese, Marie-Agnès Dragon-Durey, Agnes B. Fogo, Miriam Galbusera, Daniel P. Gale, Hermann Haller, Sally Johnson, Mihály Józsi, Diana Karpman, Lynne Lanning, Moglie Le Quintrec, Christoph Licht, Chantal Loirat, Francisco Monfort, B. Paul Morgan, Laure-Hélène Noël, Michelle M. O'Shaughnessy, Marion Rabant, Eric Rondeau, Piero Ruggenenti, Neil S. Sheerin, Jenna Smith, Fabrizio Spoleti, Joshua M. Thurman, Nicole C.A.J. van de Kar, Marina Vivarelli, Peter F. Zipfel
Journal: Kidney International (2016)

In both atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G) complement plays a primary role in disease pathogenesis. Herein we report the outcome of a 2015 Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference where key issues in the management of these 2 diseases were considered by a global panel of experts. Areas addressed included renal pathology, clinical phenotype and assessment, genetic drivers of disease, acquired drivers of disease, and treatment strategies. In order to help guide clinicians who are caring for such patients, recommendations for best treatment strategies were discussed at length, providing the evidence base underpinning current treatment options. Knowledge gaps were identified and a prioritized research agenda was proposed to resolve outstanding controversial issues.
Effect of standard therapy on lymphocyte subsets and cytokines in newly diagnosed high-grade gliomas (HGG).
Authors: A. S. Balmanoukian, S. A. Grossman, C. Thoburn, F. Kos, M. Holdhoff, A. Hess
Journal: Journal of Clinical Oncology (2011)

2045 Background: Radiation (RT), temozolomide (TMZ), and glucocorticoids are each lymphotoxic and when combined to treat HGG, CD4 counts fall within 2 months of initiating therapy. This study characterizes changes in lymphocyte subsets and various cytokines before and after treatment with concurrent RT and TMZ. Methods: Blood was collected prior to therapy, 4 weeks after completing RT+TMZ, and 1-2 months thereafter from patients (pt) with newly diagnosed HGG. This was assayed for total lymphocyte count, CD4, CD8, effector T, naïve and activated T regulatory, natural killer cells, and CD19+ B cells using FLOW cytometry. Cytokine levels were measured using the Bio-Plex Human Cytokine 23-plex assay. Results: Data is available from 13 pts (10 GBM, 2 AA, and 1 AO), median age = 55 (range 32-74), Karnofsky performance status = 90 (range 70-100) and average dexamethasone dose = 6 mg/day (range 0-16). A substantial decrease in total lymphocyte count, CD4 count and B cells was noted following therapy. Minor fluctuations were noted in CD8, natural killer, and T regulatory cells. Lymphocyte values are presented below as median (+/- SD) in mm3. Preliminary cytokine analysis is available on 4 pts comparing pre-therapy to 14-18 weeks later as median (+/-SD): INF-γ from 137 (±842) to 567 (±938); IL-2 from 13 (±115) to 87 (±74); TNF from 40 (±502) to 32 (±131); and IL-4 from 2.1 (±0.7) to 3.38 (±9.3). Serum VEGF levels may decrease over time following therapy from 136 pg/nm (±110) to 98 (±27). Conclusions: Preliminary findings from this ongoing study suggest that RT+TMZ result in significant reductions in total lymphocyte, CD4, and B cells but not CD8 cells. Changes in plasma VEGF levels are of interest while other cytokine changes are less pronounced. Further data regarding these iatrogenic changes in the immune system are critical to improving therapies with novel agents and vaccines. Total lymphocyte CD4 CD8 Naive T regs Activated T regs Effector T Natural killer CD19+ B Pre-therapy 1170 (±375) 531 (±251) 426 (±158) 3.4 (±6.8) 5.3 (±9.3) 55 (±14) 410 (±273) 146 (±228) 10 weeks 900 (±424) 282 (±157) 461 (±302) 3.85 (±8.1) 9.4 (±5.8) 47 (±22) 434 (±361) 52 (±47) 14-18 weeks 747 (±386) 225 (±203) 462 (±169) 2.1 (±4.2) 5.5 (±11.7) 27 (±23) 368 (±373) 38 (±33)
Oral Administration of Low-Dose Decitabine and Tetrahydrouridine In Combination Increases Fetal Hemoglobin to Therapeutic Levels In the Absence of Cytotoxicity and Reduces Inter-Individual Drug Bioavailability In Baboons
Authors: Donald Lavelle, Kestutis Vaitkus, Maria Armila Ruiz, Cassandra List, Tatiana Kouznetsova, Joseph DeSimone, Yogen Saunthararajah
Journal: Blood (2011)
Evolution of DNA Methylation across Insects
Authors: Adam J. Bewick, Kevin J. Vogel, Allen J. Moore, Robert J. Schmitz
Journal: Molecular Biology and Evolution (2016)

DNA methylation contributes to gene and transcriptional regulation in eukaryotes, and therefore has been hypothesized to facilitate the evolution of plastic traits such as sociality in insects. However, DNA methylation is sparsely studied in insects. Therefore, we documented patterns of DNA methylation across a wide diversity of insects. We predicted that underlying enzymatic machinery is concordant with patterns of DNA methylation. Finally, given the suggestion that DNA methylation facilitated social evolution in Hymenoptera, we tested the hypothesis that the DNA methylation system will be associated with presence/absence of sociality among other insect orders. We found DNA methylation to be widespread, detected in all orders examined except Diptera (flies). Whole genome bisulfite sequencing showed that orders differed in levels of DNA methylation. Hymenopteran (ants, bees, wasps and sawflies) had some of the lowest levels, including several potential losses. Blattodea (cockroaches and termites) show all possible patterns, including a potential loss of DNA methylation in a eusocial species whereas solitary species had the highest levels. Species with DNA methylation do not always possess the typical enzymatic machinery. We identified a gene duplication event in the maintenance DNA methyltransferase 1 (DNMT1) that is shared by some Hymenoptera, and paralogs have experienced divergent, nonneutral evolution. This diversity and nonneutral evolution of underlying machinery suggests alternative DNA methylation pathways may exist. Phylogenetically corrected comparisons revealed no evidence that supports evolutionary association between sociality and DNA methylation. Future functional studies will be required to advance our understanding of DNA methylation in insects.