tbuckley/cabot-search huggingface dataset:
A pharmacokinetic study of gemcitabine at fixed dose rate infusion in patients with impaired hepatic function
Authors: A. Felici, S. Di Segni, S. Colantonio, M. Milella, M. Ciccarese, F. Cecere, B. Nuvoli, G. Ferretti, G. Citro, F. Cognetti
Journal: Journal of Clinical Oncology (2006)

12009 Background: The aim of this study was to evaluate if hepatic dysfunction leads to increased toxicity of gemcitabine (gem) at fixed dose rate, and to characterize the pharmacokinetic (PK) of gem and its major metabolite (2`,2`-difluorodeoxyuridine- 2dFdU) in patients (pts) with normal and altered liver function. Methods: Eight pts with metastatic pancreatic or biliary tract cancer were treated with the followed schedule: gem 1000 mg/m2 at 10/mg/m2/min fixed rate days 1,8, and 15 every 28 days for a maximum of six cycles. Three pts had normal serum bilirubin level and AST level less than two times the upper limit of normal (ULN) (Cohort I); four pts had bilirubin level from 1.6 to 7.0 mg/dL and normal AST level, one pt had serum bilirubin level less than 1.6 mg/dL and AST level greater than two times the ULN (Cohort II). The PK parameters measured were: plasmatic peak concentration (Cmax), area under the plasma concentration-time curve (AUCexp), total plasma clearance (Cl p) and half life (t 1/2 ). Results: Patient characteristics were: median age 62 yrs (range 28–75), male/female 4/4, median cycles cohort I: 6 cycles (3–6), median cycles cohort II: 3 cycles (1–5), median follow-up: 30 weeks (range 3–79) and median weeks of treatment: 14 (1–25). The rate of dose reduction was the same in the two cohorts, as the rate of omitted administrations. Patients with liver dysfunction tolerated gemcitabine without increased toxicity and neither AST nor bilirubin elevation was observed after drug administration. PK parameters were calculated at the first cycle and the results are presented below (see table ). Conclusions: The pharmacokinetics of gemcitabine at fixed dose rate in patients with impaired liver function seems similar to control; no difference between the two cohorts was observed in terms of toxicity and dose reduction. [Table: see text] No significant financial relationships to disclose.
Design of drug-like hepsin inhibitors against prostate cancer and kidney stones
Authors: Vincent Blay, Mu-Chun Li, Sunita P. Ho, Mashall L. Stoller, Hsing-Pang Hsieh, Douglas R. Houston
Journal: Acta Pharmaceutica Sinica B (2019)

Hepsin, a transmembrane serine protease abundant in renal endothelial cells, is a promising therapeutic target against several cancers, particularly prostate cancer. It is involved in the release and polymerization of uromodulin in the urine, which plays a role in kidney stone formation. In this work, we design new potential hepsin inhibitors for high activity, improved specificity towards hepsin, and promising ADMET properties. The ligands were developed in silico through a novel hierarchical pipeline. This pipeline explicitly accounts for off-target binding to the related serine proteases matriptase and HGFA (human hepatocyte growth factor activator). We completed the pipeline incorporating ADMET properties of the candidate inhibitors into custom multi-objective optimization functions. The ligands designed show excellent prospects for targeting hepsin via the blood stream and the urine and thus enable key experimental studies. The computational pipeline proposed is remarkably cost-efficient and can be easily adapted for designing inhibitors against new drug targets.
TCT-310 Outcomes in Patients With Peripheral Vascular Disease After PCI Versus CABG for Left Main Coronary Artery Disease: A Substudy From the EXCEL Trial
Authors: Masahiko Noguchi, Akiko Maehara, Gary Mintz, Ovidiu Dressler, Piet Willem Boonstra, Joseph Sabik, Patrick Serruys, Gregg Stone
Journal: Journal of the American College of Cardiology (2019)
Enhanced Expression of Beta-Catenin and Axl Receptor Tyrosine Kinase (RTK) in Chronic Lymphocytic Leukemia (CLL) B-Cells with Co-Culture on Marrow Stromal Cells: Implications for Leukemic Cell Drug Resistance
Authors: Sutapa Sinha, Charla R Secreto, Justin C. Boysen, Steven L. Warner, David J. Bearss, Asish K Ghosh, Neil E. Kay
Journal: Blood (2018)
TCT-470 Acute Management of Patients With Spontaneous Coronary Artery Dissection: The DISCO (DIssezioni Spontanee COronariche) Italian Registry
Authors: Giorgio Quadri, Enrico Cerrato, Italo Porto, Chiara Cavallino, Luca Bettari, Francesco Tomassini, Alfonso Franzè, Fabio Ferrari, Mario Iannaccone, Marco Pavani, Francesco Rametta, Alessandra Truffa Giachet, Luca Lo Savio, Gianluca Campo, Andrea Demarchi, Cristina Rolfo, Elisabetta Bordoni, Vincenzo Infantino, Chiara Bernelli, Alfonso Gambino, Francesco Cassano, Ferdinando Varbella
Journal: Journal of the American College of Cardiology (2019)
TCT-422 Clinical Outcomes and Predictors of Mortality Among 847 Nonagenarians Undergoing Percutaneous Coronary Intervention: Insights From a Brazilian Nationwide PCI Registry (CENIC Registry)
Authors: Fábio Pinton, Guy Prado, Cristiano Bezerra, Jose Mariani, Carlos Campos, Adriano Caixeta, Marcelo Franken, Pedro A. Lemos
Journal: Journal of the American College of Cardiology (2019)
Multiparametric Cystoscopy for Detection of Bladder Cancer Using Real-time Multispectral Imaging
Authors: Maximilian C. Kriegmair, Jan Rother, Bartłomiej Grychtol, Martin Theuring, Manuel Ritter, Cagatay Günes, Maurice S. Michel, Nikolaos C. Deliolanis, Christian Bolenz
Journal: European Urology (2019)
TCT-331 Correlation Between 3D-QCA–Based FFR and Quantitative Lumen Assessment by IVUS for Left Main Coronary Stenoses: The FAST Left Main Study
Authors: Mariusz Tomaniak, Kaneshka Masdjedi, Laurens Zandvoort, Tara Neleman, Maria Tovar, Alise Vermaire, Janusz Kochman, Miguel Lemmert, Roberto Diletti, Nicolas Van Mieghem, Felix Zijlstra, Joost Daemen
Journal: Journal of the American College of Cardiology (2019)
Targeted next-generation sequencing of circulating-tumor DNA for tracking minimal residual disease in localized colon cancer
Authors: N. Tarazona, F. Gimeno-Valiente, V. Gambardella, S. Zuñiga, P. Rentero-Garrido, M. Huerta, S. Roselló, C. Martinez-Ciarpaglini, J.A. Carbonell-Asins, F. Carrasco, A. Ferrer-Martínez, G. Bruixola, T. Fleitas, J. Martín, R. Tébar-Martínez, D. Moro, J. Castillo, A. Espí, D. Roda, A. Cervantes
Journal: Annals of Oncology (2019)

BackgroundA high percentage of patients diagnosed with localized colon cancer (CC) will relapse after curative treatment. Although pathological staging currently guides our treatment decisions, there are no biomarkers determining minimal residual disease (MRD) and patients are at risk of being undertreated or even overtreated with chemotherapy in this setting. Circulating-tumor DNA (ctDNA) can to be a useful tool to better detect risk of relapse.Patients and methodsOne hundred and fifty patients diagnosed with localized CC were prospectively enrolled in our study. Tumor tissue from those patients was sequenced by a custom-targeted next-generation sequencing (NGS) panel to characterize somatic mutations. A minimum variant allele frequency (VAF) of 5% was applied for variant filtering. Orthogonal droplet digital PCR (ddPCR) validation was carried out. We selected known variants with higher VAF to track ctDNA in the plasma samples by ddPCR.ResultsNGS found known pathological mutations in 132 (88%) primary tumors. ddPCR showed high concordance with NGS (r-=-0.77) for VAF in primary tumors. Detection of ctDNA after surgery and in serial plasma samples during follow-up were associated with poorer disease-free survival (DFS) [hazard ratio (HR), 17.56; log-rank P-=-0.0014 and HR, 11.33; log-rank P-=-0.0001, respectively]. Tracking at least two variants in plasma increased the ability to identify MRD to 87.5%. ctDNA was the only significantly independent predictor of DFS in multivariable analysis. In patients treated with adjuvant chemotherapy, presence of ctDNA after therapy was associated with early relapse (HR 10.02; log-rank P-<-0.0001). Detection of ctDNA at follow-up preceded radiological recurrence with a median lead time of 11.5-months.ConclusionsPlasma postoperative ctDNA detected MRD and identified patients at high risk of relapse in localized CC. Mutation tracking with more than one variant in serial plasma samples improved our accuracy in predicting MRD.
Statin Use and the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B
Authors: Myung Ji Goh, Dong Hyun Sinn, Seonwoo Kim, Sook Young Woo, Hyun Cho, Wonseok Kang, Geum‐Youn Gwak, Yong‐Han Paik, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik
Journal: Hepatology (2019)

Background and Aims Statins have pleiotropic effects that may include chemoprevention. Several observational studies have suggested that statins may prevent hepatocellular carcinoma (HCC), but they have not yet been fully studied in patients with chronic hepatitis B virus (HBV) infections. Approach and Results A hospital‐based retrospective cohort of 7,713 chronic HBV‐infected individuals between January 2008 and December 2012 were analyzed. The primary outcome was the development of HCC. Patients who used statins for at least 28 cumulative defined daily doses during the follow‐up period were defined as statin users (n = 713). The association between the use of statin and the incidence of HCC was analyzed using the multivariable Cox regression model with time‐dependent covariates. During a median follow‐up of 7.2 years (min‐max: 0.5‐9.9), HCC newly developed in 702 patients (9.1%). Statin use was associated with a lower risk of HCC (adjusted hazard ratio = 0.36, 95% confidence interval: 0.19‐0.68, adjusted for age, sex, cirrhosis, diabetes, hypertension, serum alanine aminotransferase, cholesterol, HBV DNA level, antiviral treatment, and antiplatelet therapy). The observed benefit of the statin use was dose‐dependent (adjusted hazard ratio [95% confidence interval], 0.63 [0.31‐1.29]; 0.51 [0.21‐1.25]; 0.32 [0.07,1.36]; and 0.17 [0.06, 0.48] for patients with statin use of 28‐365, 366‐730, 731‐1095, and more than 1,095 cumulative defined daily doses, respectively). In subgroup analysis, the association between statin use and reduced risk of HCC was observed in all prespecified subgroups analyzed. Conclusion Statin use was associated with a reduced risk of HCC development in chronic HBV‐infected patients, suggesting that statins may have a chemopreventive role in this population. These findings warrant a prospective evaluation.
TCT-129 Age Stratified Analysis for Patients With Hypertrophic Cardiomyopathy Undergoing Alcohol Septal Ablation or Septal Myectomy
Authors: Alejandro Lemor, Pedro Villablanca, Gabriel Hernandez, Tarun Jain, Ramandeep Mand, Marvin Eng, Mayra Guerrero, Dee Dee Wang, Igor Palacios, William O'Neill
Journal: Journal of the American College of Cardiology (2019)
Health Status After Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients With Aortic Stenosis
Authors: Suzanne J Baron, Elizabeth A Magnuson, Michael Lu, Kaijun Wang, Khaja Chinnakondepalli, Michael Mack, Vinod H Thourani, Susheel Kodali, Raj Makkar, Howard C Herrmann, Samir Kapadia, Vasilis Babaliaros, Mathew R Williams, Dean Kereiakes, Alan Zajarias, Maria C Alu, John G Webb, Craig R Smith, Martin B Leon, David J Cohen
Journal: Journal of the American College of Cardiology (2019)
Physician Aid-in-Dying for Individuals With Serious Mental Illness: Clarifying Decision-Making Capacity and Psychiatric Futility
Authors: Rocksheng Zhong, Yingcheng Xu, Maria A. Oquendo, Dominic A. Sisti
Journal: The American Journal of Bioethics (2019)

Kious and Battin (2019) describe a pressing and profound ethical dilemma in psychiatry. This dilemma is rooted in conceptual parity—the view that psychiatric illness and somatic illnesses exist wit...
One Year Clinical Experience of the First Commercial Hybrid Closed-Loop System
Authors: Rayhan A. Lal, Marina Basina, David M. Maahs, Korey Hood, Bruce Buckingham, Darrell M. Wilson
Journal: Diabetes Care (2019)

In September 2016, the U.S. Food and Drug Administration approved the Medtronic 670G "hybrid" closed-loop system. In Auto Mode, this system automatically controls basal insulin delivery based on continuous glucose monitoring data but requires users to enter carbohydrates and blood glucose for boluses. To track real-world experience with this first commercial closed-loop device, we prospectively followed pediatric and adult patients starting the 670G system.
TCT-465 Automatic Identification and Quantification of the Mitral Annulus for Consistent TMVR Planning: A Preliminary Study
Authors: Patricia Lopes, Roel Wirix-Speetjens, Jan Sijbers, Jos Vander Sloten, Johan Bosmans, Paul Van Herck, Janelle Schrot
Journal: Journal of the American College of Cardiology (2019)
TCT-530 Late Onset of New Conduction Disturbances Requiring Permanent Pacemaker Implantation Following Transcatheter Aortic Valve Implantation
Authors: Nynke Kooistra, Martijn van Mourik, Ramon Rodríguez-Olivares, Alexander Maass, Vincent Nijenhuis, Hindrik van der Werf, Jurrien Ten Berg, Adriaan Kraaijeveld, Jan Baan, Michiel Voskuil, Marije Vis, Pieter Stella
Journal: Journal of the American College of Cardiology (2019)
TCT-290 Outcomes After Revascularization With a Polymer-Free Biolimus-Eluting BioFreedom Stent or a Biodegradable Polymer Ultrathin Strut Sirolimus-Eluting Orsiro Stent in Patients With and Without Acute Coronary Syndromes: From the SORT OUT IX Trial
Authors: Christian Fallesen, Evald Christiansen, Bent Raungaard, Michael Maeng, Julia Ellert, Christian Terkelsen, Martin Kirk Christensen, Anders Junker, Steen Dalby Kristensen, Henrik Hansen, Svend Eggert Jensen, Johnny Kahlert, Jens Lassen, Lisette Okkels Jensen
Journal: Journal of the American College of Cardiology (2019)
TCT-522 Single Tertiary Center U.K. Experience Across 2 Large Sites For Patients Presenting as Out-of-Hospital Cardiac Arrests (OHCAs)
Authors: Denise Tiong, Sharmaine Thiru, David Lai Chin Kon, Adeogo Olusan, Hussain Contractor, Farzin Fath-Ordoubadi
Journal: Journal of the American College of Cardiology (2019)
Lung adenocarcinoma-intrinsic GBE1 signaling inhibits anti-tumor immunity
Authors: Lifeng Li, Li Yang, Shiqi Cheng, Zhirui Fan, Zhibo Shen, Wenhua Xue, Yujia Zheng, Feng Li, Dong Wang, Kai Zhang, Jingyao Lian, Dan Wang, Zijia Zhu, Jie Zhao, Yi Zhang
Journal: Molecular Cancer (2019)

Changes in glycogen metabolism is an essential feature among the various metabolic adaptations used by cancer cells to adjust to the conditions imposed by the tumor microenvironment. Our previous study showed that glycogen branching enzyme (GBE1) is downstream of the HIF1 pathway in hypoxia-conditioned lung cancer cells. In the present study, we investigated whether GBE1 is involved in the immune regulation of the tumor microenvironment in lung adenocarcinoma (LUAD). We used RNA-sequencing analysis and the multiplex assay to determine changes in GBE1 knockdown cells. The role of GBE1 in LUAD was evaluated both in vitro and in vivo. GBE1 knockdown increased the expression of chemokines CCL5 and CXCL10 in A549 cells. CD8 expression correlated positively with CCL5 and CXCL10 expression in LUAD. The supernatants from the GBE1 knockdown cells increased recruitment of CD8+ T lymphocytes. However, the neutralizing antibodies of CCL5 or CXCL10 significantly inhibited cell migration induced by shGBE1 cell supernatants. STING/IFN-I pathway mediated the effect of GBE1 knockdown for CCL5 and CXCL10 upregulation. Moreover, PD-L1 increased significantly in shGBE1 A549 cells compared to those in control cells. Additionally, in LUAD tumor tissues, a negative link between PD-L1 and GBE1 was observed. Lastly, blockade of GBE1 signaling combined with anti-PD-L1 antibody significantly inhibited tumor growth in vivo. GBE1 blockade promotes the secretion of CCL5 and CXCL10 to recruit CD8+ T lymphocytes to the tumor microenvironment via the IFN-I/STING signaling pathway, accompanied by upregulation of PD-L1 in LUAD cells, suggesting that GBE1 could be a promising target for achieving tumor regression through cancer immunotherapy in LUAD.
Quality of Life in Cancer Patients Undergoing Anticoagulant Treatment for Venous Thromboembolism: The Quavitec Study
Authors: Dominique Farge, Nicolas Falvo, Matthieu Resche-Rigon, Toufek Berremili, Francis Couturaud, Okba Bensaoula, Lionel Védrine, Isabelle Bonnet, Denis Péré-Vergé, Marie Coudurier, Veronique Li, Francis Cajfinger
Journal: Blood (2016)
Real-world single-center experience with 10 cases of generalized pustular psoriasis successfully treated with ixekizumab
Authors: Mayumi Nagata, Masahiro Kamata, Saki Fukaya, Kotaro Hayashi, Atsuko Fukuyasu, Takamitsu Tanaka, Takeko Ishikawa, Takamitsu Ohnishi, Kazumitsu Sugiura, Yayoi Tada
Journal: Journal of the American Academy of Dermatology (2019)
Responding to Implicit Bias in Abusive Head Trauma Evaluations and Reporting in the PICU: Ethical Consideration During a Clinical Trial
Authors: Jennifer B. McCormick, Kent P. Hymel
Journal: The American Journal of Bioethics (2019)

"Responding to Implicit Bias in Abusive Head Trauma Evaluations and Reporting in the PICU: Ethical Consideration During a Clinical Trial." The American Journal of Bioethics, 19(10), pp. 114–115
TCT-385 The MADS Classification in Patients Undergoing Left Main Percutaneous Coronary Intervention: Technique Analysis From the IDEAL LM Trial
Authors: Chun-Chin Chang, Yoshinobu Onuma, Maciej Lesiak, Evgeny Merkulov, Richard Anderson, Evgeny Kretov, Paul Barragan, Keith Oldroyd, Robert-Jan Van Geuns
Journal: Journal of the American College of Cardiology (2019)
Advances in Disease Mechanisms and Translational Technologies: Clinicopathologic Significance of Inflammasome Activation in Autoimmune Diseases
Authors: J. Michelle Kahlenberg, Insoo Kang
Journal: Arthritis & Rheumatology (2019)

Autoimmune diseases are characterized by dysregulated immune tolerance to self and inflammatory damage to tissues and organs. The development of inflammation involves multiple innate and adaptive immune pathways. Inflammasomes are multimeric cytosolic protein complexes that form to mediate host immune responses upon recognizing pathogen- or damage-associated molecular patterns via pattern-recognition receptors (PRRs). The accelerating pace of inflammasome research has demonstrated important roles for inflammasome activation in many pathologic conditions, including infectious, metabolic, autoinflammatory, and autoimmune diseases. The inflammasome generally comprises a PRR, procaspase 1, and an adaptor molecule connecting the PRR and procaspase 1. Upon inflammasome activation, procaspase 1 becomes active caspase 1 that converts pro-interleukin-1β (proIL-1β) and proIL-18 into mature and active IL-1β and IL-18, respectively. The cytokines IL-1β and IL-18 have multipotent effects on immune and nonimmune cells and induce and promote systemic and local inflammatory responses. Human studies have shown increased levels of these cytokines, altered activation of inflammasome-related molecules, and/or the presence of inflammasome activators in rheumatic diseases, including systemic lupus erythematosus, rheumatoid arthritis, crystal-induced arthropathies, and Sjögren's syndrome. Such changes are found in the primary target organs, such as the kidneys, joints, and salivary glands, as well as in the cardiovascular system. In animal models of rheumatic diseases, inflammation and tissue damage improve upon genetic or pharmacologic targeting of the inflammasome, supporting its pathogenic role. Herein, we review the clinicopathologic significance and therapeutic targeting of inflammasome activation in rheumatic diseases and related conditions based on recent findings.
TCT-627 Novel Sirolimus Eluting Stent With Fusion Coating Technology to Address the “Diabetes Issue”: 2-Year Result of the en-ABL e-Registry
Authors: Luca Testa, Sameer Dani, Devang Desai, Rashmit Pandya, Pritesh Parekh, Apurva Vasavada, Nirav Bhalani, Chirag Sheth, Dinesh Shah
Journal: Journal of the American College of Cardiology (2019)
TCT-338 Electrical Microcurrent Therapy for Treatment of Chronic Systolic Heart Failure: Animal and First-in-Man Data
Authors: L. Christian Napp, Guenes Dogan, Jasmin Hanke, Silvia Mariani, Peter Göttel, Kersten Brandes, Samir Sarikouch, Christoph Bara, Johannes Müller, Jan Schmitto
Journal: Journal of the American College of Cardiology (2019)
TCT-159 Clinical Significance of Elevated Preprocedural Hemoglobin Level as a Marker of Outcomes After Percutaneous Coronary Intervention
Authors: Byung Gyu Kim, Byeong-Keuk Kim, Sung-Jin Hong, Chul-Min Ahn, Dong-Ho Shin, Jung-Sun Kim, Young-Guk Ko, Donghoon Choi, Myeong-Ki Hong, Yangsoo Jang, Byoung Kwon Lee
Journal: Journal of the American College of Cardiology (2019)
TCT-797 Clinical Outcome in Femoral Access of High Volume Radial Percutaneous Coronary Intervention Center in Patients With ST-Segment Elevation Myocardial Infarction
Authors: Hyeon Jeong Kim, Jang Hoon Lee, Bo Eun Park, Hong Nyun Kim, Se Yong Jang, Myung Hwan Bae, Dongheon Yang, Hun Sik Park, Yongkeun Cho, Shung Chull Chae, Myung Ho Jeong
Journal: Journal of the American College of Cardiology (2019)
Treatment-Related Morbidity and Mortality Associated with Remission Induction in Adolescent and Young Adult (AYA) Versus Young Adult Patients with Newly Diagnosed Acute Myeloid Leukemia (AML)
Authors: Cory Michael Vela, Viet Q. Ho, Justina Ofori Frimpong, Bryan Brinda, Timothy George, Kendra L. Sweet, Eric Padron, David Sallman, Alan F List, Jeffrey E. Lancet, Rami S. Komrokji
Journal: Blood (2016)
Modeling Cellular Response in Large-Scale Radiogenomic Databases to Advance Precision Radiotherapy
Authors: Venkata SK. Manem, Meghan Lambie, Ian Smith, Petr Smirnov, Victor Kofia, Mark Freeman, Marianne Koritzinsky, Mohamed E. Abazeed, Benjamin Haibe-Kains, Scott V. Bratman
Journal: Cancer Research (2019)

Abstract Radiotherapy is integral to the care of a majority of patients with cancer. Despite differences in tumor responses to radiation (radioresponse), dose prescriptions are not currently tailored to individual patients. Recent large-scale cancer cell line databases hold the promise of unravelling the complex molecular arrangements underlying cellular response to radiation, which is critical for novel predictive biomarker discovery. Here, we present RadioGx, a computational platform for integrative analyses of radioresponse using radiogenomic databases. We fit the dose–response data within RadioGx to the linear-quadratic model. The imputed survival across a range of dose levels (AUC) was a robust radioresponse indicator that correlated with biological processes known to underpin the cellular response to radiation. Using AUC as a metric for further investigations, we found that radiation sensitivity was significantly associated with disruptive mutations in genes related to nonhomologous end joining. Next, by simulating the effects of different oxygen levels, we identified putative genes that may influence radioresponse specifically under hypoxic conditions. Furthermore, using transcriptomic data, we found evidence for tissue-specific determinants of radioresponse, suggesting that tumor type could influence the validity of putative predictive biomarkers of radioresponse. Finally, integrating radioresponse with drug response data, we found that drug classes impacting the cytoskeleton, DNA replication, and mitosis display similar therapeutic effects to ionizing radiation on cancer cell lines. In summary, RadioGx provides a unique computational toolbox for hypothesis generation to advance preclinical research for radiation oncology and precision medicine. Significance: The RadioGx computational platform enables integrative analyses of cellular response to radiation with drug responses and genome-wide molecular data.