tbuckley/cabot-search huggingface dataset:
A roadmap for zoonotic tuberculosis: a One Health approach to ending tuberculosis
Authors: Anna S Dean, Simona Forcella, Francisco Olea-Popelka, Ahmed El Idrissi, Philippe Glaziou, Amina Benyahia, Elizabeth Mumford, Elisabeth Erlacher-Vindel, Glen Gifford, Juan Lubroth, Mario Raviglione, Paula Fujiwara
Journal: The Lancet Infectious Diseases (2018)
Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair–Deficient/Microsatellite Instability–High Metastatic Colorectal Cancer
Authors: Michael J. Overman, Sara Lonardi, Ka Yeung Mark Wong, Heinz-Josef Lenz, Fabio Gelsomino, Massimo Aglietta, Michael A. Morse, Eric Van Cutsem, Ray McDermott, Andrew Hill, Michael B. Sawyer, Alain Hendlisz, Bart Neyns, Magali Svrcek, Rebecca A. Moss, Jean-Marie Ledeine, Z. Alexander Cao, Shital Kamble, Scott Kopetz, Thierry André
Journal: Journal of Clinical Oncology (2018)

Purpose Nivolumab provides clinical benefit (objective response rate [ORR], 31%; 95% CI, 20.8 to 42.9; disease control rate, 69%; 12-month overall survival [OS], 73%) in previously treated patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC); nivolumab plus ipilimumab may improve these outcomes. Efficacy and safety results for the nivolumab plus ipilimumab cohort of CheckMate-142, the largest single-study report of an immunotherapy combination in dMMR/MSI-H mCRC, are reported. Patients and Methods Patients received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks. Primary end point was investigator-assessed ORR. Results Of 119 patients, 76% had received ≥ two prior systemic therapies. At median follow-up of 13.4 months, investigator-assessed ORR was 55% (95% CI, 45.2 to 63.8), and disease control rate for ≥ 12 weeks was 80%. Median duration of response was not reached; most responses (94%) were ongoing at data cutoff. Progression-free survival rates were 76% (9 months) and 71% (12 months); respective OS rates were 87% and 85%. Statistically significant and clinically meaningful improvements were observed in patient-reported outcomes, including functioning, symptoms, and quality of life. Grade 3 to 4 treatment-related adverse events (AEs) occurred in 32% of patients and were manageable. Patients (13%) who discontinued treatment because of study drug-related AEs had an ORR (63%) consistent with that of the overall population. Conclusion Nivolumab plus ipilimumab demonstrated high response rates, encouraging progression-free survival and OS at 12 months, manageable safety, and meaningful improvements in key patient-reported outcomes. Indirect comparisons suggest combination therapy provides improved efficacy relative to anti-programmed death-1 monotherapy and has a favorable benefit-risk profile. Nivolumab plus ipilimumab provides a promising new treatment option for patients with dMMR/MSI-H mCRC.
Bone Marrow Levels of PARP1 mRNA Predict Response to Treatment with 5-Azacytidine in Patients with Myelodysplastic Syndrome
Authors: Panagiotis Theodorou Diamantopoulos, Elina Kodandreopoulou, Argiris S. Symeonidis, Ioannis Kotsianidis, Vassiliki Pappa, Athanasios Galanopoulos, Maria Dimou, Georgia Christopoulou, Konstantinos Zervakis, Elena E. Solomou, Marie-Christine Kyrtsonis, Niki Rougala, Marina Siakantaris, Theodoros Vassilakopoulos, Panayiotis Panayiotidis, Nora-Athina Viniou
Journal: Blood (2017)
Resistance Is Futile: Engineering the Adoptive T-Cell Therapies of the Future
Authors: Eugene Shenderov, Richard F. Ambinder
Journal: Journal of Clinical Oncology (2018)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Tumor-Specific T-Cells Engineered to Overcome Tumor Immune Evasion Induce Clinical Responses in Patients With Relapsed Hodgkin Lymphoma. January 09, 2018 ARTICLE CITATION DOI: 10.1200/JCO.2017.76.6618 Journal of Clinical Oncology - published online before print January 24, 2018 PMID: 29364774 Resistance Is Futile: Engineering the Adoptive T-Cell Therapies of the Future Eugene ShenderovxEugene ShenderovSearch for articles by this author and Richard F. AmbinderxRichard F. AmbinderSearch for articles by this author Show More Eugene Shenderov and Richard F. Ambinder, Johns Hopkins School of Medicine, Baltimore, MD https://doi.org/10.1200/JCO.2017.76.6618 First Page Full Text PDF Figures and Tables © 2018 by American Society of Clinical Oncology Companion Tumor-Specific T-Cells Engineered to Overcome Tumor Immune Evasion Induce Clinical Responses in Patients With Relapsed Hodgkin Lymphoma
Management of chronic hepatitis B patients in immunetolerant phase: what latest guidelines recommend
Authors: Grace Lai-Hung Wong
Journal: Clinical and Molecular Hepatology (2018)

The natural history of chronic hepatitis B (CHB) is complex and may run through different immune phases that may overlap. In particulars, the immune-tolerant phase is the most interesting and not as well understood as we thought. The concept of true immune tolerance have been under challenged from immunology points of view. The major international guidelines have not yet reached a consensus on the definition of the immune-tolerant phase. While positive hepatitis B e antigen (HBeAg), high serum hepatitis B virus (HBV) DNA and normal serum alanine aminotransferase (ALT) levels are the three key features of this phase, some guidelines also put age into consideration. A new nomenclature, Phase 1 or HBeAg-positive chronic HBV infection, is given by the latest European Association for the Study of the Liver (EASL) published in April 2017. While current guidelines advise against starting antiviral treatment for immune-tolerant CHB patients, some new data suggest treating such patients may reduce the risk of liver fibrosis progression and hepatocellular carcinoma. Keywords: Chronic hepatitis B; Hepatocellular carcinoma; Immune tolerance; Liver fibrosis; Positive HBeAg
Abstract 20023: ApoA-I Mimetic Peptide 4F Inhibits Inflammatory Bowel Disease in Mice
Authors: David Meriwether, Carmen Volpe, Victor Grijalva, Pallavi Mukherjee, Martin Martin, G.M. Anantharamaiah, Alan M Fogelman, Srinivasa T Reddy
Journal: Circulation (2016)

Introduction:  Inflammatory bowel disease (IBD) has been linked to an increased prevalence of early stage vascular disease. The apoA-I mimetic peptide 4F is a potential therapeutic agent for the treatment of inflammatory diseases including atherosclerosis. The mechanism of action of 4F is localized to the small intestine, where we have shown that 4F can alter lipid signaling and regulate cholesterol efflux.   Hypothesis:  Given the mechanism of action, we hypothesized that 4F might protect against the development of IBD. We previously reported that COX-2 deficient mice develop Crohn’s-like disease when fed a cholate diet. We thus examined whether 4F treatment alters the development of Crohn’s-like inflammation in this IBD model.   Methods:  Myeloid COX-2 deficient mice were challenged with a cholate-containing diet while being treated with 4F. After 7 and 10 weeks, the surviving mice were sacrificed and analyzed for intestinal inflammation in the ileo-ceco-colic junction by gross histology and immunohistochemistry (IHC). Total cecal RNA was analyzed for inflammatory cytokines.   Results:  Only 57% (8/14) of control mice, but all 4F-treated mice (14/14) survived. 4F significantly reduced by 50% the thickness of the ileo-ceco-colic junctions while reducing muscularis thickness 5-fold. By 7 weeks, 4F treatment significantly inhibited TNFα while significantly increasing IL-10. 4F also significantly reduced the number of infiltrating macrophages (F4/80) and neutrophils (Ly6G) by 3 and 5-fold as measured by IHC.   Conclusions:  4F treatment largely abrogated measures of IBD in a COX2-deficient mouse model of Crohn’s disease.
PET/CT Guided Biopsy for the Diagnosis of Lymphoma
Authors: Alessandro Broccoli, Cristina Nanni, Alberta Cappelli, Francesco Bacci, Alessandro Gasbarrini, Lucia Zanoni, Stefano Brocchi, Sebastiano Spagnolo, Carlo Piovani, Lisa Argnani, Stefano Boriani, Elena Sabattini, Rita Golfieri, Stefano Fanti, Pier Luigi Zinzani
Journal: Blood (2017)
Combined antitumor effects of novel tubulin-polymerization inhibitor with some existing antitumor agents; capecitabine, irinotecan, cisplatin, trastuzumab and pertuzumab
Authors: Toshikazu Yamazaki, Toshiyuki Tsukaguchi, Fumie Sawamura, Tsutomu Takahashi, Masanori Miwa, Hiromi Tanimura, Naohito Inagaki, Takehiro Okada, Fumio Watanabe, Mary Simcox, Claude Gimmi, Kazuko Kobayashi, Nobuo Shimma, Mikio Arisawa, Yuko Aoki
Journal: Cancer Research (2007)

1440   Tubulin is a clinically validated target for anti-cancer therapy. Taxanes (microtubule stabilizers) are amongst the most powerful chemotherapeutic agents in NSCLC, breast cancer, ovarian cancer and prostate cancer. However, the clinical benefit obtained with these drugs has been limited by drug resistance acquired by tumors and the safety profile. Mechanisms of resistance to taxanes include mutations in the tubulin genes and overexpression of transmembrane drug efflux pumps (e.g. MDR1 and BCRP). Adverse events associated with taxanes include hematological toxicity, neurotoxicity and hypersensitivity reactions. For patients who acquire resistance to, or who failed prior treatment with taxanes, the success of salvage chemotherapy has been reported to be modest. Therefore, there is a need to develop new drugs targeting tubulin structure with better safety profile and less resistance.  We previously presented the potent antitumor activity of our synthetic dolastatin analogue (Compound 1) in a broad range of human xenograft models of NSCLC, breast cancer, colorectal cancer, prostate cancer and hepatocellular cancers including a taxane resistant tumor cell line. In our studies, we examined the antitumor activity of the combination of Compound 1 plus existing antitumor agents such as capecitabine, irinotecan, cisplatin, trastuzumab and pertuzumab in several human cancer xenograft models compared to single agent activity. Compound 1 exhibited synergistic/additive antitumor effects in combination with irinotecan (CPT-11) or with cisplatin (CDDP) in NSCLC models, with capecitabine in CRC models and with trastuzumab or pertuzumab in a Her2 positive breast cancer model. Tumor growth inhibition (TGI) in these combinations was statistically significant compared to those in single agent administration. Notably, the combination of Compound 1 with trastuzumab resulted in a high antitumor efficacy and also showed complete regression in some animals.  Thus, this new tubulin polymerization inhibitor not only shows significantly improved TGI as single agent compared to other tubulin interacting drugs on the market, but also in combination with existing antitumor drugs including molecular targeting agents. Based on this favorable pre-clinical profile, clinical studies are ongoing.
Prognostic histological factors in resected colorectal liver metastasis with preoperative treatment
Authors: Paméla Baldin, Marc Van den Eynde, Bernhard Mlecnik, Gabriela Bindea, Gabiela Beniuga, Javier Carrasco, Catherine Hubert, Benoît Navez, Géraldine Pairet, Anne Mourin, Jerome Galon, Mina Komuta
Journal: Hepatology (2017)
Impact of Number of Prior Therapies and Bulk of Disease on Outcomes with Venetoclax (VEN) Monotherapy for Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)
Authors: William G Wierda, John F Seymour, Andrew W. Roberts, Su Young Kim, L. Leanne Lash-Fleming, Johnathan Maher, Todd Busman, Lang Zhou, Jacqueline Nielsen, Stephan Stilgenbauer
Journal: Blood (2017)
Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation
Authors: Eileen Goodwin, Morgan S.A. Gilman, Daniel Wrapp, Man Chen, Joan O. Ngwuta, Syed M. Moin, Patricia Bai, Arvind Sivasubramanian, Ruth I. Connor, Peter F. Wright, Barney S. Graham, Jason S. McLellan, Laura M. Walker
Journal: Immunity (2018)
Editorial Evaluation, Peer Review, and Publication of Research Reports With and Without Supplementary Online Content
Authors: Annette Flanagin, Stacy L. Christiansen, Chris Borden, Demetrios N. Kyriacou, Caroline Sietmann, Elaine Williams, Larry Bryant
Journal: JAMA (2018)

This study assesses whether research manuscripts with supplemental material submitted in 2016 to JAMA, JAMA Internal Medicine, and JAMA Pediatrics were more likely than those without supplements to undergo peer review, be accepted, and have more online views and downloads.
Role of Preoperative Variables in Reducing the Rate of Occult Invasive Disease for Women Considering Active Surveillance for Ductal Carcinoma In Situ—Reply
Authors: Sharon S. Lum, Carlos Chavez de Paz Villanueva
Journal: JAMA Surgery (2018)

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Abstract 18173: Western Type Dietary Pattern is Associated With the Severity and Extent of Coronary Artery Disease
Authors: Georgios Georgiopoulos, Evangelos Oikonomou, Gerasimos Siasos, Eleni Kokkou, Alexios S Antonopoulos, Georgia Vogiatzi, Konstantinos Mourouzis, George-Angelo Papamikroulis, Angelos Papanikolaou, Sotirios Tsalamandris, Dimitrios Tousoulis
Journal: Circulation (2017)

Introduction: The impact of diet on atherosclerosis progression is well established although, the independent predictive value of unhealthy diet in the prognosis and severity of CAD has not been in...
Localized Myosin II Activity Regulates Assembly and Plasticity of the Axon Initial Segment
Authors: Stephen L. Berger, Alejandra Leo-Macias, Stephanie Yuen, Latika Khatri, Sylvia Pfennig, Yanqing Zhang, Esperanza Agullo-Pascual, Ghislaine Caillol, Min-Sheng Zhu, Eli Rothenberg, Carmen V. Melendez-Vasquez, Mario Delmar, Christophe Leterrier, James L. Salzer
Journal: Neuron (2018)
Hypersensitivity To Nonsteroidal Antiinflammatories: Immediate Selective Reactions to Arylpropionic Acids In A Population In Madrid
Authors: Marcos Sanchez-Dominguez, Ana Rodriguez-Fernandez, Ines Torrado, Blanca Noguerado-Mellado, Patricia Rojas-Perez-Ezquerra
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 18503: Relationship Between Left Ventricular Fibrosis and Abnormalities of Mitral Annulus in Arrhythmic Mitral Valve Prolapse
Authors: Martina Perazzolo Marra, Cristina Basso, Manuel De Lazzari, Stefania Rizzo, Alberto Cipriani, Benedetta Giorgi, Carmelo Lacognata, Ilaria Rigato, Federico Migliore, Kalliopi Pilichou, Luisa Cacciavillani, Emanuele Bertaglia, Anna Chiara Frigo, Barbara Bauce, Domenico Corrado, Gaetano Thiene, Sabino Iliceto
Journal: Circulation (2016)

Introduction:  Mitral valve prolapse (MVP) is characterized by myxomatous leaflets and in those subjects with malignant ventricular arrhythmias the presence of myocardial fibrosis at the level left ventricular inferobasal wall and papillary muscles have been recently demonstrated.   Hypothesis:  We investigated the role of morpho-functional abnormalities of the mitral valve that could explain a regional mechanical myocardial stretch.   Methods and Results:  Thirty-seven (28 females; median age 43 years) arrhythmic MVP patients with LV late-gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) and no or trivial mitral regurgitation and 18 (7 females; median age 40 years) MVP patients without LGE were investigated by morpho-functional CMR. Mitral annulus disjunction (MAD, median 4.9 mm vs. 0.8, p 1.5 (23, 62%; vs. 4, 22% p=0.005) were higher in MVP patients with LGE than in those without. A Spearman’s correlation coefficient was found between MAD and curling (r=0.853, p   Conclusions:  In our study MAD seems a constant feature of arrhythmic MVP with LV fibrosis. These data could explain that the excessive mobility of the leaflets caused by posterior systolic curling may account for a mechanical stretch of the inferobasal wall and papillary muscles, eventually leading to myocardial hypertrophy and scarring. These mitral annulus abnormalities, together with auscultatory mid-systolic click, may identify MVP patients who would need arrhythmic risk stratification.
Reclassifying Acute Respiratory Distress Syndrome
Authors: Giorgia Maiolo, Francesca Collino, Francesco Vasques, Francesca Rapetti, Tommaso Tonetti, Federica Romitti, Massimo Cressoni, Davide Chiumello, Onnen Moerer, Peter Herrmann, Tim Friede, Michael Quintel, Luciano Gattinoni
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

The ratio of PaO2 to FiO2 (P/F) defines acute respiratory distress syndrome (ARDS) severity and suggests appropriate therapies.We investigated 1) whether a 150-mm-Hg P/F threshold within the range of moderate ARDS (100-200 mm Hg) would define two subgroups that were more homogeneous; and 2) which criteria led the clinicians to apply extracorporeal membrane oxygenation (ECMO) in severe ARDS.At the 150-mm-Hg P/F threshold, moderate patients were split into mild-moderate (n = 50) and moderate-severe (n = 55) groups. Patients with severe ARDS (FiO2 not available in three patients) were split into higher (n = 63) and lower (n = 18) FiO2 groups at an 80% FiO2 threshold.Compared with mild-moderate ARDS, patients with moderate-severe ARDS had higher peak pressures, PaCO2, and pH. They also had heavier lungs, greater inhomogeneity, more noninflated tissue, and greater lung recruitability. Within 84 patients with severe ARDS (P/F < 100 mm Hg), 75% belonged to the higher FiO2 subgroup. They differed from the patients with severe ARDS with lower FiO2 only in PaCO2 and lung weight. Forty-one of 46 patients treated with ECMO belonged to the higher FiO2 group. Within this group, the patients receiving ECMO had higher PaCO2 than the 22 non-ECMO patients. The inhomogeneity ratio, total lung weight, and noninflated tissue were also significantly higher.Using the 150-mm-Hg P/F threshold gave a more homogeneous distribution of patients with ARDS across the severity subgroups and identified two populations that differed in their anatomical and physiological characteristics. The patients treated with ECMO belonged to the severe ARDS group, and almost 90% of them belonged to the higher FiO2 subgroup.
Abstract 17567: Bicuspid Aortic Valve Disease: Anatomical Characteristics and Stent Frame Geometry Following Sapien 3 Transcatheter Aortic Valve Implantation
Authors: Hiroyuki Kawamori, Yigal Abramowitz, Tarun Chakravarty, Yoshio Maeno, Yoshio Kazuno, Nobuyuki Takahashi, Mohammad Kashif, Geeteshwar Mangat, Wen Cheng, Raj R. Makkar, Hasan Jilaihawi
Journal: Circulation (2016)

Introduction: Patients with Bicuspid aortic valve (BAV) disease have been excluded from clinical trial because of anatomical variations and safety considerations. Hypothesis: Patients with BAV that...
Identification of Candidate Progenitor Populations Which Causes Transient Abnormal Myelopoiesis
Authors: Yoko Nishinaka-Arai, Akira Niwa, Shiori Matsuo, Yasuhiro Kazuki, Yuwna Yakura, Mitsuo Oshimura, Tatsutoshi Nakahata, Megumu K Saito
Journal: Blood (2017)
Global nephrology workforce: gaps and opportunities toward a sustainable kidney care system
Authors: Mohamed A. Osman, Mona Alrukhaimi, Gloria E. Ashuntantang, Ezequiel Bellorin-Font, Mohammed Benghanem Gharbi, Branko Braam, Mark Courtney, John Feehally, David C. Harris, Vivekanand Jha, Kailash Jindal, David W. Johnson, Kamyar Kalantar-Zadeh, Rumeyza Kazancioglu, Scott Klarenbach, Adeera Levin, Meaghan Lunney, Ikechi G. Okpechi, Timothy Olusegun Olanrewaju, Jeffrey Perl, Harun Ur Rashid, Eric Rondeau, Babatunde Lawal Salako, Arian Samimi, Laura Sola, Irma Tchokhonelidze, Natasha Wiebe, Chih-Wei Yang, Feng Ye, Alexander Zemchenkov, Ming-hui Zhao, Aminu K. Bello
Journal: Kidney International Supplements (2018)
Effective and Ineffective Samples of Mesenchymal Multipotent Stromal Cells Used for Acute Graft-Versus-Host Disease Prophylaxis after Allogeneic Bone Marrow Transplantation Differ in the Expression Level of HLA-DR When Co-Cultured with Activated Lymphocytes
Authors: Nataliya Petinati, Nikolay M. Kapranov, Yuliya O Davydova, Alexey Bigildeev, Natalia Sats, Irina Shipounova, Nina Drize, Irina V. Galtseva, Larisa A. Kuzmina, Elena N. Parovichnikova, Valeriy G. Savchenko
Journal: Blood (2017)
Abstract 13139: Fasting Triglycerides Are Independently Associated With Subclinical Atherosclerosis: The ELSA-Brasil Study
Authors: Marcio S Bittencourt, Raul D Santos, Henrique Staniak, Itamar S Santos, Alexandre C Pereira, Sreenivasa R Seshasai, Antonio Vallejo-Vaz, Kausik Ray, Bruce B Duncan, Isabela M Bensenor, Paulo Lotufo
Journal: Circulation (2015)

Introduction: While triglycerides (TG) are associated with cardiovascular disease, most studies suggests that non-fasting TG drives this effect, whereas the role of fasting TG is less well established. Hypothesis: We have evaluated whether triglyceride-derived markers (log-transformed TG [lnTG], non-HDL, TG/HDL ratio) and HDL independently predict subclinical coronary artery disease as measured by the coronary artery calcium score (CAC). Methods: We included 2911 (50.3±8.5 years, 54% women) participants from the ELSA-Brasil study who had no prior history of CVD, were not currently using lipid-lowering medications and underwent CAC evaluation. We analyzed the independent association of triglyceride-derived markers (lnTG, non-HDL, TG/HDL ratio) and HDL with CAC using logistic regression. Results: Among the 2911 participants, 759 (26%) had a CAC &gt;0, and 247 (8.5%) had a CAC &gt; 100. The median triglycerides level was 112 (IQR: 80 -162). Individuals with CAC&gt;0 had higher TG levels than those with CAC=0 (p&lt;0.001). They also had higher levels of total cholesterol, LDL, non-HDL levels, lower HDL and higher TG/HDL ratios (all p&lt;0.001). After adjustment for clinical risk factors log transformed TG, non-HDL and TG/HDL ratio remained significantly associated with CAC (allp&lt;0.05), while HDL did not. Even after further adjustment for body mass-index (BMI) and for high sensitivity CRP, those predictors remained independently associated with CAC (table). Conclusions: In a large cohort of asymptomatic individuals, measures associated with fasting TG were associated with CAC score. Even after adjustment for clinical risk factors, BMI and hsCRP, measures associated with TG (lnTG, non-HDL and TG/HDL ratio) all remained independent predictors of CAC, while HDL did not. This suggests that TG may potentially be an independent target for therapy to reduce residual cardiovascular risk.