tbuckley/cabot-search huggingface dataset:
Genomic Aberrations and Late Recurrence in Postmenopausal Women with Hormone Receptor–positive Early Breast Cancer: Results from the SOLE Trial
Authors: Elena Guerini-Rocco, Kathryn P. Gray, Caterina Fumagalli, Marta Rita Reforgiato, Isabella Leone, Paola Rafaniello Raviele, Elisabetta Munzone, Roswitha Kammler, Patrick Neven, Erika Hitre, Guy Jerusalem, Edda Simoncini, Andrea Gombos, Ines Deleu, Per Karlsson, Stefan Aebi, Jacquie Chirgwin, Vincenzo Di Lauro, Alastair Thompson, Marie-Pascale Graas, Matthew Barber, Christel Fontaine, Sibylle Loibl, Joaquín Gavilá, Katsumasa Kuroi, Bettina Müller, Seamus O’Reilly, Angelo Di Leo, Aron Goldhirsch, Giuseppe Viale, Massimo Barberis, Meredith M. Regan, Marco Colleoni
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Women with hormone receptor–positive early breast cancers have a persistent risk of relapse and biomarkers for late recurrence are needed. We sought to identify tumor genomic aberrations associated with increased late-recurrence risk. Experimental Design: In a secondary analysis of Study of Letrozole Extension trial, a case-cohort–like sampling selected 598 primary breast cancers for targeted next-generation sequencing analysis of gene mutations and copy-number gains (CNGs). Correlations of genomic aberrations with clinicopathologic factors and breast and distant recurrence-free intervals (BCFIs and DRFIs) were analyzed using weighted Cox models. Results: Analysis of mutations and CNGs was successfully performed for 403 and 350 samples, including 148 and 134 patients with breast cancer recurrences (median follow-up time, 5.2 years), respectively. The most frequent alterations were PIK3CA mutations (42%) and CNGs of CCND1 (15%), ERBB2 (10%), FGFR1 (8%), and MYC (8%). PIK3CA mutations and MYC CNGs were associated with lower (P = 0.03) and higher (P = 0.004) tumor grade, respectively; a higher Ki-67 was seen in tumor with CCND1, ERBB2, and MYC CNGs (P = 0.01, P &amp;lt; 0.001, and P = 0.03, respectively). FGFR1 CNG was associated with an increased risk of late events in univariate analyses [17/29 patients; BCFI: HR, 3.2; 95% confidence interval (CI), 1.48–6.92; P = 0.003 and DRFI: HR, 3.5; 95% CI, 1.61–7.75; P = 0.002) and in multivariable models adjusted for clinicopathologic factors. Conclusions: Postmenopausal women with hormone receptor–positive early breast cancer harboring FGFR1 CNG had an increased risk of late recurrence despite extended therapy. FGFR1 CNG may represent a useful prognostic biomarker for late recurrence and a therapeutic target.
Abstract 13898: Estrogen-Related Receptor Signaling is Critical for Postnatal Cardiac Maturation
Authors: Timothy R Matsuura, Tomoya Sakamoto, David M Ryba, Shibiao Wan, Daniel P Kelly
Journal: Circulation (2019)

Fetal to adult cardiac maturation involves a mitochondrial biogenic and maturation response marked by an increased capacity for fatty acid oxidation (FAO). In parallel, cardiac energy-consuming mac...
A phase II study of dose-dense temozolomide and lapatinib for recurrent low-grade and anaplastic supratentorial, infratentorial, and spinal cord ependymoma
Authors: Mark R Gilbert, Ying Yuan, Jimin Wu, Tito Mendoza, Elizabeth Vera, Antonio Omuro, Frank Lieberman, H Ian Robins, Elizabeth R Gerstner, Jing Wu, Patrick Y Wen, Tom Mikkelsen, Kenneth Aldape, Terri S Armstrong
Journal: Neuro-Oncology (2020)

No standard medical treatment exists for adult patients with recurrent ependymoma, and prospective clinical trials in this population have not succeeded because of its rarity and challenges in accruing patients. The Collaborative Ependymoma Research Network conducted a prospective phase II clinical trial of dose-dense temozolomide (TMZ) and lapatinib, targeting the unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter status and increased expression of ErbB2 (human epidermal growth factor receptor 2) and ErbB1 (epidermal growth factor receptor) in ependymomas.Patients age 18 or older with histologically proven and progressive ependymoma or anaplastic ependymoma were eligible and received dose-dense TMZ and daily lapatinib. The primary outcome measure was median progression-free survival (PFS). Landmark 6- and 12-month PFS and objective response were measured. Serial assessments of symptom burden using the MD Anderson Symptom Inventory Brain Tumor (MDASI-BT)/MDASI-Spine Tumor modules were collected.The 50 patients enrolled had a median age of 43.5 years, median Karnofsky performance status of 90, and a median of 2 prior relapses. Twenty patients had grade III, 16 grade II, and 8 grade I ependymoma. Half had spinal cord tumors; 15 had a supratentorial tumor, 8 infratentorial, and 2 had disseminated disease. Treatment was well tolerated. The median PFS was 7.8 months (95% CI: 5.5,12.2); the 6- and 12-month PFS rates were 55% and 38%, with 2 complete and 6 partial responses. Measures of symptom burden showed reduction in moderate-severe pain and other disease-related symptoms in most patients.This treatment, with demonstrated clinical activity with objective responses and prolonged disease control associated with disease-related symptom improvements, is an option as a salvage regimen for adult patients with recurrent ependymoma.
Transcriptional profile of platelets and iPSC-derived megakaryocytes from whole-genome and RNA sequencing
Authors: Kai Kammers, Margaret A. Taub, Benjamin Rodriguez, Lisa R. Yanek, Ingo Ruczinski, Joshua Martin, Kanika Kanchan, Alexis Battle, Linzhao Cheng, Zack Z. Wang, Andrew D. Johnson, Jeffrey T. Leek, Nauder Faraday, Lewis C. Becker, Rasika A. Mathias
Journal: Blood (2020)
TCT CONNECT-2 The PASCAL Transcatheter Valve Repair System for the Treatment of Tricuspid Regurgitation: 30-Day Outcomes From the CLASP TR Early Feasibility Study
Authors: Susheel Kodali, Rebecca Hahn, Mackram Eleid, Robert Kipperman, Robert Smith, Scott Lim, William Gray, Akhil Narang, Sorin Pislaru, Konstantinos Koulogiannis, Paul Grayburn, Dale Fowler, Katie Hawthorne, Abdellaziz Dahou, Charles Davidson
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-409 Mechanisms of Multi layer In-Stent Restenosis Assessed by Optical Coherence Tomography
Authors: Musa Sharkawi, Mordechai Golomb, Chidalu Mozie, Mickayla Royer, Barbora Zvarova, Phillip M. Devlin, Brian Bergmark, Kevin Croce
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-400 Residual Functional SYNTAX Score by Quantitative Flow Ratio and Improvement of Exercise Capacity After Revascularization
Authors: Seung Hun Lee, Joo Myung Lee, Ki Hong Choi, Doosup Shin, Doyeon Hwang, Hyun Kuk Kim, Joon-Hyung Doh, Chang-Wook Nam, Eun-Seok Shin, Mi Ja Jang, Se Young Im, Taek Kyu Park, Jeong Hoon Yang, Young Bin Song, Joo-Yong Hahn, Seung-Hyuk Choi, Bon-Kwon Koo, Hyeon-Cheol Gwon
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-370 A Patient-Level, Pooled Analysis of Mortality Rates With the Passeo-18 Lux Paclitaxel Drug-Coated Balloon in Peripheral Arterial Disease
Authors: Brian Forrestal, Cheng Zhang, Brian Case, Charan Yerasi, Rebecca Torguson, Ron Waksman
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-132 The Relationship Between Eccentricity Index and Hemodynamic Performance in Patients Undergoing Transcatheter Aortic Valve Replacement With Balloon Expandable Valve
Authors: Marouane Boukhris, Jessica Forcillo, Jeannot Potvin, Malek Badreddine, Ali Hillani, Nicolas Noiseux, Louis-Mathieux Stevens, Jean-François Gobeil, Jean-Bernard Masson
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-263 A Novel Risk Score to Predict 1-Year Mortality in Patients Undergoing Complex High-Risk Indicated Percutaneous Coronary Intervention (CHIP PCI)
Authors: Sorin Brener, Gregory Cunn, Pankil Desai, Mouzamjha Faroqui, Le Dung Ha, Garima Handa, Issa Kutkut, Adnan Raza, Terrence Sacchi
Journal: Journal of the American College of Cardiology (2020)
Preventing the Spread of SARS-CoV-2 With Masks and Other “Low-tech” Interventions
Authors: Andrea M. Lerner, Gregory K. Folkers, Anthony S. Fauci
Journal: JAMA (2020)

Xiaowen Wang, MD; Enrico G. Ferro, MD; Guohai Zhou, PhD; Dean Hashimoto, MD, JD; Deepak L. Bhatt, MD, MPH
TCT CONNECT-90 Procedural Characteristics and Late Outcomes of Percutaneous Coronary Intervention in the Workup Pre-TAVR
Authors: Laurent Faroux, Francisco Campelo Parada, Erika Munoz-Garcia, Luis Nombela-Franco, Quentin Fischer, Pierre Donaint, Vicenc Serra, Gabriela Veiga Fernández, Enrique Gutierrez Ibanes, Victoria Vilalta, Alberto Alperi, Ander Regueiro, Lluis Asmarats, Henrique Ribeiro, Anthony Matta, Antonio Munoz-Garcia, German Armijo Ortiz, Marina Urena, Damien Metz, Eduard Rodenas-Alesina, Jose Maria De La Torre Hernandez, Eduard Fernandez-Nofrerias, Isaac Pascual, Pedro Pérez Fuentes, Dabit Arzamendi, Diego Carter Campanha Borges, David del Val, Thomas Couture, Josep Rodés-Cabau
Journal: Journal of the American College of Cardiology (2020)
Obese patients with NASH have increased hepatic expression of SARS-CoV-2 critical entry points
Authors: Marcos F. Fondevila, Maria Mercado-Gómez, Amaia Rodríguez, Maria J. Gonzalez-Rellan, Paula Iruzubieta, Víctor Valentí, Javier Escalada, Markus Schwaninger, Vincent Prevot, Carlos Dieguez, Javier Crespo, Gema Frühbeck, Maria L. Martinez-Chantar, Ruben Nogueiras
Journal: Journal of Hepatology (2020)
Mitochondrial antiviral signaling protein is crucial for the development of pulmonary fibrosis
Authors: Sang-Hun Kim, Jung Yeon Lee, Chang Min Yoon, Hyeon Jun Shin, Sei Won Lee, Ivan Rosas, Erica Herzog, Charles S. Dela Cruz, Naftali Kaminski, Min-Jong Kang
Journal: European Respiratory Journal (2020)

Danger signals, or damage-associated molecular patterns (DAMPs), instigate mitochondrial innate immune responses wherein mitochondrial antiviral signaling protein (MAVS) functions as a key platform molecule to mediate them. The role of MAVS in the pathogenesis of idiopathic pulmonary fibrosis (IPF), however, has not yet been identified. Whether MAVS signalling can be modulated by currently existing drugs has also not been explored. We used an established model of pulmonary fibrosis to demonstrate that MAVS is a critical mediator of multiple DAMP signalling pathways and the consequent lung fibrosis after bleomycin-induced injury in vivo . After bleomycin injury, MAVS expression was mainly observed in macrophages. Multimeric MAVS aggregation, a key event of MAVS signalling activation, was significantly increased and persisted in bleomycin-injured lungs. A proapoptotic BH3 mimetic, ABT-263, attenuated the expression of MAVS and its signalling and, consequently, the development of experimental pulmonary fibrosis. In contrast, the therapeutic effects of nintedanib and pirfenidone, two drugs approved for IPF treatment, were not related to the modulation of MAVS or its signalling. Multimeric MAVS aggregation was significantly increased in lungs from IPF patients as well. MAVS may play an important role in the development of pulmonary fibrosis, and targeting MAVS with BH3 mimetics may provide a novel and much needed therapeutic strategy for IPF.
TCT CONNECT-398 Prognostic Implications of Post-Intervention Resting Pd/Pa and Fractional Flow Reserve in Patients With Stent Implantation
Authors: Doosup Shin, Seung Hun Lee, Joo Myung Lee, Ki Hong Choi, Doyeon Hwang, Hyunjong Lee, Ho-Jun Jang, Hyun Kuk Kim, Jae-Jin Kwak, Sang Jin Ha, Young Bin Song, Eun-Seok Shin, Joon-Hyung Doh
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-285 Quantitative Analysis of Intracoronary Calcium Fracture and Tissue Dissection Using Finite Element Modeling and Optical Coherence Tomography Imaging
Authors: Vladislav Zimin, Pengfei Dong, Luis Augusto Dallan, Juhwan Lee, Yazan Gharaibeh, Linxia Gu, Hiram Bezerra, David Wilson
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-411 IVUS Characteristics of Stent Edge Hematoma Associated With Acute Occlusion
Authors: Ge Jin, Gary Mintz, Ziad Ali, Ajay Kirtane, Leroy Rabbani, Sahil A. Parikh, Martin Leon, Dimitrios Karmpaliotis, Jeffrey Moses, Akiko Maehara
Journal: Journal of the American College of Cardiology (2020)
Resistance-Conferring Mycobacterial Mutations and Quantification of Early Bactericidal Activity
Authors: Solomon P. le Roux, Caryn Upton, Naadira Vanker, Kelly E. Dooley, Andreas H. Diacon, Sachiko Miyahara, Florian von Groote-Bidlingmaier, Xin Sun, Richard Hafner, Susan L. Rosenkranz, Elisa H. Ignatius, Eric L. Nuermberger, Laura Moran, Kathleen Donahue, Susan Swindells, Rachel Issa, Christopher Lane, Mark Lojacono, Rachel Mahachi, William Murtaugh, Lynette Purdue, Akbar Shahkolahi, Ronald Ssenyonga
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

"Resistance-Conferring Mycobacterial Mutations and Quantification of Early Bactericidal Activity." American Journal of Respiratory and Critical Care Medicine, 203(5), pp. 635–637
TCT CONNECT-203 Prediction of Functional Severity of Coronary Bifurcation Lesions by Means of Angiographically Derived Score (Results From FIESTA Registry, NCT01724957)
Authors: Dobrin Vassilev, Niya Mileva, Carlos Collet, Pavel Nikolov, Georgi Dimitrov, Kiril Karamfiloff, Vladimir Naunov, Gianluca Rigatelli, Robert Gil, Patrick Serruys
Journal: Journal of the American College of Cardiology (2020)
The Robot in General Surgery—Change Is the Only Constant
Authors: Ann M. Defnet, S. Scott Davis
Journal: JAMA Surgery (2020)

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Establishment of a highly efficient gene transfer system for mouse fetal hepatic progenitor cells
Authors: Kentaro Yasuchika, Tetsuro Hirose, Hideaki Fujii, Shoshiro Oe, Koichi Hasegawa, Takahisa Fujikawa, Hisaya Azuma, Yoshio Yamaoka
Journal: Hepatology (2002)

Because of a donor shortage problem in liver transplantation, cell transplantation has been anticipated as a useful bridge or substitute therapy, and has necessitated the development of cell sources other than donated organs. Therefore, the use of fetal hepatic progenitor cells (HPCs) is now being focused on. In this study, we intended to establish an efficient ex vivo nonviral gene-transfer system using a newly developed isolation and culture system for mouse fetal HPCs. Fetal HPCs, characterized using immunocytochemistry and reverse-transcription polymerase chain reaction (RT-PCR) for lineage markers, were collected from E13.5 Balb/c mice using change in size because of cell aggregation by their homophilic cell-to-cell binding occurring during suspension culture. Optimal conditions for culture and ex vivo gene transfection for fetal HPCs were determined by 3 H-thymidine incorporation and the expression efficacy of transfected red fluorescent protein (DsRed) gene in different culture media. The optimum timing for gene transfection was also evaluated. To evaluate the in vivo expression of the transferred gene, DsRed-transferred fetal HPCs were transplanted into 70% partially hepatectomized allogenic mice. The highest efficacy of DsRed gene transfection into fetal HPCs in vitro (45% ± 12.3%) was achieved with culture media, which also enabled the highest 3 H-thymidine incorporation, containing the deleted form of hepatocyte growth factor (dHGF) and insulin, and when transfection was performed immediately after isolation. In vivo DsRed expression in fetal HPCs was maintained concomitantly with albumin expression even after HPC transplantation. In conclusion, we established a highly efficient in vitro gene transfer system for mouse fetal HPCs using a newly developed isolation and culture system. (Hepatology2002;36:1488-1497).
Local delivery of CAR T cells targeting fibroblast activation protein is safe in patients with pleural mesothelioma: first report of FAPME, a phase I clinical trial
Authors: S. Hiltbrunner, C. Britschgi, P. Schuberth, L. Bankel, T.D.L. Nguyen-Kim, P. Gulati, W. Weder, I. Opitz, O. Lauk, C. Caviezel, H. Bachmann, A. Tabor, P. Schröder, A. Knuth, C. Münz, R. Stahel, O. Boyman, C. Renner, U. Petrausch, A. Curioni-Fontecedro
Journal: Annals of Oncology (2020)
TCT CONNECT-301 Incidence, Predictors, and Impact of Readmissions Following PCI and CABG for Left Main Coronary Artery Disease: Analysis From the EXCEL Trial
Authors: Ioanna Kosmidou, Bahira Shahim, Zixuan Zhang, Ovidiu Dressler, Bjorn Redfors, Marie-Claude Morice, David Kandzari, Dimitri Karmpaliotis, William Brown, Nicholas Lembo, Adrian Banning, Patrick Serruys, Gregg Stone
Journal: Journal of the American College of Cardiology (2020)
Multicentre testing of the EUCAST broth microdilution reference method for MIC determination on Mycobacterium tuberculosis
Authors: Thomas Schön, Jim Werngren, Diana Machado, Emanuele Borroni, Maria Wijkander, Gerard Lina, Johan Mouton, Erika Matuschek, Gunnar Kahlmeter, Christian Giske, Miguel Santin, Daniela Maria Cirillo, Miguel Viveiros, Emmanuelle Cambau
Journal: Clinical Microbiology and Infection (2020)

The first objective of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) subcommittee for antimycobacterial susceptibility testing (AMST), launched in 2016, was to set a reference method for determining the MICs of antituberculous agents, since many protocols are used worldwide and a consensus one is needed for the determination of microbiological breakpoints.During 2017 and 2018, MIC determination protocols were evaluated prospectively in a multicentre study within the four AMST laboratories. MIC results were obtained for isoniazid, levofloxacin and amikacin on the reference strain Mycobacterium tuberculosis H37Rv ATCC 27294. Broth microdilution (BMD) in Middlebrook 7H9 and solid medium dilution (SMD) in Middlebrook 7H10 were performed using two inoculum concentrations. MICs were interpreted with regard to visual and 99% inhibition after 7, 14 or 21 days of incubation for BMD and 21 days for SMD.Following the EUCAST reference protocol, intra- and inter-assay agreements were within ±1 MIC dilution for >95% of the observations for the three drugs in both methods. MIC values, presented as MIC mode (range) for BMD and SMD respectively, were: 0.03 (0.015-0.06) mg/L and 0.12 (0.06-0.25) mg/L for isoniazid, 0.25 mg/L (0.25-0.5) and 0.5 mg/L (0.12-0.5) for levofloxacin, and 0.5 mg/L (0.5-1.0) and 0.5 mg/L (0.5-1.0) for amikacin.Both SMD and BMD were reproducible and eligible as a reference method for MIC determination of the Mycobacterium tuberculosis complex (MTBC). BMD was finally selected as the EUCAST reference method. From now on it will be used to set epidemiological cut-off values and clinical breakpoints of new and old antituberculous agents.
Perifosine induces differentiation and cell death in prostate cancer cells
Authors: Daniel Floryk, Timothy Thompson
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

1481 

We analyzed the mechanism of action for perifosine (D-21266) a new synthetic alkylphospholipid Akt inhibitor using LNCaP and PC-3 prostate cancer cells. Perifosine treatment of PC-3 cells resulted in cytostatic and cytotoxic effects. Cytostatic effects were characterized by cell growth arrest, cell cycle block and morphological changes, such as a cell enlargement and granulation, hallmarks of differentiating PC-3 cells. Specific differentiation markers including prostasomal, secretory and plasma membrane proteins, and keratins were induced by perifosine. Among them, we detected strong induction and secretion of CEACAM5 protein. In contrast, perifosine strongly reduced caveolin-1 RNA levels. Cytotoxic effects included para-apoptosis, apoptosis, and necrosis. To pursue the mechanisms responsible for these activities we focused on signaling pathways that lie downstream of Akt. Perifosine-triggered GSK-3β activation in PC-3 and LNCaP cells resulted in the expression of GSK-3β-related differentiation markers. This expression was reduced in the presence of specific siRNA for GSK-3β or for its target CREB protein. The use of the GSK-3β inhibitor lithium chloride indicated that GSK-3β partially protects prostate cancer cells from the cytotoxic effects of perifosine. Together, these findings indicate that perifosine induces GSK-3β-related differentiation and caspase-independent cell death in prostate cancer PC-3 cells. In addition our results identify specific biomarkers for perifosine therapy.
Unacylated-Ghrelin Impairs Hippocampal Neurogenesis and Memory in Mice and Is Altered in Parkinson’s Dementia in Humans
Authors: Amanda K.E. Hornsby, Luke Buntwal, Maria Carla Carisi, Vanessa V. Santos, Fionnuala Johnston, Luke D. Roberts, Martina Sassi, Mathieu Mequinion, Romana Stark, Alex Reichenbach, Sarah H. Lockie, Mario Siervo, Owain Howell, Alwena H. Morgan, Timothy Wells, Zane B. Andrews, David J. Burn, Jeffrey S. Davies
Journal: Cell Reports Medicine (2020)

Blood-borne factors regulate adult hippocampal neurogenesis and cognition in mammals. We report that elevating circulating unacylated-ghrelin (UAG), using both pharmacological and genetic methods, reduced hippocampal neurogenesis and plasticity in mice. Spatial memory impairments observed in ghrelin-O-acyl transferase-null (GOAT-/-) mice that lack acyl-ghrelin (AG) but have high levels of UAG were rescued by acyl-ghrelin. Acyl-ghrelin-mediated neurogenesis in vitro was dependent on non-cell-autonomous BDNF signaling that was inhibited by UAG. These findings suggest that post-translational acylation of ghrelin is important to neurogenesis and memory in mice. To determine relevance in humans, we analyzed circulating AG:UAG in Parkinson disease (PD) patients diagnosed with dementia (PDD), cognitively intact PD patients, and controls. Notably, plasma AG:UAG was only reduced in PDD. Hippocampal ghrelin-receptor expression remained unchanged; however, GOAT+ cell number was reduced in PDD. We identify UAG as a regulator of hippocampal-dependent plasticity and spatial memory and AG:UAG as a putative circulating diagnostic biomarker of dementia.