tbuckley/cabot-search huggingface dataset:
Cross-specificity of protective human antibodies against Klebsiella pneumoniae LPS O-antigen
Authors: Tim Rollenske, Valeria Szijarto, Jolanta Lukasiewicz, Luis M. Guachalla, Katarina Stojkovic, Katharina Hartl, Lukas Stulik, Simone Kocher, Felix Lasitschka, Mohammed Al-Saeedi, Jutta Schröder-Braunstein, Moritz von Frankenberg, Gereon Gaebelein, Peter Hoffmann, Sabrina Klein, Klaus Heeg, Eszter Nagy, Gabor Nagy, Hedda Wardemann
Journal: Nature Immunology (2018)
Neutrophil to lymphocyte ratio and outcome in stage III non-small cell lung cancer treated with definitive chemoradiation therapy.
Authors: Hemant S. Murthy, Paul R. Walker
Journal: Journal of Clinical Oncology (2014)

e18512 Background: Neutrophil to lymphocyte ratio (NLR) has been shown to have prognostic value in various types of malignancies. Pretreatment NLR in non small cell lung cancer (NSCLC) has been studied for prognostic value prior to surgical resection (Tomita et al Anticancer Res 2011) as well as prior to initiating platinum based chemotherapy (Yao et al Cancer Immunol Immunother 2013). NLR was assessed as a prognostic indicator for outcome in inoperable stage III non-small cell lung cancer (NSCLC) treated with definitive chemoradiation therapy (CRT). Methods: Retrospective chart analysis was performed on patients with unresectable stage III NSCLC who were treated as part of a phase II protocol (Zhang et al Lung Cancer 2014) with tiw paclitaxel 15 mg/m2 IV followed by timed thoracic radiotherapy (TTR) 6 hours later on Monday/Wednesday/Friday and TTR only on Tuesday/Thursday mornings (total 55Gy). Full dose adjuvant chemotherapy consisted of intravenous carboplatin (AUC 5) on day 1, gemcitabine 1000mg/m2 on days 1 and 8, every 21 days for 4 cycles. NLR was measured at pretreatment and at 3 and 6 months post-treatment. Results: The NLR at these points was assessed in 27 patients. 24 patients had a pre-treatment NLR less than 10. At 3 months post treatment 12/19 (63%) patients had NLR < 10 and at 6 months 13/18 (72.2%) had NLR <10. 10 patients had NLR < 10 at pretreatment, 3 months and 6 months post-therapy. Of these 10, 7 were alive at 1 year post-treatment (70%). Of the 12 patients on study alive at the 1 year mark, 7 (58.3%) had NLR < 10 at pretreatment, 3 month and 6 month post-therapy. Conclusions: Maintaining a neutrophil to lymphocyte ratio lower than 10 throughout CRT treatment and early followup in unresectable stage III NSCLC had favorable prognostic value.
A Strategy for Discovery of Endocrine Interactions with Application to Whole-Body Metabolism
Authors: Marcus M. Seldin, Simon Koplev, Prashant Rajbhandari, Laurent Vergnes, Gregory M. Rosenberg, Yonghong Meng, Calvin Pan, Thuy M.N. Phuong, Raffi Gharakhanian, Nam Che, Selina Mäkinen, Diana M. Shih, Mete Civelek, Brian W. Parks, Eric D. Kim, Frode Norheim, Karthickeyan Chella Krishnan, Yehudit Hasin-Brumshtein, Margarete Mehrabian, Markku Laakso, Christian A. Drevon, Heikki A. Koistinen, Peter Tontonoz, Karen Reue, Rita M. Cantor, Johan L.M. Björkegren, Aldons J. Lusis
Journal: Cell Metabolism (2018)
Integrative Kinome Profiling Identifies mTORC1/2 Inhibition as Treatment Strategy in Ovarian Clear Cell Carcinoma
Authors: Joseph J. Caumanns, Katrien Berns, G. Bea A. Wisman, Rudolf S.N. Fehrmann, Tushar Tomar, Harry Klip, Gert J. Meersma, E. Marielle Hijmans, Annemiek M.C. Gennissen, Evelien W. Duiker, Desiree Weening, Hiroaki Itamochi, Roelof J.C. Kluin, Anna K.L. Reyners, Michael J. Birrer, Helga B. Salvesen, Ignace Vergote, Els van Nieuwenhuysen, James Brenton, E. Ioana Braicu, Jolanta Kupryjanczyk, Beata Spiewankiewicz, Lorenza Mittempergher, René Bernards, Ate G.J. van der Zee, Steven de Jong
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Advanced-stage ovarian clear cell carcinoma (OCCC) is unresponsive to conventional platinum-based chemotherapy. Frequent alterations in OCCC include deleterious mutations in the tumor suppressor ARID1A and activating mutations in the PI3K subunit PIK3CA. In this study, we aimed to identify currently unknown mutated kinases in patients with OCCC and test druggability of downstream affected pathways in OCCC models. Experimental Design: In a large set of patients with OCCC (n = 124), the human kinome (518 kinases) and additional cancer-related genes were sequenced, and copy-number alterations were determined. Genetically characterized OCCC cell lines (n = 17) and OCCC patient–derived xenografts (n = 3) were used for drug testing of ERBB tyrosine kinase inhibitors erlotinib and lapatinib, the PARP inhibitor olaparib, and the mTORC1/2 inhibitor AZD8055. Results: We identified several putative driver mutations in kinases at low frequency that were not previously annotated in OCCC. Combining mutations and copy-number alterations, 91% of all tumors are affected in the PI3K/AKT/mTOR pathway, the MAPK pathway, or the ERBB family of receptor tyrosine kinases, and 82% in the DNA repair pathway. Strong p-S6 staining in patients with OCCC suggests high mTORC1/2 activity. We consistently found that the majority of OCCC cell lines are especially sensitive to mTORC1/2 inhibition by AZD8055 and not toward drugs targeting ERBB family of receptor tyrosine kinases or DNA repair signaling. We subsequently demonstrated the efficacy of mTORC1/2 inhibition in all our unique OCCC patient–derived xenograft models. Conclusions: These results propose mTORC1/2 inhibition as an effective treatment strategy in OCCC. Clin Cancer Res; 24(16); 3928–40. ©2018 AACR.
Specialized fibroblast differentiated states underlie scar formation in the infarcted mouse heart
Authors: Xing Fu, Hadi Khalil, Onur Kanisicak, Justin G. Boyer, Ronald J. Vagnozzi, Bryan D. Maliken, Michelle A. Sargent, Vikram Prasad, Iñigo Valiente-Alandi, Burns C. Blaxall, Jeffery D. Molkentin
Journal: Journal of Clinical Investigation (2018)

Fibroblasts are a dynamic cell type that achieve selective differentiated states to mediate acute wound healing and long-term tissue remodeling with scarring. With myocardial infarction injury, cardiomyocytes are replaced by secreted extracellular matrix proteins produced by proliferating and differentiating fibroblasts. Here, we employed 3 different mouse lineage-tracing models and stage-specific gene profiling to phenotypically analyze and classify resident cardiac fibroblast dynamics during myocardial infarction injury and stable scar formation. Fibroblasts were activated and highly proliferative, reaching a maximum rate within 2 to 4 days after infarction injury, at which point they expanded 3.5-fold and were maintained long term. By 3 to 7 days, these cells differentiated into myofibroblasts that secreted abundant extracellular matrix proteins and expressed smooth muscle α-actin to structurally support the necrotic area. By 7 to 10 days, myofibroblasts lost proliferative ability and smooth muscle α-actin expression as the collagen-containing extracellular matrix and scar fully matured. However, these same lineage-traced initial fibroblasts persisted within the scar, achieving a new molecular and stable differentiated state referred to as a matrifibrocyte, which was also observed in the scars of human hearts. These cells express common and unique extracellular matrix and tendon genes that are more specialized to support the mature scar.
Effectiveness of “early” TIPS implantation versus “late” TIPS versus standard endoscopic treatment for acute variceal bleeding in patients with liver cirrhosis
Authors: T. Bucsics, M. Schoder, M. Mandorfer, P. Schwabl, F. Riedl, D. Bauer, M. Trauner, M. Peck-Radosavljevic, J. Karner, F. Karnel, T. Reiberger
Journal: Journal of Hepatology (2018)
Assembly of PEG Microgels into Porous Cell‐Instructive 3D Scaffolds via Thiol‐Ene Click Chemistry
Authors: Shangjing Xin, Omar M. Wyman, Daniel L. Alge
Journal: Advanced Healthcare Materials (2018)

The assembly of microgel building blocks into 3D scaffolds is an emerging strategy for tissue engineering. A key advantage is that the inherent microporosity of these scaffolds provides cells with a more permissive environment than conventional nanoporous hydrogels. Here, norbornene-bearing poly(ethylene glycol) (PEG) based microgels are assembled into 3D cell-instructive scaffolds using a PEG-dithiol linker and thiol-ene click photopolymerization. The bulk modulus of these materials depends primarily on the crosslink density of the microgel building blocks. However, the linker and initiator concentrations used during assembly have significant effects on cell spreading and proliferation when human mesenchymal stem cells (hMSCs) are incorporated in the scaffolds. The cell response is also affected by the properties of the modular microgel building blocks, as hMSCs growing in scaffolds assembled from stiff but not soft microgels activate Yes-associated protein signaling. These results indicate that PEG microgel scaffolds assembled via thiol-ene click chemistry can be engineered to provide a cell-instructive 3D milieu, making them a promising 3D platform for tissue engineering.
Clinical presentation and outcome of Wilson’s disease patients in a monocentric cohort of liver reference center
Authors: R. Sobesky, M. Darce, H. Agostini, I. Fernandez, A. Usardi, R. Adam, D. Cherqui, E. Gonzales, E. Jacquemin, D. Samuel, A. Poujois, F. Woimant, J.-C. Duclos-Vallée
Journal: Journal of Hepatology (2018)
TCTAP A-096 Relation Between Fractional Flow Reserve and Cardiac Events in Coronary Artery Disease
Authors: Wei-Ting Wang, Shao-Sung Huang, Shih-Hsien Sung, Cheng-Hsueh Wu, Po-Hsun Huang, Hsin-Bang Leu, Tse-Min Lu, Tao-Cheng Wu, Min-Ji Charng, Shing-Jong Lin
Journal: Journal of the American College of Cardiology (2018)
P538Sensitive detection of platelet-derived and tissue factor positive extracellular vesicles in plasma using solid-phase proximity ligation assay
Authors: A Thulin, J Yan, M Aberg, C Christersson, M Kamali-Moghaddam, A Siegbahn
Journal: Cardiovascular Research (2018)

Sensitive detection of platelet-derived and tissue factor positive extracellular vesicles in plasma using solid-phase proximity ligation assay
Disease progression is affected by pattern of serum alanine aminotransferase dynamics in a cohort of patients with hepatitis B e antigen-negative chronic infection: 4 years follow-up of a prospective longitudinal study (ALBATROS study)
Authors: V. Knop, J. Vermehren, Jörg Petersen, P. Buggisch, H. Wedemeyer, M. Cornberg, S. Mauss, M. Sprinzl, T. Berg, F. van Boemmel, H. Klinker, D. Hüppe, J.-P. Bronowicki, M. Bickel, T. Welzel, S. Susser, S. Zeuzem, C. Sarrazin
Journal: Journal of Hepatology (2018)
HYBRID-APC FOR TREATMENT OF SMALL BOWEL ANGIODYSPLASIA
Authors: S Orlando, F Ferretti, R Penagini, M Vecchi, L Elli
Journal: Endoscopy (2018)

Angiodysplasia are common cause of small bowel bleeding, especially in patients older than 50 years. Argon Plasma coagulation (APC) is reported to be an effective treatment for angiodysplasia in stomach, duodenum, small bowel and colon. Considering the reduced thickness of small bowel wall, it could be safer to lift the mucosa before treatment with APC to reduce the risk of thermal injury and perforation. Hybrid-APC (ERBEJET 2) is a dual system able to lift the mucosa with pressure waterjet prior to thermal coagulation with argon plasma and it is indicated for the Barrett's esophagus ablation.
MicroRNA-193b-3p regulates chondrogenesis and chondrocyte metabolism by targeting HDAC3
Authors: Fangang Meng, Zhiwen Li, Zhiqi Zhang, Zibo Yang, Yan Kang, Xiaoyi Zhao, Dianbo Long, Shu Hu, Minghui Gu, Suiwen He, Peihui Wu, Zongkun Chang, Aishan He, Weiming Liao
Journal: Theranostics (2018)

Histone deacetylase 3 (HDAC3) plays a pivotal role in the repression of cartilage-specific gene expression in human chondrocytes. The aim of this study was to determine whether microRNA-193b-3p (miR-193b-3p) regulates the expression of HDAC3 during chondrogenesis and chondrocyte metabolism. Methods: miR-193b-3p expression was assessed in a human mesenchymal stem cell (hMSC) model of chondrogenesis, in interleukin-1β (IL-1β)-treated primary human chondrocytes (PHCs), and in non-degraded and degraded cartilage. hMSCs and PHCs were transfected with miR-193b-3p or its antisense inhibitor. A direct interaction between miR-193b-3p and its putative binding site in the 3'-untranslated region (3'-UTR) of HDAC3 mRNA was confirmed by performing luciferase reporter assays. Chondrocytes were transfected with miR-193b-3p before performing a chromatin immunoprecipitation assay with an anti-acetylated histone H3 antibody. To investigate miR-193b-3p-transfected PHCs in vivo, they were seeded in tricalcium phosphate-collagen-hyaluronate (TCP-COL-HA) scaffolds, which were then implanted in nude mice. In addition, plasma exosomal miR-193b-3p in samples from normal controls and patients with osteoarthritis (OA) were measured. Results: miR-193b-3p expression was elevated in chondrogenic and hypertrophic hMSCs, while expression was significantly reduced in degraded cartilage compared to non-degraded cartilage. In addition, miR-193b-3p suppressed the activity of reporter constructs containing the 3'-UTR of HDAC3, inhibited HDAC3 expression, and promoted histone H3 acetylation in the COL2A1, AGGRECAN, COMP, and SOX9 promoters. Treatment with the HDAC inhibitor trichostatin A (TSA) increased cartilage-specific gene expression and enhanced hMSCs chondrogenesis. TSA also increased AGGRECAN expression and decreased MMP13 expression in IL-1β-treated PHCs. Further, 8 weeks after implanting PHC-seeded TCP-COL-HA scaffolds subcutaneously in nude mice, we found that miR-193b overexpression strongly enhanced in vivo cartilage formation compared to that found under control conditions. We also found that patients with OA had lower plasma exosomal miR-193b levels than control subjects. Conclusions: These findings indicate that miR-193b-3p directly targets HDAC3, promotes H3 acetylation, and regulates hMSC chondrogenesis and metabolism in PHCs.
Tauroursodeoxycholic acid protects against valproic acid-induced sensitization to acetaminophen hepatotoxicity
Authors: S. Torres, A. Baulies, N. Insausti-Urkia, C. Alarcón-Vila, R. Fucho, E. Solsona, S. Núñez, M.C. Garcia-Ruiz, José Fernandez-Checa
Journal: Journal of Hepatology (2018)
Catalysing the development and introduction of paediatric drug formulations for children living with HIV: a new global collaborative framework for action
Authors: Martina Penazzato, Melynda Watkins, Sébastien Morin, Linda Lewis, Fernando Pascual, Marissa Vicari, Janice Lee, Sally Hargreaves, Meg Doherty, George K Siberry
Journal: The Lancet HIV (2018)
Stereochemistry enhances pharmacological properties of APOC3 antisense oligonucleotides
Authors: L. Apponi, N. Iwamoto, M. Frank-Kamenetsky, H. Yang, M. Braun, A. Shah, D. Butler, G. Lu, V. Vathipadiekal, S. Menon, K. Bowman, L. Pittet, J. Zhang, Z. Zhong, C. Vargeese, S. Standley
Journal: Journal of Hepatology (2018)
ROLE OF EUS IN UNDIAGNOSED PLEURAL EFFUSION
Authors: P Somani, M Sharma
Journal: Endoscopy (2018)

Thoracocentesis is the first diagnostic procedure for pleural effusion (PE). If diagnosis after Thoracocentesis remains uncertain, pleural biopsy either CT/USG guided or thoracoscopy is required for definitive diagnosis. Overall, access to thoracoscopy is limited in many parts of the world, as significant resources and expertise are required. We present the data about evaluation of undiagnosed PE by EUS guided pleural aspiration or FNAC of lymph nodes/pleural deposits. This is first case series regarding EUS guided FNAC of pleural deposits.
Abstract 13814: DMGV is a Novel Marker of Liver Fat and Predicts Future Development of Type 2 Diabetes
Authors: John F O’Sullivan, Jordan E Morningstar, Baohui Zheng, Sarah Jeanfavre, Justin Scott, Qiong Yang, Celine Fernandez, Rakmachandran S Vasan, Michelle T Long, Olle Melander, Thomas J Wang, Caroline Fox, Randall T Peterson, Clary Clish, Kathleen Corey, Robert E Gerszten
Journal: Circulation (2016)

Background: Unbiased “non-targeted” metabolite profiling techniques hold considerable promise for biomarker and pathway discovery, though there have been few successful applications to human disease. We aimed to uncover novel biomarkers of non-alcoholic fatty liver disease (NAFLD) and cardiometabolic disease using non-targeted metabolomic profiling in well-phenotyped human cohorts. Methods: Non-targeted metabolite profiling was performed using hydrophilic interaction chromatography on a UHPLC Q-Exactive hybrid orbitrap LC/MS system. We searched HMDB, Metlin, Chemspider, and Pubchem databases using a 5-ppm mass tolerance for potential identifications of unknown metabolites. Following unambiguous metabolite identification, a high-throughput targeted metabolite assay was generated using a triple quadrupole MS. Stepwise logistic regression was used to determine the association of metabolites with clinical traits and outcomes. Results: The non-targeted platform was applied first to a discovery cohort of 1066 Framingham Heart Study (FHS) Gen 3 participants, of whom 470 underwent a CT scan as part of a comprehensive assessment of adipose depots, including liver fat. An unknown metabolite with a mass/charge ratio of 202.1185 had the strongest association with CT-defined liver fat, which was quantified using the liver-to-phantom ratio (P=1.16E-10, adjusting for age, sex, smoking, alcohol consumption, HDL and triglyceride concentration, HOMA-IR, hypertension, and BMI). Following structural elucidation by LC-MS and the synthesis of a chemical standard, we confirmed the peak identity as α-keto-δ-(N G N G -dimethylguanidino)-valeric acid (DMGV). DMGV was significantly associated with non-alcoholic steatohepatitis (NASH), in a cohort of 36 patients with biopsy-proven NASH and 36 age, sex, and BMI-matched controls (OR=1.96, P=0.011, conditionally adjusted for age, sex, and BMI). Further, DMGV was predictive of future type 2 diabetes mellitus (T2D) in 196 cases of incident diabetes and 126 controls in the Malmo Diet and Cancer Study (OR=1.56, P=8.6E-4, adjusting for age, sex, fasting glucose, and BMI; mean follow-up 12.8 years). Conclusions: DMGV is a novel marker of NAFLD and NASH, and is a predictor of future T2D.
Safety and effectiveness comparing generic and original sofosbuvir-based treatment regimens in patients with hepatitis C: A prospective multicenter study from Argentina
Authors: E. Ridruejo, M. Mendizabal, F. Piñero, C. Alonso, A. Palazzo, M. Sixto, S. Ceballos, C. Gadea, D. Perez, M.V. Reggiardo, V. Moreno, S.E. Mengarelli, A. Bruno, C. Mendoza, J. Vila, F. Barreyro, M.G.V. Zuain, N. Ratusnu, M. Silva
Journal: Journal of Hepatology (2018)
Men have higher mortality in cirrhosis: outcomes by gender and etiology in a large, diverse cohort
Authors: A. Yeluru, M.H. Le, C. Zhao, P. Nguyen, S. Trinh, H. Le, H. Dang, A. Pura, N. Dang, B. Alviar, S. Tran, T. Johnson, A. Le, J. Hoang, M. Nguyen
Journal: Journal of Hepatology (2018)
Spontaneous Regression of Myelomas and of Their Metastatic Growths&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: Margaret Reed Lewis, G. Burroughs Mider
Journal: JNCI Journal of the National Cancer Institute (1941)

Spontaneous Regression of Myelomas and of Their Metastatic Growths Get access Margaret Reed Lewis, Margaret Reed Lewis research associate Department of Embryology, Carnegie Institution of Washington Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Burroughs Mider G. Burroughs Mider research fellow National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 2, Issue 2, October 1941, Pages 123–125, https://doi.org/10.1093/jnci/2.2.123 Published: 01 October 1941
TCTAP A-068 Long-term Outcome of Repeated Alcohol Septal Ablations in Patients with Obstructive Hypertrophic Cardiomyopathy: A Single-centre Experience
Authors: Maksim Kashtanov, Anastasiya Rzannikova, Lev Kardapoltsev, Sergey Chernyshev, Eduard Idov, Valentina Kochmasheva, Igor Kochmashev
Journal: Journal of the American College of Cardiology (2018)
Final report: A phase I trial of BYL719 in combination with gemcitabine and nab-paclitaxel in locally advanced and metastatic pancreatic cancer.
Authors: Heloisa P. Soares, Taymeyah E. Al-Toubah, Richard D. Kim, Jongphil Kim, Neron K Lewis, Amit Mahipal
Journal: Journal of Clinical Oncology (2018)

398 Background: The PI3K/mTOR pathway has emerged as a potential target for anticancer therapy. Considerable evidence suggests that targeting a single isoform of PI3K (p110α) would have sufficient antitumor activity and improved therapeutic window. Further, PI3KCA mutations, gene encoding isoform p110α, are described in pancreatic adenocarcinoma (PAC). BYL719 is an oral class I α-specific PI3K inhibitor that showed preclinical anti-tumor activity. The first in human phase 1 trial of BYL719 defined the maximum tolerated dose (MTD) at 400mg QD. Methods: This was a phase I, single center study (standard 3+3 design). The primary objective was to determine the MTD of BYL719 in combination with gemcitabine (G) and nab-paclitaxel (nabP) as frontline therapy in locally advanced or metastatic PAC. BYL719 was given orally daily (Table). Patients (pts) were restaged q2 cycles. The study was closed prematurely due to slow accrual. Results: Fifteen pts were enrolled (median age was 58 years). Three pts each participated in cohorts 1 and 2. Nine pts were enrolled in cohort 3, but 4 were replaced (3 pts withdrew consent prior to evaluation and 1 missed &gt; 10 days of treatment). One pt in cohort 3 had DLT related to grade 3 nausea and vomiting. A total of 19 grade 3 and 4 adverse events were records as probably or possibly associated with BYL719. The most common ones were hyperglycemia, anemia, and neutrophil count decreased. One pt developed Posterior reversible encephalopathy syndrome (PRES) during cycle 7. Although we could not completely exclude BYL719 as a cause, PRES was attributed to G. One pt had sudden death during cycle 4 that was attributed to progression. Only 8 pts were evaluable for response. Two had stable disease, 5 had partial responses and 1 had progression. The median progression-free survival and overall survival were 5.36 months (1.6 to 10 months) and 8.74 months (3.8 to 21.2 months) respectively. Conclusions: The combination of full doses of G + nabP and BYL719 can be safely administered up to BYL dose of 250 mg/day. Clinical trial information: NCT02155088. [Table: see text]