tbuckley/cabot-search huggingface dataset:
Divergence of Noncoding Regulatory Elements Explains Gene–Phenotype Differences between Human and Mouse Orthologous Genes
Authors: Seong Kyu Han, Donghyo Kim, Heetak Lee, Inhae Kim, Sanguk Kim
Journal: Molecular Biology and Evolution (2018)

Mice have been widely used as a model organism to investigate human gene–phenotype relationships based on a conjecture that orthologous genes generally perform similar functions and are associated with similar phenotypes. However, phenotypes associated with orthologous genes often turn out to be quite different between human and mouse. Herein, we devised a method to quantitatively compare phenotypes annotations associated with mouse models and human. Using semantic similarity comparisons, we identified orthologous genes with different phenotype annotations, of which the similarity score is on a par with that of random gene pairs. Analysis of sequence evolution and transcriptomic changes revealed that orthologous genes with phenotypic differences are correlated with changes in noncoding regulatory elements and tissue-specific expression profiles rather than changes in protein-coding sequences. To map accurate gene–phenotype relationships using model organisms, we propose that careful consideration of the evolutionary divergence of noncoding regulatory elements and transcriptomic profiles is essential.
Soluble Interleukin-6 (IL-6) Receptor With IL-6 Stimulates Megakaryopoiesis From Human CD34+ Cells Through Glycoprotein (gp)130 Signaling
Authors: Xingwei Sui, Kohichiro Tsuji, Yasuhiro Ebihara, Ryuhei Tanaka, Kenji Muraoka, Makoto Yoshida, Kaoru Yamada, Kiyoshi Yasukawa, Tetsuya Taga, Tadamitsu Kishimoto, Tatsutoshi Nakahata
Journal: Blood (1999)
Novel application of the matched case–control design to compare food supply chains during an Escherichia coli O157 outbreak, United Kingdom, 2016
Authors: Thomas Inns, Paul Cleary, Nick Bundle, Sarah Foulkes, Ashley Sharp, Lara Utsi, Chris McBrien, Rehman Teagle, Alison Waldram, Chris Williams, Cathy McCann, Rob Smith, Sepeedeh Saleh, Noel McCarthy, Roberto Vivancos, Jeremy Hawker, Valerie Decraene
Journal: Eurosurveillance (2018)

There is a need for innovative methods to investigate outbreaks of food-borne infection linked to produce with a complex distribution network. The investigation of a large outbreak of
Orthotopic liver transplantation of xenogeneic livers repopulated with autologous hepatocytes: proof of normal function and consistent survival
Authors: Stéphanie Lacotte, G. Oldani, A. Peloso, L.A. Orci, V. Delaune, S. Vijgen, L. Rubbia-Brandt, C. Toso
Journal: Journal of Hepatology (2018)
Einstein's Last Equation*
Authors: Bonnie Salomon
Journal: Annals of Internal Medicine (2018)

Ad Libitum17 April 2018Einstein's Last Equation*Bonnie Salomon, MDBonnie Salomon, MDDeerfield, Illinois (B.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M17-2994 Audio Reading - “Einstein's Last Equation*” Audio. Virginia L. Hood, MD, Annals Associate Editor, reads "Einstein's Last Equation*," by B. Salomon. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail I.Confounded by generalities, pages of equationsaside the bed, eye glasses, and a pen.Twelve pages in all, recipes for the voidexpanding like poured batter, his celestialpancake, or better, a strudel, sugaryribbons atop airy dough. What morecould a mortal want at this hour?To taste life, bite every morsel, great gulps,then disappear, traveling at the speed of lightbeyond the light, to where the light begins.II.Bodies in motion tend to stay in motionuntil great arteries surge in diameter, blowup like a child's balloon, Newtonian faithful.The law of Laplace fill them, at last,ready to float away.What ... Author, Article, and Disclosure InformationAffiliations: Deerfield, Illinois (B.S.)Current Author Address: Bonnie Salomon, MD; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “Einstein's Last Equation*” Audio. Virginia L. Hood, MD, Annals Associate Editor, reads "Einstein's Last Equation*," by B. Salomon. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 17 April 2018Volume 168, Issue 8Page: 599KeywordsAbdominal aortic aneurysmArteriesMortalityNursesTaste ePublished: 17 April 2018 Issue Published: 17 April 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Targeted thermal therapy with genetically engineered magnetite magnetosomes@RGD: Photothermia is far more efficient than magnetic hyperthermia
Authors: Anouchka Plan Sangnier, Sandra Preveral, Alberto Curcio, Amanda K. A. Silva, Chistopher T. Lefèvre, David Pignol, Yoann Lalatonne, Claire Wilhelm
Journal: Journal of Controlled Release (2018)
Chronic Hepatitis B Infection
Authors: Lydia S. Y. Tang, Emily Covert, Eleanor Wilson, Shyam Kottilil
Journal: JAMA (2018)

<h3>Importance</h3> More than 240 million individuals worldwide are infected with chronic hepatitis B virus (HBV). Among individuals with chronic HBV infection who are untreated, 15% to 40% progress to cirrhosis, which may lead to liver failure and liver cancer. <h3>Observations</h3> Pegylated interferon and nucleos(t)ide analogues (lamivudine, adefovir, entecavir, tenofovir disoproxil, and tenofovir alafenamide) suppress HBV DNA replication and improve liver inflammation and fibrosis. Long-term viral suppression is associated with regression of liver fibrosis and reduced risk of hepatocellular carcinoma in cohort studies. The cure (defined as hepatitis B surface antigen loss with undetectable HBV DNA) rates after treatment remain low (3%-7% with pegylated interferon and 1%-12% with nucleos[t]ide analogue therapy). Pegylated interferon therapy can be completed in 48 weeks and is not associated with the development of resistance; however, its use is limited by poor tolerability and adverse effects such as bone marrow suppression and exacerbation of existing neuropsychiatric symptoms such as depression. Newer agents (entecavir, tenofovir disoproxil, and tenofovir alafenamide) may be associated with a significantly reduced risk of drug resistance compared with older agents (lamivudine and adefovir) and should be considered as the first-line treatment. <h3>Conclusions and Relevance</h3> Antiviral treatment with either pegylated interferon or a nucleos(t)ide analogue (lamivudine, adefovir, entecavir, tenofovir disoproxil, or tenofovir alafenamide) should be offered to patients with chronic HBV infection and liver inflammation in an effort to reduce progression of liver disease. Nucleos(t)ide analogues should be considered as first-line therapy. Because cure rates are low, most patients will require therapy indefinitely.
A fibrin biofilm covers blood clots and protects from microbial invasion
Authors: Fraser L. Macrae, Cédric Duval, Praveen Papareddy, Stephen R. Baker, Nadira Yuldasheva, Katherine J. Kearney, Helen R. McPherson, Nathan Asquith, Joke Konings, Alessandro Casini, Jay L. Degen, Simon D. Connell, Helen Philippou, Alisa S. Wolberg, Heiko Herwald, Robert A.S. Ariëns
Journal: Journal of Clinical Investigation (2018)

Hemostasis requires conversion of fibrinogen to fibrin fibers that generate a characteristic network, interact with blood cells, and initiate tissue repair. The fibrin network is porous and highly permeable, but the spatial arrangement of the external clot face is unknown. Here we show that fibrin transitioned to the blood-air interface through Langmuir film formation, producing a protective film confining clots in human and mouse models. We demonstrated that only fibrin is required for formation of the film, and that it occurred in vitro and in vivo. The fibrin film connected to the underlying clot network through tethering fibers. It was digested by plasmin, and formation of the film was prevented with surfactants. Functionally, the film retained blood cells and protected against penetration by bacterial pathogens in a murine model of dermal infection. Our data show a remarkable aspect of blood clotting in which fibrin forms a protective film covering the external surface of the clot, defending the organism against microbial invasion.
P461Human pluripotent stem cell-derived endothelial cells are vasoactive in vitro and capable of engineering 3D vascular grafts
Authors: M Husveth-Toth, E Gara, A Nemes, A A Molnar, K Csepi, T Radovits, S E Harding, B Merkely, G Foldes
Journal: Cardiovascular Research (2018)

Human pluripotent stem cell-derived endothelial cells (hPSC-ECs) may be suitable for engineering three-dimensional vascular endothelial constructs.Here we studied the role and characteristics of 3D culture in vitro, in vivo and ex vivo on the arterial and venous fate of human embryonic and induced pluripotent stem cell-derived endothelial cells (hESC-EC and hiPSC-EC).We found that differentiated hPSC-EC could not only adhere to decellularised extracellular biomatrices but remained viable and functional during recellularization and underwent further maturation.The 3D culture of hiPSC-EC on acellular biomatrices increased expression of endothelial marker genes in vitro.In vivo conditioning of hPSC-EC in athymic nude rats also induced expression of arterial and venous endothelial marker genes.Levels of secreted angiogenesis (e.g.angiopoietins, endoglin, FGFs) and cell-matrix adhesion-related proteins (e.g.collagen XVIII, MMP8 and 9, TIMP1) were markedly higher when hiPSC-ECs were cultured on 3D vascular biomatrix compared to 2D cultures.Factors involved in the regulation of platelet aggregation or fibrinolytic pathway were also activated.Functional characterization of hESC-EC and hiPSC-EC revealed antiplatelet effects in engineered 3D vascular constructs and direct myogenic vasoactive effects in isolated vessel platform on aortic rings.In conclusion, the hPSC-ECs show mature endothelial characteristics and functional behaviour in 3D cultures.Our results improve understanding endothelial specification in 3D under in vitro and in vivo conditions may be critical in vascular tissue engineering.
Validation of AASLD treatment guideline eligibility based on disease outcomes of large community and clinical cohorts of chronic hepatitis B patients
Authors: D.H. Lee, A. Le, M. Chung, V.H. Nguyen, T. Johnson, F. Ji, E. Ogawa, H.N. Trinh, J. Zhang, C. Wong, C. Wong, J. Li, H.-I. Yang, M. Nguyen
Journal: Journal of Hepatology (2018)
Role of rare pathogenic mutations in the development of hepatocellular carcinoma in patients with nonalcoholic fatty liver disease
Authors: S. Pelusi, A. Pietrelli, G.A. Baselli, P. Dongiovanni, M. Meroni, B. Donati, A.L. Fracanzani, R. Romagnoli, S. Petta, L. Miele, A. Grieco, E. Bugianesi, G. Soardo, R. De Francesco, S. Fargion, L. Valenti
Journal: Journal of Hepatology (2018)
Trump administration could reject decades of landmark health studies under “transparency” rule
Authors: Owen Dyer
Journal: BMJ (2018)

The US Environmental Protection Agency (EPA) has unveiled a rule change that would only allow it to consider studies where the underlying data are made available publicly.

“The era of secret science at EPA is coming to an end,” said Scott Pruitt, administrator of the EPA, after signing the new rule. “Americans deserve to assess the legitimacy of the science underpinning decisions that may impact their lives.”

But scientists, former EPA staff, and public health groups said that this requirement would rule out the use of long standing, landmark studies that underpin much of the agency’s work, such as those linking leaded gasoline and pesticides to neurological damage and coal burning particulate pollution to premature deaths.

The seminal 1993 Harvard University “six cities” study that laid the ground for EPA regulation …
Heme Oxygenase-1 in Macrophages Drives Septic Cardiac Dysfunction via Suppressing Lysosomal Degradation of Inducible Nitric Oxide Synthase
Authors: Liangliang Jia, Yaping Wang, Yidong Wang, Yuankun Ma, Jian Shen, Zurong Fu, Yue Wu, Sheng’an Su, Yuhao Zhang, Zhejun Cai, Jian’an Wang, Meixiang Xiang
Journal: Circulation Research (2018)

To date, our understanding of the role of HO-1 (heme oxygenase-1) in inflammatory diseases has mostly been limited to its catalytic function and the potential for its heme-related catabolic products to suppress inflammation and oxidative stress. Whether and how HO-1 in macrophages plays a role in the development of septic cardiac dysfunction has never been explored.Here, we investigated the role of macrophage-derived HO-1 in septic cardiac dysfunction.Intraperitoneal injection of lipopolysaccharide significantly activated HO-1 expression in cardiac infiltrated macrophages. Surprisingly, we found that myeloid conditional HO-1 deletion in mice evoked resistance to lipopolysaccharide-triggered septic cardiac dysfunction and lethality in vivo, which was accompanied by reduced cardiomyocyte apoptosis in the septic hearts and decreased peroxynitrite production and iNOS (inducible NO synthase) in the cardiac infiltrated macrophages, whereas proinflammatory cytokine production and macrophage infiltration were unaltered. We further demonstrated that HO-1 suppression abolished the lipopolysaccharide-induced iNOS protein rather than mRNA expression in macrophages. Moreover, we confirmed that the inhibition of HO-1 promoted iNOS degradation through a lysosomal rather than proteasomal pathway in macrophages. Suppression of the lysosomal degradation of iNOS by bafilomycin A1 drove septic cardiac dysfunction in myeloid HO-1-deficient mice. Mechanistically, we demonstrated that HO-1 interacted with iNOS at the flavin mononucleotide domain, which further prevented iNOS conjugation with LC3 (light chain 3) and subsequent lysosomal degradation in macrophages. These effects were independent of HO-1's catabolic products: ferrous ion, carbon monoxide, and bilirubin.Our results indicate that HO-1 in macrophages drives septic cardiac dysfunction. The mechanistic insights provide potential therapeutic targets to treat septic cardiac dysfunction.
P496Remodeling of atrial action potential duration and atrial chamber deformation: a potential link in the development of atrial fibrillation?
Authors: L Sartiani, L Sartiani, M Cameli, L Dini, S Modillo, M Maccherini, B Le Grand, A Mugelli, E Cerbai
Journal: Cardiovascular Research (2018)

After an Acute Myocardial Infarction (AMI), Ischemia-Reperfusion (I/R) injury is responsible for a critical decrease in the number of viable cardiomyocytes (hCMs).Human myocardium harbors a population of endogenous cardiac stem/progenitor cells (hCSCs) that is activated upon I/R injury, contributing to myocardial repair through the establishment of an auto/paracrine molecular crosstalk between hCSCs and hCMs in stress.Clinical trials involving transplantation of hCSCs into the infarcted myocardium have demonstrated the potential of these cells.Although some improvements have been reported regarding increase in viable myocardium and improved tissue contractility, extensive data indicates that transplanted cells do not survive in the myocardium and this has led to the postulation of a paracrine mechanism for the observed beneficial effects.Using the same cells currently employed in the allogenous hCSCs transplantation clinical trial CARE-MI (EUDRA 2013-001358-81), our work aims at setting up an in vitro human I/R injury model using by using 3D culture approached combined with stirred tank bioreactor technology, in order to better decipher the mechanisms of action of hCSCs upon AMI using proteomic tools.By using aggregates of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) and a microcarreir based culture of hCSCs, injury setup was performed in bioreactors, allowing paracrine crosstalk between the two cell types via a reciprocal medium exchange via a perfusion system.Ischemia was mimicked by substituting growth media by Ischemia Mimetic Solution and placing the cells at 0% O2 for 5 hours.In the reperfusion step, cells were placed back in their physiological culture conditions (3% O2).The effect of I/R injury in hCSCs was accessed by quantitative total proteome analysis (using LC-MS) at different time points.Growth factor secretion, cells' viability, as well as hCSCs proliferation was also monitored in this co-culture system.Our first experiments in monolayer static systems showed that this model is able to recapitulate important features of I/R, including hCSC proliferation activation and a protective effect of hCSCs in hiPSC-CMs survival.Upon injury, proteome of hCSCs was enriched in proteins related to cell cycle regulation inhibition, proliferation through EGF signaling, gluthathione-mediated reactive oxygen species detoxification and paracrine signalling pathways.This system will allow further understanding on the molecular landscape of the myocardium during AMI, namely regarding hCSCs regenerative response and hCMs survival.The knowledge generated in this work will hopefully potentiate the development of novel molecular and cell-based therapies for myocardium regeneration.
NLRP6 Inflammasome-mediated intestinal dysbiosis drives steatohepatitis and promotes HCC progression
Authors: K. Schneider, A. Mohs, L.S. Candels, C. Elfers, L. Lijun, V. Bieghs, E. Latz, I. Bergheim, T. Strowig, C. Trautwein
Journal: Journal of Hepatology (2018)
Utility of FDG-PET/CT in pre-transplantation workup of the potential liver recipient with hepatocellular carcinoma
Authors: S.Y. Yi, J.H. Shim, G.W. Song, G.H. Choi, K.M. Kim, Y.-S. Lim, H.C. Lee, Y.-H. Chung, Y.S. Lee, S.-G. Lee
Journal: Journal of Hepatology (2018)
A hyper-glycosylation of HBV surface antigen characterizes immunosuppression-driven HBV reactivation and hinders HBsAg recognition in vitro
Authors: R. Salpini, L. Piermatteo, A. Battisti, L. Colagrossi, M. Aragri, L. Fabeni, A. Bertoli, C.M. Mastroianni, M. Marignani, S. Maylin, C. Delaugerre, F. Morisco, C. Nicola, A. Marrone, N. Iapadre, A. Mario, L. Sarmati, M. Andreoni, J. Verheyen, F.C. Silberstein, M. Levrero, C.F. Perno, L. Belloni, V. Svicher
Journal: Journal of Hepatology (2018)
RIP kinase 1–dependent endothelial necroptosis underlies systemic inflammatory response syndrome
Authors: Matija Zelic, Justine E. Roderick, Joanne A. O’Donnell, Jesse Lehman, Sung Eun Lim, Harish P. Janardhan, Chinmay M. Trivedi, Manolis Pasparakis, Michelle A. Kelliher
Journal: Journal of Clinical Investigation (2018)

Receptor interacting protein kinase 1 (RIPK1) has important kinase-dependent and kinase-independent scaffolding functions that activate or prevent apoptosis or necroptosis in a cell context–dependent manner. The kinase activity of RIPK1 mediates hypothermia and lethality in a mouse model of TNF-induced shock, reflecting the hyperinflammatory state of systemic inflammatory response syndrome (SIRS), where the proinflammatory "cytokine storm" has long been viewed as detrimental. Here, we demonstrate that cytokine and chemokine levels did not predict survival and, importantly, that kinase-inactive Ripk1D138N/D138N hematopoietic cells afforded little protection from TNF- or TNF/zVAD-induced shock in reconstituted mice. Unexpectedly, RIPK1 kinase–inactive mice transplanted with WT hematopoietic cells remained resistant to TNF-induced shock, revealing that a nonhematopoietic lineage mediated protection. TNF-treated Ripk1D138N/D138N mice exhibited no significant increases in intestinal or vascular permeability, nor did they activate the clotting cascade. We show that TNF administration damaged the liver vascular endothelium and induced phosphorylated mixed lineage kinase domain-like (phospho-MLKL) reactivity in endothelial cells isolated from TNF/zVAD-treated WT, but not Ripk1D138N/D138N, mice. These data reveal that the tissue damage present in this SIRS model is reflected, in part, by breaks in the vasculature due to endothelial cell necroptosis and thereby predict that RIPK1 kinase inhibitors may provide clinical benefit to shock and/or sepsis patients.
Previous Use of Antithrombotic Agents Reduces Mortality and Length of Hospital Stay in Patients With High-risk Upper Gastrointestinal Bleeding
Authors: Philip D.J. Dunne, Stig B. Laursen, Loren Laine, Harry R. Dalton, Jing H. Ngu, Michael Schultz, Adam Rahman, Andrea Anderloni, Iain A. Murray, Adrian J. Stanley
Journal: Clinical Gastroenterology and Hepatology (2018)
Impact of acute hepatic porphyrias on quality of life and work loss: An analysis of EXPLORE natural history study
Authors: L. Gouya, M. Balwani, D.M. Bissell, D. Rees, U. Stölzel, J. Phillips, R.K. Kauppinen, J.L. Langendonk, R. Desnick, J.C. Deybach, H. Bonkovsky, C. Parket, H. Naik, M. Badminton, P. Stein, E. Minder, J. Windyga, P. Martasek, M.D. Cappellini, P. Ventura, E. Sardh, P. Harper, S. Sandberg, A. Aarsand, F. Alegre, A. Ivanova, N. Talbi, A. Chan, K. Mccarthy, W. Querbes, C. Penz, S. Agarwal, A. Simon, K. Anderson
Journal: Journal of Hepatology (2018)
Viral Hepatitis in a Group of Boston Hospitals
Authors: George F. Grady, Thomas C. Chalmers
Journal: New England Journal of Medicine (1965)

SO much of the knowledge about viral hepatitis has come from studies of special populations such as young men in military service and mentally retarded children in institutions that it is appropriate to ask how different the disease may be when it occurs sporadically in the general population. Pooling of records from 9 Boston teaching hospitals cooperating with the Boston Inter-Hospital Liver Group provided an opportunity to study 1675 such patients. Some of them were hospitalized for diagnostic problems only, but most of the cases were representative of the more severe forms of hepatitis. A high mortality was anticipated but . . .
Clinical, paraclinical and MR-spectroscopy profile in cirrhotic and non-cirrhotic portal hypertension patients with minimal hepatic encephalopathy
Authors: B. Hermann, N. Weiss, M. Rudler, D. Galanaud, M. Mallet, C. Duvoux, A. Coilly, C. Francoz, A. Plessier, D. Thabut
Journal: Journal of Hepatology (2018)