tbuckley/cabot-search huggingface dataset:
A liver‐specific gene expression panel predicts the differentiation status of in vitro hepatocyte models
Authors: Dae‐Soo Kim, Jea‐Woon Ryu, Mi‐Young Son, Jung‐Hwa Oh, Kyung‐Sook Chung, Sugi Lee, Jeong‐Ju Lee, Jun‐Ho Ahn, Ju‐Sik Min, Jiwon Ahn, Hyun Mi Kang, Janghwan Kim, Cho‐Rok Jung, Nam‐Soon Kim, Hyun‐Soo Cho
Journal: Hepatology (2017)

Alternative cell sources, such as three-dimensional organoids and induced pluripotent stem cell-derived cells, might provide a potentially effective approach for both drug development applications and clinical transplantation. For example, the development of cell sources for liver cell-based therapy has been increasingly needed, and liver transplantation is performed for the treatment for patients with severe end-stage liver disease. Differentiated liver cells and three-dimensional organoids are expected to provide new cell sources for tissue models and revolutionary clinical therapies. However, conventional experimental methods confirming the expression levels of liver-specific lineage markers cannot provide complete information regarding the differentiation status or degree of similarity between liver and differentiated cell sources. Therefore, in this study, to overcome several issues associated with the assessment of differentiated liver cells and organoids, we developed a liver-specific gene expression panel (LiGEP) algorithm that presents the degree of liver similarity as a "percentage." We demonstrated that the percentage calculated using the LiGEP algorithm was correlated with the developmental stages of in vivo liver tissues in mice, suggesting that LiGEP can correctly predict developmental stages. Moreover, three-dimensional cultured HepaRG cells and human pluripotent stem cell-derived hepatocyte-like cells showed liver similarity scores of 59.14% and 32%, respectively, although general liver-specific markers were detected.Our study describes a quantitative and predictive model for differentiated samples, particularly liver-specific cells or organoids; and this model can be further expanded to various tissue-specific organoids; our LiGEP can provide useful information and insights regarding the differentiation status of in vitro liver models. (Hepatology 2017;66:1662-1674).
Improved tumor imaging and therapy via i.v. IgG–mediated time-sequential modulation of neonatal Fc receptor
Authors: Jaspreet Singh Jaggi, Jorge A. Carrasquillo, Surya V. Seshan, Pat Zanzonico, Erik Henke, Andrew Nagel, Jazmin Schwartz, Brad Beattie, Barry J. Kappel, Debjit Chattopadhyay, Jing Xiao, George Sgouros, Steven M. Larson, David A. Scheinberg
Journal: Journal of Clinical Investigation (2007)
Sixty seconds on . . . sex with robots
Authors: Ingrid Torjesen
Journal: BMJ (2017)

Actually, this is an important medical issue. Robots specifically designed to satisfy the owner’s sexual desires are available to buy now. They don’t look that unlike “human” robots seen in futuristic films such as Westworld . Some of them can even speak, and designers are working on including artificial intelligence to make them better companions.

Four companies are now marketing adult sex robots for between $5000 and $15 000 …
Abstract #5456: Correlation between inhibition of the activity of poly(ADP-ribose) polymerase (PARP) in human peripheral blood mononuclear cells (PBMCs) and tumor biopsies following treatment with ABT-888, an inhibitor of PARP
Authors: Shivaani Kummar, Larry Rubinstein, Robert Kinders, Jiuping Ji, Ralph Parchment, Martin Gutierrez, Anthony Murgo, Alice Chen, Sonny Khin, Yiping Zhang, Dwight Simmons, Mary Ann Yancey, Deborah Allen, Yvonne Horneffer, Lamin Juwara, Richard Chang, Gary Gordon, Joseph Tomaszewski, James Doroshow
Journal: Cancer Research (2009)

Introduction:  The ability to use PBMCs as a surrogate for drug effect in tumor biopsies has obvious advantages. To assess whether there was a correlation between inhibition of PARP activity in PBMCs and tumor biopsies following administration of ABT-888, an inhibitor of PARP, we pooled data from 9 patients with advanced solid tumors enrolled on two different trials evaluating ABT-888.  Methods:  Paired PBMC and tumor biopsy samples were obtained before and after the first dose of ABT-888 in the phase 0 single-agent trial of ABT-888 (6 patients), and the phase 1 trial of ABT-888 in combination with topotecan (3 patients). The level of PARP activity was determined by measuring PAR by a validated ELISA.  Results: $$table_{7394D07F-51A0-4453-9484-709493CC6BEB}$$    * 3-6 hours post drug administration  \#8224; 3-6 hours post administration of the combination The overall correlation coefficient for the two measures of percent inhibition in PBMCs versus tumor is 0.90, suggesting that 81% of the variation from the mean for percent inhibition in tumor is predicted by percent inhibition in PBMCs. The 95% lower confidence bound on the correlation coefficient is 0.67. This indicates that there is 95% confidence that at least 45% of the variation from the mean for percent inhibition in tumor is predicted by percent inhibition in PBMCs.  Conclusions:  If these preliminary results are confirmed in a larger cohort of patients, the use of ABT-888 and possibly other PARP inhibitors in future trials might be guided by PAR measurements in PBMCs instead of tumor biopsies. Use of PBMCs as a tumor surrogate would allow repetitive, non-invasive monitoring of drug effect. The ability to relate PK exposure to PD response could provide important data for designing future clinical trials with these agents, and provide a model for other targeted agents. Funded in part by NCI Contract No. HHSN261200800001E.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5456.
Pharmacogenetic Markers of Treatment Response of Imatinib Mesylate in Chronic Myeloid Leukemia Brazilian Patients
Authors: Natália M Vieira, Renata Leite, Fabíola Reginato, Marília Zandoná, Tito Vanelli Costa, Laura Fogliatto, Rafael Linden, Marina Venzon Antunes, Arnaud Capron, Pierre Wallemacq, Sandrine Wagner, Vanessa Mattevi, Marcelo Capra
Journal: Blood (2016)
Endothelial Cell-Selective Adhesion Molecule (ESAM) Is Required for the Ontogeny of Definitive Hematopoietic System in Mice
Authors: Tomoaki Ueda, Takafumi Yokota, Yasuhiro Shingai, Yukiko Doi, Tomohiko Ishibashi, Takao Sudo, Yasuhiro Nagate, Akira Tanimura, Masahiro Tokunaga, Jiro Fujita, Michiko Ichii, Sachiko Ezoe, Hirohiko Shibayama, Kenji Oritani, Yuzuru Kanakura
Journal: Blood (2016)
A monocyte‐TNF‐endothelial activation axis in sickle transgenic mice: Therapeutic benefit from TNF blockade
Authors: Anna Solovey, Arif Somani, John D. Belcher, Liming Milbauer, Lucile Vincent, Rafal Pawlinski, Karl A. Nath, Robert J. Kelm, Nigel Mackman, M. Gerard O'Sullivan, Kalpna Gupta, Gregory M. Vercellotti, Robert P. Hebbel
Journal: American Journal of Hematology (2017)

Abstract Elaboration of tumor necrosis factor (TNF) is a very early event in development of ischemia/reperfusion injury pathophysiology. Therefore, TNF may be a prominent mediator of endothelial cell and vascular wall dysfunction in sickle cell anemia, a hypothesis we addressed using NY1DD, S+S Antilles , and SS‐BERK sickle transgenic mice. Transfusion experiments revealed participation of abnormally activated blood monocytes exerting an endothelial activating effect, dependent upon Egr‐1 in both vessel wall and blood cells, and upon NFκB(p50) in a blood cell only. Involvement of TNF was identified by beneficial impact from TNF blockers, etanercept and infliximab, with less benefit from an IL‐1 blocker, anakinra. In therapeutic studies, etanercept ameliorated multiple disturbances of the murine sickle condition: monocyte activation, blood biomarkers of inflammation, low platelet count and Hb, vascular stasis triggered by hypoxia/reoxygenation (but not if triggered by hemin infusion), tissue production of neuro‐inflammatory mediators, endothelial activation (monitored by tissue factor and VCAM‐1 expression), histopathologic liver injury, and three surrogate markers of pulmonary hypertension (perivascular inflammatory aggregates, arteriolar muscularization, and right ventricular mean systolic pressure). In aggregate, these studies identify a prominent—and possibly dominant—role for an abnormal monocyte‐TNF‐endothelial activation axis in the sickle context. Its presence, plus the many benefits of etanercept observed here, argue that pilot testing of TNF blockade should be considered for human sickle cell anemia, a challenging but achievable translational research goal.
Whole genome sequencing (WGS) to reveal the distinct genomic landscape of pulmonary lymphoepithelioma-like carcinoma (LELC).
Authors: Shaodong Hong, Kui Wu, Dongbing Liu, Wenfeng Fang, Li Zhang
Journal: Journal of Clinical Oncology (2016)

1530 Background: Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare and distinct type of primary lung cancer which is characterized by Epstein-Barr virus (EBV) infection. The genomic alterations of pulmonary LELC remains unknown and well-established treatment strategies are not available. We described the first whole genome sequencing (WGS) study of this virus-associated lung cancer. Methods: Forty-one fresh LELC tumors and adjacent normal tissues underwent WGS on Complete Genomics Platform with ~100× of depth and over 95% of coverage. Somatic mutations, copy number alterations, structural rearrangements were identified by in-depth bioinformatic analyses. Results: The demographics of 41 patients enrolled in the study: median age 53 years (range: 32-69), female 20 (48.8%) and history of tobacco smoking 12 (29.3%). A total of 1674 mutations including 1172 non-silent mutations, 483 silent mutations and 19 indels were identified. The mutation rate of pulmonary LELC is remarkably low compared with other primary lung cancers (1.24 vs. 8-11 mutation/Mb). Unsupervised clustering of mutational signatures revealed that pulmonary LELC resembles nasopharyngeal carcinoma (NPC) and NK/T lymphoma rather than primary lung cancers or EBV-related gastric cancer. We found TP53, DDX11 and CGREF1 to be the most frequently mutated genes with mutations in 22.0%, 12.2% and 10.0% of individuals, respectively. Two genetic signatures of pulmonary LELC including signature 1A and signature 2 were identified. Conclusions: Pulmonary LELC is distinct from other primary lung cancers and is genetically similar to NPC and NK/T lymphoma. Our results illustrate a comprehensive genomic landscape of pulmonary LELC and provide a road map to facilitate genome-guided personalized treatment. More indepth biological and clinical studies are required to better understand pulmonary LELC.
Alcohol consumption as a risk factor for tuberculosis: meta-analyses and burden of disease
Authors: Sameer Imtiaz, Kevin D. Shield, Michael Roerecke, Andriy V. Samokhvalov, Knut Lönnroth, Jürgen Rehm
Journal: European Respiratory Journal (2017)

Meta-analyses of alcohol use, alcohol dosage and alcohol-related problems as risk factors for tuberculosis incidence were undertaken. The global alcohol-attributable tuberculosis burden of disease was also re-estimated. Systematic searches were conducted, reference lists were reviewed and expert consultations were held to identify studies. Cohort and case-control studies were included if there were no temporal violations of exposure and outcome. Risk relations (RRs) were pooled by using categorical and dose-response meta-analyses. The alcohol-attributable tuberculosis burden of disease was estimated by using alcohol-attributable fractions. 36 of 1108 studies were included. RRs for alcohol use and alcohol-related problems were 1.35 (95% CI 1.09–1.68; I 2 : 83%) and 3.33 (95% CI 2.14–5.19; 87%), respectively. Concerning alcohol dosage, tuberculosis risk rose as ethanol intake increased, with evidence of a threshold effect. Alcohol consumption caused 22.02 incident cases (95% CI 19.70–40.77) and 2.35 deaths (95% CI 2.05–4.79) per 100 000 people from tuberculosis in 2014. Alcohol-attributable tuberculosis incidence increased between 2000 and 2014 in most high tuberculosis burden countries, whereas mortality decreased. Alcohol consumption was associated with an increased risk of tuberculosis in all meta-analyses. It was consequently a major contributor to the tuberculosis burden of disease.
Inhibition of MDR1 Overcomes Brentuximab Vedotin Resistance in Hodgkin Lymphoma Cell Line Model and Is Synergistic with Brentuximab Vedotin in Mouse Xenograft Model
Authors: Robert W Chen, Jessie Hou, Indu Nair, Jun Wu, Tim Synold, Larry W. Kwak, Steven T. Rosen, Stephen J. Forman, Susan Kane, Edward Newman
Journal: Blood (2016)
Abstract 085: Anti-Inflammatory Treatment Reverses The Age-Related Increase In Catecholamine Biosynthetic Enzyme Tyrosine Hydroxylase And NYP In The Adrenal Medulla
Authors: Nihal Tumer, Thomas C Foster, Brandi Ormerod, Philip J Scarpace
Journal: Circulation Research (2013)

Aging is associated with both elevated blood pressure and decreased baroreceptor sensitivity. These have been attributed to increased sympathetic nerve activity with age. One marker of sympathoactivation is protein levels of tyrosine hydoxylase (TH) in the adrenal medulla (AM), and TH levels markedly increase with age. There is also an increase in inflammation with age. To test the hypothesis that increased inflammation with age contributes to the elevated TH levels in the AM, we examined treatment with the anti-inflammatory agents, indomethacin (10 mg/kg, BID) or rosiglitazone (1 mg/kg, BID) on TH synthesis in F344 rats of three ages, 5, 12, 18 months. In addition, NPY, a peptide that is synthesized and co-released with catecholamines in the AM, as well as angiotensin II receptor subtypes, AT1 and AT2 protein levels were assessed in the AM following the anti-inflammatory treatments. Indomethacin and rosiglitazone were administered orally as part of a frozen strawberry treat for 16 days. Although there were no changes in TH or NPY levels between the 5 mo and 12 mo old control animals, TH and NPY were elevated by 27% and 45% (P&lt;0.05), respectively in the 18 compared with 5 mo rats. These age-related increases were completely reversed by treatment with indomethacin or rosiglitazone (P&lt;0.05). There was no effect of either treatment on AT1 or AT2 receptor protein, although AT1 receptor protein levels diminished slightly with age. These data indicate that anti-inflammatory treatment reverses the elevated TH and NPY in AM with age. Increased inflammation with age indirectly through elevated catecholamine synthesis may be contributing to the increased prevalence of hypertension with age.
Rituximab biosimilar and reference rituximab in patients with previously untreated advanced follicular lymphoma (ASSIST-FL): primary results from a confirmatory phase 3, double-blind, randomised, controlled study
Authors: Wojciech Jurczak, Ilídia Moreira, Govind Babu Kanakasetty, Eduardo Munhoz, Maria Asunción Echeveste, Pratyush Giri, Nelson Castro, Juliana Pereira, Luiza Akria, Sergey Alexeev, Eugeniy Osmanov, Peijuan Zhu, Siyka Alexandrova, Angela Zubel, Olof Harlin, Jutta Amersdorffer
Journal: The Lancet Haematology (2017)
Involvement of nuclear factor kappa B in the upregulation of cyclooxygenase-2 expression by HPV 16 E5 through EGFR and its signaling pathways
Authors: Su-Hyeong Kim, Jung-Min Oh, Yung-Jue Bang, Yung-Sung Juhnn, Yong-Sang Song
Journal: Cancer Research (2007)

4260   Overexpression of cyclooxygenase-2 (COX-2) has been found to be associated with the metastasis of cervical cancer. The mechanisms regulating COX-2 expression in cervical cancer have never been studied. COX-2 expression in human tumors can be induced by growth factors, inflammatory cytokines and other factors. HPV 16 E5 is one of three viral oncogenes, which activates growth factor receptors. So we tested the presence of HPV 16 E5-induced COX-2 expression and its regulatory mechanism.Transduction of HPV 16 E5 oncogene resulted in the upregulation of COX-2 expression. Upregulation of COX-2 expression by HPV 16 E5 seemed to be associated with the amount of HPV 16 E5 gene transfected and regardless of cell type. Its upregulation was associated with the increased transcriptional activity, but not the mRNA stability of COX-2. Transient transfection of deletional and mutant constructs of COX-2 promoter demonstrated that the promoter region, -327 to -220, and NF-kappaB binding site were very important in the upregulation of COX-2 by HPV 16 E5. Western blotting analysis also showed the nuclear movement of p50/p65 heterodimer following the degradation of IkappaB-alpha and a luciferase reporter gene assay of repeated NF-kappaB binding sites confirmed NF-kappaB activation by E5. Upregulation of COX-2 expression along with the promoter activity of COX-2 was attenuated by TPCK blockers, such as the serine protease inhibitors N-alpha-tosyl-L-phenylalanine chloromethyl ketone (TPCK) and IKK inhibitor Bay 11-7082. Phosphorylation and inhibitor assays showed that this upregulation was significantly inhibited by a selective EGFR tyrosine kinase inhibitor (AG1478) and pharmacological inhibitors of the MEK-ERK1/2 and PI3K/Akt pathways. Furthermore, we found that COX-2 promoter activity could be modulated by pharmacological inhibitors of the EGFR, MEK-ERK1/2 and PI3K/Akt pathways in E5-expressing cells. Taken together, these novel results suggest that COX-2 expression in cervical carcinogenesis may depend on the NF-kappaB transcriptional activity, modulated by EGFR and its signaling pathways at least in part.
Operative versus non-operative management of adhesive small bowel obstruction: A systematic review and meta-analysis
Authors: Shahab Hajibandeh, Shahin Hajibandeh, Nilanjan Panda, Rao Muhammad Asaf Khan, Samik Kumar Bandyopadhyay, Sanjay Dalmia, Sohail Malik, Zahirul Huq, Moustafa Mansour
Journal: International Journal of Surgery (2017)
Overall survival and updated progression-free survival results from a randomized phase 2 trial comparing the combination of olaparib and cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer.
Authors: Joyce F. Liu, William Thomas Barry, Michael J. Birrer, Jung-min Lee, Ronald J. Buckanovich, Gini F. Fleming, Bj Rimel, Mary K. Buss, Sreenivasa R. Nattam, Jean Hurteau, Weixiu Luo, Sarah Farooq, Christin Whalen, Elise C. Kohn, S. Percy Ivy, Ursula A. Matulonis
Journal: Journal of Clinical Oncology (2017)

5535 Background: We previously reported that the combination of cediranib (ced) and olaparib (olap) improved progression-free survival (PFS) and overall response rates (ORR) in women with recurrent platinum-sensitive (plat-sens) high-grade serous (HGS) or BRCA-related ovarian cancer (OvCa) (NCT 01116648). We conducted an updated PFS and overall survival (OS) analysis. Methods: Patients (pts) across 9 centers were randomized 1:1 in this Ph 2 open label study to Olap (olap 400 mg capsules BID) or Ced/Olap (olap 200 mg capsules BID; ced 30 mg daily), stratified by BRCA status and prior anti-angiogenic therapy. Eligibility included pts with recurrent plat-sens HGS or BRCA-related OvCa. Pts had measurable disease by RECIST 1.1, PS 0 or 1, and the ability to take POs. No prior anti-angiogenics in the recurrent setting or prior PARP inhibitor was allowed. PFS was defined as time from randomization to radiographic progression or death. OS was defined as time from randomization to death. Results: Pts were enrolled from Oct 2011 to Jun 2013: 46 to Olap, 44 to Ced/Olap. 48 pts were known BRCA carriers (25 Olap; 23 Ced/Olap). As of Dec 21, 2016, 67 pts had a PFS event, and 52 pts had an OS event. Updated median PFS was 8.2 mos for Olap and 16.5 mos for Ced/Olap (HR 0.50, 95% CI 0.30-0.83, p=0.007). Median OS was 33.3 mos for Olap and 44.2 mos for Ced/Olap (HR 0.64, 95% CI 0.36-1.11, p=0.11). Within known germline BRCA mut carriers, updated PFS was 16.5 vs 16.4 mos (HR 0.75, p=0.42), and OS was 40.1 vs 44.2 mos (HR 0.79, p=0.55) for Olap and Ced/Olap, respectively. In pts without known germline BRCA mut, updated PFS was 5.7 vs 23.7 mos (HR 0.32, p=0.002), and OS was 23.0 vs 37.8 mos (HR 0.48, p=0.074). Conclusions: Updated PFS results consistently demonstrated that Ced/Olap significantly extended PFS compared to Olap in the overall population of women with plat-sens OvCa. In this Phase 2 study not powered to detect OS diferences, there was a trend towards OS improvement with Ced/Olap, particularly in pts without a known germline BRCA mutation. Results from ongoing studies of this oral combination in OvCa are of clinical interest. Clinical trial information: NCT 01116648.
TCR-CXCR4 signaling stabilizes cytokine mRNA transcripts via a PREX1-Rac1 pathway: implications for CTCL
Authors: Kimberly N. Kremer, Brittney A. Dinkel, Rosalie M. Sterner, Douglas G. Osborne, Dragan Jevremovic, Karen E. Hedin
Journal: Blood (2017)
Measles Outbreak — Minnesota April–May 2017
Authors: Victoria Hall, Emily Banerjee, Cynthia Kenyon, Anna Strain, Jayne Griffith, Kathryn Como-Sabetti, Jennifer Heath, Lynn Bahta, Karen Martin, Melissa McMahon, Dave Johnson, Margaret Roddy, Denise Dunn, Kristen Ehresmann
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

On April 10, 2017, the Minnesota Department of Health (MDH) was notified about a suspected measles case. The patient was a hospitalized child aged 25 months who was evaluated for fever and rash, with onset on April 8. The child had no history of receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles. On April 11, MDH received a report of a second hospitalized, unvaccinated child, aged 34 months, with an acute febrile rash illness with onset on April 10. The second patient's sibling, aged 19 months, who had also not received MMR vaccine, had similar symptoms, with rash onset on March 30. Real-time reverse transcription-polymerase chain reaction (rRT-PCR) testing of nasopharyngeal swab or throat specimens performed at MDH confirmed measles in the first two patients on April 11, and in the third patient on April 13; subsequent genotyping identified genotype B3 virus in all three patients, who attended the same child care center. MDH instituted outbreak investigation and response activities in collaboration with local health departments, health care facilities, child care facilities, and schools in affected settings. Because the outbreak occurred in a community with low MMR vaccination coverage, measles spread rapidly, resulting in thousands of exposures in child care centers, schools, and health care facilities. By May 31, 2017, a total of 65 confirmed measles cases had been reported to MDH (Figure 1); transmission is ongoing.
Steroid Dependent Recalcitrant Well's Syndrome in a Patient with Chronic Lymphocytic Leukemia (CLL) Responding to Hydroxychloroquine (HCQS)
Authors: Prabhsimranjot Singh, Makardhwaj S Shrivastava, Audrik Perez, Kenneth Grossman, Daniel Benasher, Alan Astrow
Journal: Blood (2016)
A FOXO1-induced oncogenic network defines the AML1-ETO preleukemic program
Authors: Shan Lin, Anetta Ptasinska, Xiaoting Chen, Mahesh Shrestha, Salam A. Assi, Paulynn S. Chin, Maria R. Imperato, B. J. Aronow, Jingsong Zhang, Matthew T. Weirauch, Constanze Bonifer, James C. Mulloy
Journal: Blood (2017)
Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study
Authors: Jakko van Ingen, Thomas A Kohl, Katharina Kranzer, Barbara Hasse, Peter M Keller, Anna Katarzyna Szafrańska, Doris Hillemann, Meera Chand, Peter Werner Schreiber, Rami Sommerstein, Christoph Berger, Michele Genoni, Christian Rüegg, Nicolas Troillet, Andreas F Widmer, Sören L Becker, Mathias Herrmann, Tim Eckmanns, Sebastian Haller, Christiane Höller, Sylvia B Debast, Maurice J Wolfhagen, Joost Hopman, Jan Kluytmans, Merel Langelaar, Daan W Notermans, Jaap ten Oever, Peter van den Barselaar, Alexander B A Vonk, Margreet C Vos, Nada Ahmed, Timothy Brown, Derrick Crook, Theresa Lamagni, Nick Phin, E Grace Smith, Maria Zambon, Annerose Serr, Tim Götting, Winfried Ebner, Alexander Thürmer, Christian Utpatel, Cathrin Spröer, Boyke Bunk, Ulrich Nübel, Guido V Bloemberg, Erik C Böttger, Stefan Niemann, Dirk Wagner, Hugo Sax
Journal: The Lancet Infectious Diseases (2017)