tbuckley/cabot-search huggingface dataset:
Calciphylaxis in haemodialysed patients: diagnostic value of calcifications in cutaneous biopsy
Authors: C. Cassius, P. Moguelet, J.B. Monfort, H. Fessi, P.A. Michel, G. Boulahia, K. Cury, C. Frances, P. Senet
Journal: British Journal of Dermatology (2017)

Calciphylaxis or calcific uremia arteriopathy (CUA) is a rare and highly morbid condition that predominantly affects dialyzed end-stage renal disease (ESRD) patients1. One-year survival rate is estimated to be 40-50%, with sepsis emerging as the leading cause of death 2. Calciphylaxis presents with painful necrotic cutaneous ulcers, livedo racemosa, hemorrhagic patches, indurated plaques, or hemorrhagic bullae predominantly on the proximal lower extremities and trunk 2.

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Treatment with selonsertib, an inhibitor of apoptosis signal-regulating kinase 1, hepatic phospho-p38 expression and markers of hepatocellular apoptosis and necrosis in patients with nonalcoholic steatohepatitis
Authors: A.M. Diehl, D. French, R. Xu, R. Loomba, E. Lawitz, B. Freilich, M.L. Shiffman, N. Chalasani, B. Hameed, S. Caldwell, M. Rinella, M. Peach, E. Huntzicker, S. Turner, T. Sullivan, G. Chen, C.S. Djedjos, R.P. Myers, G.M. Subramanian, Z. Goodman, C. Sirlin, M. Charlton, N.H. Afdhal
Journal: Journal of Hepatology (2017)
Noninvasive Interrogation of DLL3 Expression in Metastatic Small Cell Lung Cancer
Authors: Sai Kiran Sharma, Jacob Pourat, Dalya Abdel-Atti, Sean D. Carlin, Alessandra Piersigilli, Alexander J. Bankovich, Eric E. Gardner, Omar Hamdy, Kumiko Isse, Sheila Bheddah, Joseph Sandoval, Kristen M. Cunanan, Eric B. Johansen, Viola Allaj, Vikram Sisodiya, David Liu, Brian M. Zeglis, Charles M. Rudin, Scott J. Dylla, John T. Poirier, Jason S. Lewis
Journal: Cancer Research (2017)

Abstract The Notch ligand DLL3 has emerged as a novel therapeutic target expressed in small cell lung cancer (SCLC) and high-grade neuroendocrine carcinomas. Rovalpituzumab teserine (Rova-T; SC16LD6.5) is a first-in-class DLL3-targeted antibody–drug conjugate with encouraging initial safety and efficacy profiles in SCLC in the clinic. Here we demonstrate that tumor expression of DLL3, although orders of magnitude lower in surface protein expression than typical oncology targets of immunoPET, can serve as an imaging biomarker for SCLC. We developed 89Zr-labeled SC16 antibody as a companion diagnostic agent to facilitate selection of patients for treatment with Rova-T based on a noninvasive interrogation of the in vivo status of DLL3 expression using PET imaging. Despite low cell-surface abundance of DLL3, immunoPET imaging with 89Zr-labeled SC16 antibody enabled delineation of subcutaneous and orthotopic SCLC tumor xenografts as well as distant organ metastases with high sensitivity. Uptake of the radiotracer in tumors was concordant with levels of DLL3 expression and, most notably, DLL3 immunoPET yielded rank-order correlation for response to SC16LD6.5 therapy in SCLC patient–derived xenograft models. Cancer Res; 77(14); 3931–41. ©2017 AACR.
IL-4 and IL13 promote liver fibrosis signaling through M2 macrophages, but not Th2 T cells or hepatocytes
Authors: S.-Y. Weng, X. Wang, S. Vijayan, Y.O. Kim, L. Kaps, Y. Tang, O. Molokanova, J. Crosby, M. Mccaleb, F. Brombacher, A. Waisman, E. Bockamp, D. Schuppan
Journal: Journal of Hepatology (2017)
Fecal microbiota transplant using a precision medicine approach is safe, Associated with lower hospitalization risk and improved cognitive function in recurrent hepatic encephalopathy
Authors: J.S. Bajaj, Z. Kassam, A. Fagan, E.A. Gavis, E. Liu, J. Cox, R. Kheradman, D. Heuman, J. Wang, T. Gurry, R. Williams, M. Sikaroodi, M. Fuchs, E. Alm, B. John, B. Arrowsmith, A. Riva, M. Smith, S.D. Taylor-Robinson, P. Gillevet
Journal: Journal of Hepatology (2017)
Abstract 70: mTOR Is Essential for Normal Heart Development and Compensatory Cardiac Growth in Fetal Mice
Authors: Maria Hennig, Manuela Magarin, Kom Voy Yin, Mary Jane Black, Ludwig Thierfelder, Jörg-Detlef Drenckhahn
Journal: Circulation Research (2012)

Remarkable growth plasticity enables the prenatal mammalian heart to counteract various unfavorable intrauterine conditions and build a functional and normally sized organ at birth. We have recently shown that the murine embryonic and fetal heart has a substantial regenerative capacity in response to tissue mosaicism for mitochondrial dysfunction caused by heart specific inactivation of the X-linked holocytochrome c synthase (Hccs) gene. In heterozygous Hccs knockout (Hccs+/-) embryos, hyperproliferation of healthy cardiomyocytes compensates for the functional loss of 50% cardiac cells, ensuring formation of a functional heart at birth. However, we hypothesized that embryonic heart regeneration alters peri- and postnatal cardiac growth mechanisms. Indeed, neonatal Hccs+/- hearts are hypoplastic containing a reduced number of cardiomyocytes, whereas in adult Hccs+/- hearts compensatory cellular hypertrophy normalizes morphology and size. We aimed at identifying postnatal adaptive growth mechanisms utilized by the hypoplastic Hccs+/- heart to restore organ size and allow normal heart function throughout lifetime. Microarray RNA expression analyses revealed numerous genes involved in amino acid metabolism, protein homeostasis and translational control being differentially expressed in neonatal Hccs+/- hearts. Subsequently, western blot analyses evidenced significantly increased mammalian target of rapamycin (mTOR) activity, a major regulator of translation and cell growth, in Hccs+/- hearts compared to controls. To clarify its role for compensatory growth of the Hccs+/- myocardium, we inhibited mTOR in fetal and neonatal mice by rapamycin treatment of pregnant dams. Rapamycin treated Hccs+/- neonates (n=17) show significantly reduced heart weight to body weight ratios compared to controls (n=18) or vehicle treated animals (n=12 and n=13). Furthermore, Hccs+/- hearts after prenatal mTOR inhibition are morphologically characterized by developmental delay. In conclusion, our data revealed mTOR being essential for normal as well as compensatory growth of the fetal heart. Thus, metabolic adaptations converging on mTOR might be required to prevent postnatal heart disease after impaired intrauterine development.
Monitoring influenza virus susceptibility to oseltamivir using a new rapid assay, iART
Authors: Larisa V Gubareva, Eric Fallows, Vasiliy P Mishin, Erin Hodges, Abdullah Brooks, John Barnes, Alicia M Fry, William Kramp, Roxanne Shively, David E Wentworth, Kristin Weidemaier, Ross Jacobson
Journal: Eurosurveillance (2017)

A new rapid assay for detecting oseltamivir resistance in influenza virus, iART, was used to test 149 clinical specimens. Results were obtained for 132, with iART indicating 41 as 'resistant'. For these, sequence analysis found known and suspected markers of oseltamivir resistance, while no such markers were detected for the remaining 91 samples. Viruses isolated from the 41 specimens showed reduced or highly reduced inhibition by neuraminidase inhibition assay. iART may facilitate broader antiviral resistance testing.
Efficacy and safety of simtuzumab for the treatment of primary sclerosing cholangitis: results of a phase 2b, dose-ranging, randomized, placebo-controlled trial
Authors: A. Muir, Z. Goodman, C. Levy, H. Janssen, A. Montano-Loza, C. Bowlus, D. Ding, C. Jia, B. McColgan, R. Myers, M. Subramanian, J. McHutchison, M. Manns, R. Chapman, N. Afdhal, B. Eksteen
Journal: Journal of Hepatology (2017)
The Role of Variability in Motor Learning
Authors: Ashesh K. Dhawale, Maurice A. Smith, Bence P. Ölveczky
Journal: Annual Review of Neuroscience (2017)

Trial-to-trial variability in the execution of movements and motor skills is ubiquitous and widely considered to be the unwanted consequence of a noisy nervous system. However, recent studies have suggested that motor variability may also be a feature of how sensorimotor systems operate and learn. This view, rooted in reinforcement learning theory, equates motor variability with purposeful exploration of motor space that, when coupled with reinforcement, can drive motor learning. Here we review studies that explore the relationship between motor variability and motor learning in both humans and animal models. We discuss neural circuit mechanisms that underlie the generation and regulation of motor variability and consider the implications that this work has for our understanding of motor learning.
Alpha-fetoprotein levels before and after sustained virological response with direct- acting antivirals in patients with liver cirrhosis due to hepatitis C virus
Authors: C. Alvarez-Navascues, A. Castaño, M.A. de Jorge, C. Rodriguez-Escaja, E. Rubio, M. Varela, V. Cadahia, L. Gonzalez-Dieguez, M. Rodriguez
Journal: Journal of Hepatology (2017)
The first Americans
Authors: Steven H Woolf
Journal: BMJ (2003)

From BMJ USA 2003;May:234 

In an 1808 letter to Congress, Thomas Jefferson wrote, “With our Indian neighbors the public peace has been steadily maintained. Some instances of individual wrong have, as at other times, taken place, but in nowise implicating the will of the nation… And, generally, from a conviction that we consider them as part of ourselves, and cherish with sincerity their rights and interests, the attachment of the Indian tribes is gaining strength daily - is extending from the nearer to the more remote, and will amply requite us for the justice and friendship practised towards them” (http://memory.loc.gov/ammem/mtjhtml/mtjhome.html).

Now, 200 years later, …
Comprehensive genomic profiling of advanced stage esophageal squamous cell carcinomas (ESCC) and esophageal adenocarcinomas (EAC).
Authors: Adrienne Johnson, Siraj Mahamed Ali, Roman Yelensky, Juliann Chmielecki, Julia Andrea Elvin, Doron Lipson, Vincent A. Miller, Philip J. Stephens, Jeffrey S. Ross, Kai Wang
Journal: Journal of Clinical Oncology (2015)

1535 Background: Esophageal Squamous Cell Carcinomas (ESCC) and Esophageal Adenocarcinomas (EAC) account for > 95% of esophageal malignancies. Using a sensitive sequencing assay, we compared the genomic profiles of ESCC and EAC focused on the ability to identify potential targets for therapy in the 2 diseases. Methods: DNA was extracted from 40u of FFPE sections from 71 clinically advanced ESCC and 231 EAC. Next generation sequencing based comprehensive genomic profiling (NGS) was performed on hybridization-captured, adaptor ligation based libraries to a median coverage depth of > 650x for 236 cancer-related genes. The results were evaluated for all classes of genomic alterations (GA). Clinically relevant genomic alterations (CRGA) were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials. Results: There were no significant differences in the age range for ESCC and EAC (median: 63 vs. 60 years). All ESCC and EAC were at an advanced stage (Stage III/IV) at the time of sequencing. GA per sample on average in 71 ESCC and 231 EAC were 7.4 and 5.6 respectively. The frequency of CRGA in ESCC (2.6/sample; 94.4% of cases) and EAC (2.7/sample; 93.1% of cases) were similar. CRGA more frequently identified in ESCC than EAC included PIK3CA (24% vs 10%), PTEN (11% vs 4%), CCND1 (42% vs 13%) and NOTCH1 (17% vs 3%). CRGA more frequently altered in EAC than ESCC included KRAS (23% vs 6%) and ERBB2 (23% vs 3%). Other GA that were significantly different in the 2 tumor types included SMAD4 (1% ESCC vs 14% EAC), SOX2 (18% ESCC vs 1% EAC) and NFE2L2 (24% ESCC vs 1% EAC). EGFR was altered in 8% of ESCC and 15% of EAC. Clinical case examples of patient responses to targeted therapy will be presented. Conclusions: ESCC and EAC share common high frequencies of overall and clinically relevant GA. However, PI3K/mTOR (PIK3CA and PTEN) and Notch pathway genes were significantly enriched in ESCC, and RAS/MEK pathway genes (ERBB2 and KRAS) were significantly enriched in EAC. Comprehensive genomic profiling shows significant promise to identify CRGA in both ESCC and EAC and lead to potential use of clinical outcome altering targeted therapies in both major types of esophageal cancer.
Impact of “rescue allocated” livers on outcomes after liver transplantation: a propensity score matching analysis
Authors: M. Disabato, C.G. Gavara, A. Winter, H. Hentati, C. Lim, C. Salloum, E. Levesque, C. Feray, D. Azoulay, P. Compagnon
Journal: Journal of Hepatology (2017)
Significance of serum exosomal miR-122 and miR-21 as a predictive biomarker in hepatocellular carcinoma patients who underwent transarterial chemoembolization
Authors: T. Suehiro, H. Miyaaki, H. Shibata, T. Honda, E. Ozawa, S. Miuma, N. Taura, K. Nakao
Journal: Journal of Hepatology (2017)
The Ileal Bile Acid Transport inhibitor A4250 decreases pruritus and serum bile acids in cholestatic liver diseases – an ongoing multiple dose, open-label, multicentre study
Authors: U. Baumann, F. Lacaille, E. Sturm, E. Gonzalès, H. Arnell, M.H. Jørgensen, R.J. Thompson, M. Ekelund, J.P. Mattsson, E. Lindström, P.-G. Gillberg, K. Torfgård, P.N. Soni
Journal: Journal of Hepatology (2017)
High-risk behaviour in a cohort of HIV/hepatitis C coinfected gay and bisexual men commencing hepatitis C treatment
Authors: A.L. Bowing, J.S. Doyle, D.M. Iser, J. Sasadeusz, J. Roney, M. O’Reilly, C. Fairley, E. Gane, J. Hoy, G.V. Matthews, N. Medland, R. Moore, M. Prins, M. Stoové, T. Ban-Kiem, M.E. Hellard
Journal: Journal of Hepatology (2017)
Active versus passive follow-up examination of patients with chronic hepatitis C during Sofosbuvir/Ledipasvir treatment
Authors: G. Jargalsaikhan, B. Dashtseren, B. Dendev, M. Enkhbat, P. Bat-Ulzii, D. Boldbaatar, Z. Genden, D. Yagaanbuyant, A. Dagvadorj, A. Bungert, N. Dashdorj, N. Dashdorj
Journal: Journal of Hepatology (2017)
The effect of beta-hydroxy-beta-methyl butyrate supplementation on muscle wasting in patients undergoing liver transplantation: results of preliminary analysis
Authors: R. Lacetera, M. Giusto, B. Lattanzi, C. Albanese, V. Di Gregorio, D. D’Ambrosio, S.G. Corredini, G. Mennini, M. Rossi, M. Merli
Journal: Journal of Hepatology (2017)
Incidence of low grade non hodgkin lymphoma (real), in a captive population from Argentina
Authors: R. F. Bezares, F. Cueva, A. Arra, D. Martorelli, C. Baldornir, R. Gonzalez-Boix, H. Boubeta, A. Livio, C. A. Marin, L. Celebrin, D. Lafalce
Journal: Blood (2000)
Adipose tissue depots and inflammation: effects on plasticity and resident mesenchymal stem cell function
Authors: Lina Badimon, Judit Cubedo
Journal: Cardiovascular Research (2017)

Adipose tissue (AT) is a highly heterogeneous organ. Beside the heterogeneity associated to different tissue types (white, brown, and 'brite') and its location-related heterogeneity (subcutaneous, visceral, epicardial, and perivascular, etc.), AT composition, structure, and functionality are highly dependent on individual-associated factors. As such, the pro-inflammatory state associated to the presence of obesity and other cardiovascular risk factors (CVRFs) directly affects AT metabolism. Furthermore, the adipose-derived stem cells (ASCs) that reside in the stromal vascular fraction of AT, besides being responsible for most of the plasticity attributed to AT, is an additional source of heterogeneity. Thus, ASCs directly contribute to AT homeostasis, cell renewal, and spontaneous repair. These ASCs share many properties with the bone-marrow mesenchymal stem cells (i.e. potential to differentiate towards multiple tissue lineages, and angiogenic, antiapoptotic, and immunomodulatory properties). Moreover, ASCs show clear advantages in terms of accessibility and quantity of available sample, their easy in vitro expansion, and the possibility of having an autologous source. All these properties point out towards a potential use of ASCs in regenerative medicine. However, the presence of obesity and other CVRFs induces a pro-inflammatory state that directly impacts ASCs proliferation and differentiation capacities affecting their regenerative abilities. The focus of this review is to summarize how inflammation affects the different AT depots and the mechanisms by which these changes further enhance the obesity-associated metabolic disturbances. Furthermore, we highlight the impact of obesity-induced inflammation on ASCs properties and how those effects impair their plasticity.
Expression of CXCR7, CXCR4, CXCR3 and their chemokine ligands in glioblastoma.
Authors: Robert D. Berahovich, Matthew J. Walters, Timothy J. Sullivan, Holbrook Edwin Kohrt, Jason Karamchandani, Juan C. Jaen, Thomas J. Schall
Journal: Journal of Clinical Oncology (2012)

2043 Background: The chemokine receptors CXCR4 and CXCR7, and their shared ligand CXCL12/SDF-1, have been implicated in multiple aspects of tumorigenesis, including tumor cell proliferation, angiogenesis, vasculogenesis, and metastasis. Recently, a role for CXCR4 and CXCR7 has been postulated in the control of glioblastoma growth and vasculogenesis. We set out to define the expression patterns of these proteins on primary glioblastoma tumors and associated vasculature. Methods: First, a tumor microarray containing grades 1, 3, and 4 glioma samples were analyzed by immunohistochemical techniques for the expression of CXCR7. Second, two glioblastoma microarrays were analyzed by the same technique for CXCR7, CXCR4, and their shared chemokine ligand CXCL12. The same microarrays were also probed for the expression of the additional CXCR7 ligand, CXCL11/ITAC, as well as the chemokine receptor CXCR3, which is also a receptor for CXCL11. Tissues were scored in a blinded fashion by a certified neuropathologist for both the intensity of signal and location of signal for all proteins tested. Results: CXCR7 expression was largely dependent on tumor grade, as the receptor was usually absent on most grade 1 gliomas but was moderately-to-highly expressed in the majority of anaplastic astrocytomas and glioblastomas. CXCR7 expression on tumor-associated vasculature was seen in all samples and its expression level also increased with glioma grade. In contrast to CXCR7, CXCR4 expression in glioblastoma was usually limited to the glioma cells, with only infrequent expression on the vasculature. Conversely, CXCL12 expression in glioblastoma was usually limited to the vasculature. CXCR3 was detected in a subset of glioblastomas, and only on the glioma cells. The CXCR7 and CXCR3 ligand CXCL11 was, like CXCR7, expressed on both the glioma cells and vasculature. Conclusions: These results, in light of prior evidence for CXCR7 in tumor growth, suggest a positive role for CXCR7 in the development of glioblastoma. Because CXCR7 colocalizes with its ligands, CXCL12 and CXCL11, as well as their other receptors, CXCR4 and CXCR3, the function of CXCR7 in glioblastoma may lie in the regulation of both the CXCR4/CXCL12 and CXCR3/CXCL11 axes.
A critical role for the host mediator macrophage migration inhibitory factor in the pathogenesis of malarial anemia
Authors: Michael A. McDevitt, Jianlin Xie, Shanmugasundaram Ganapathy-Kanniappan, Jason Griffith, Aihua Liu, Courtney McDonald, Philip Thuma, Victor R. Gordeuk, Christine N. Metz, Robert Mitchell, Jeffrey Keefer, John David, Lin Leng, Richard Bucala
Journal: The Journal of Experimental Medicine (2015)
Proteasome dysfunction as a reversible defect underlying virus-specific CD8 cell exhaustion in chronic hepatitis B
Authors: P. Fisicaro, V. Barili, G. Acerbi, B. Montanini, D. Laccabue, F. Guerrieri, M. Massari, C. Vandelli, D. Salerno, G. Grossi, A. Alfieri, P. Lampertico, T. Giuberti, G. Missale, M. Levrero, S. Ottonello, C. Ferrari
Journal: Journal of Hepatology (2017)
THE USE OF NON-STEROIDAL ANTI-INFLAMMATORIES (NSAIDS) AT THE 2016 LONDON MARATHON
Authors: Steven Whatmough, Stephen Mears, Courtney Kipps
Journal: British Journal of Sports Medicine (2017)

Background Non-steroidal Anti-Inflammatories (NSAID) used during exercise are associated with medical risks. Such risks include gastric side effects and renal side effects (Kuster et al , 2013). More specifically NSAIDs are implicated in the development of exercise-associated hyponatremia (Hew-Butler et al , 2015)). Objective To identify the incidence of NSAID use in runners at the 2016 London Marathon. Design This study will take the form of a prospective observational study. Setting The 2016 London Marathon. Participants Participants were recruited during the marathon registration. 109 runners completed the questionnaire. In addition, a subset of 41 runners completed an immediate pre-race questionnaire on the morning of the race, of which 28 were followed up after crossing the finish line. Independent Variables Online and printed medical advice was available to all race participants. This included advice to refrain from using NSAIDs before and during the race was provided. Main Outcome Measures Planned NSAID use, actual NSAID use and awareness of safe doses and NSAID risks. Results 50 (45.9%) of the registration cohort planned to take an NSAID during the marathon. Of the athletes returning for data collection at the start line, 14 (34.1%) had already consumed an NSAID on the morning of the marathon. At the finish line, 16 of the 28 (57.1%) of athletes completing the study had consumed an NSAID. Seven runners had taken over the recommended dose of NSAID during the marathon. 13 (46%) correctly stated the risks of taking an NSAIDs, whilst only 10 (35%) were aware of the correct safe dose. Conclusions NSAID use by runners during the marathon remains high despite published medical guidance advising against its use. Overdose of NSAIDs is a concern as it carries increased risks. A lack of awareness of the risks of taking NSAIDs may contribute towards these findings.
Jnk2 is indispensable in murine and human Ibuprofen-induced acute liver failure
Authors: M.E. Zoubek, M.M. Woitok, S. Sydor, L.J. Nelson, L.P. Bechmann, M.I. Lucena, R.J. Andrade, A. Bast, G.H. Koek, C. Trautwein, F.J. Cubero
Journal: Journal of Hepatology (2017)
Proof of efficacy for Seladelpar, a selective PPAR-δ agonist, in patients with primary biliary cholangitis non-responsive to ursodeoxycholic acid: results of an international Phase 2 randomised controlled clinical study
Authors: G.M. Hirschfield, M.R. Galambos, C.L. Bowlus, M.G. Swain, Y. Doerffel, A.S. Steinberg, M. Varga, Y.-J. Choi, R.L. Martin, H. Chera, C.A. McWherter, P.F. Boudes, D. Jones
Journal: Journal of Hepatology (2017)