tbuckley/cabot-search huggingface dataset:
Effect of antifibrotics on short-term outcome after bilateral lung transplantation: a multicentre analysis
Authors: Christopher Lambers, Panja M. Boehm, Silvia Lee, Fabio Ius, Peter Jaksch, Walter Klepetko, Igor Tudorache, Robin Ristl, Tobias Welte, Jens Gottlieb
Journal: European Respiratory Journal (2018)

Interstitial lung diseases (ILDs) are a heterogeneous entity of diffuse parenchymal lung diseases characterised by damage of the parenchyma as a result of varying patterns of inflammation and fibrosis [1]. Idiopathic pulmonary fibrosis (IPF) is a specific subgroup of ILDs and has a devastating prognosis [2] with a median survival time of 2–3 years [2–4]. Pirfenidone (Esbriet) and nintedanib (Ofev) were approved for IPF treatment, showing a stabilisation of the disease [5, 6], and are the treatments recommended by international guidelines [1]. Nintedanib was shown to increase the risk of bleeding events in IPF patients during therapy [7] and the European Medicines Agency recommended discontinuation of nintedanib before major surgery but without a definite time frame for discontinuation [8]. Corticosteroids have been the conventional strategy used as treatment in different ILD subtypes despite limited evidence regarding their efficacy [9, 10]. After failure of medical therapy in severe ILD, lung transplantation (LuTx) represents an established therapeutic option in order to improve quality of life and survival [11]. New antifibrotic therapies do not impair the clinical course or survival of patients with interstitial lung disease who underwent bilateral lung transplantation <http://ow.ly/7KoG30jyJmQ>
The Complexity and Heterogeneity of Monoclonal Immunoglobulin–Associated Renal Diseases
Authors: Sanjeev Sethi, S. Vincent Rajkumar, Vivette D. D’Agati
Journal: Journal of the American Society of Nephrology (2018)

Monoclonal gammopathies are characterized by the overproduction of monoclonal Ig (MIg) detectable in the serum or urine resulting from a clonal proliferation of plasma cells or B lymphocytes. The underlying hematologic conditions range from malignant neoplasms of plasma cells or B lymphocytes, including multiple myeloma and B-cell lymphoproliferative disorders, to nonmalignant small clonal proliferations. The term MGUS implies presence of an MIg in the setting of a "benign" hematologic condition without renal or other end organ damage. The term MGRS was recently introduced to indicate monoclonal gammopathy with MIg-associated renal disease in the absence of hematologic malignancy. Most MIg-associated renal diseases result from the direct deposition of nephrotoxic MIg or its light- or heavy-chain fragments in various renal tissue compartments. Immunofluorescence microscopy is essential to identify the offending MIg and define its tissue distribution. Mass spectrometry is helpful in difficult cases. Conditions caused by direct tissue deposition of MIg include common disorders, such as cast nephropathy, amyloidosis, and MIg deposition diseases, as well as uncommon disorders, such as immunotactoid glomerulopathy, proliferative GN with MIg deposits, light-chain proximal tubulopathy, and the rare entities of crystal-storing histiocytosis and crystalglobulinemia. Indirect mechanisms of MIg-induced renal disease can cause C3 glomerulopathy or thrombotic microangiopathy without tissue MIg deposits. Treatment of MIg-associated renal disease is aimed at eliminating the clonal plasma cell or B-cell population as appropriate. Both the renal and the underlying hematologic disorders influence the management and prognosis of MIg-associated renal diseases.
A PEGylated fibroblast growth factor 21 variant improves hepatic steatosis in a mouse model of non-alcoholic steatohepatitis, as determined by magnetic resonance imaging-derived hepatic fat-fraction
Authors: H. Tang, M. Fronheiser, S. Boehm, A. Pena, A. Shorts, B. Zinker, J. Krupinski, H. Malone, P. Chow, E. Charles, S. Du, W. Hayes
Journal: Journal of Hepatology (2018)
Effects of a PEGylated fibroblast growth factor 21 variant on steatosis, inflammation, and fibrosis in a mouse model of nonalcoholic steatohepatitis
Authors: B. Zinker, S. Boehm, S. Gao, A. He, B. Strassle, P. Morin, R. Christian, J. Krupinski
Journal: Journal of Hepatology (2018)
Interpreting heterogeneity in intestinal tuft cell structure and function
Authors: Amrita Banerjee, Eliot T McKinley, Jakob von Moltke, Robert J Coffey, Ken S Lau
Journal: Journal of Clinical Investigation (2018)

Intestinal tuft cells are a morphologically unique cell type, best characterized by striking microvilli that form an apical tuft. These cells represent approximately 0.5% of gut epithelial cells depending on location. While they are known to express chemosensory receptors, their function has remained unclear. Recently, numerous groups have revealed startling insights into intestinal tuft cell biology. Here, we review the latest developments in understanding this peculiar cell type’s structure and function. Recent advances in volumetric microscopy have begun to elucidate tuft cell ultrastructure with respect to its cellular neighbors. Moreover, single-cell approaches have revealed greater diversity in the tuft cell population than previously appreciated and uncovered novel markers to characterize this heterogeneity. Finally, advanced model systems have revealed tuft cells’ roles in mucosal healing and orchestrating type 2 immunity against eukaryotic infection. While much remains unknown about intestinal tuft cells, these critical advances have illuminated the physiological importance of these previously understudied cells and provided experimentally tractable tools to interrogate this rare cell population. Tuft cells act as luminal sensors, linking the luminal microbiome to the host immune system, which may make them a potent clinical target for modulating host response to a variety of acute or chronic immune-driven conditions.
Large deletion in 6q associated to A20 haploinsufficiency and thoracoabdominal heterotaxy
Authors: Sébastien Viel, Elodie Cheyssac, Rémi Pescarmona, Laurie Besson, Marianne Till, Loïc Viremouneix, Isabelle Touitou, Guillaume Sarrabay, Thierry Walzer, Alexandre Belot
Journal: Annals of the Rheumatic Diseases (2018)

Mutations in the TNFAIP3 gene resulting in A20 haploinsufficiency (HA20) have been identified as a new cause of autoinflammation linked to uncontrolled nuclear factor kappa B (NF-κB) activation.1 A recent report published in the  Annals of the Rheumatic Diseases highlighted the main clinical manifestations of the 16 patients who presented with recurrent oral, genital, gastrointestinal ulcerations and various inflammatory features (skin lesions, musculoskeletal disorders and recurrent fever) associated in some cases to autoimmunity mimicking a lupus.2 Some of the patients also experienced recurrent infections. TNFAIP3 anomalies included monoallelic nonsense and frameshift mutations.1 

Here, we report that HA20 can be part of a more complex genetic syndrome. We describe the new case of a boy who presented with mild intellectual disability with normal MRI and dysmorphic features including short stature, large forehead, thin lips and visible muscles (figure 1A). Of note, he had a heterotaxis with …
Evaluation of a hepatitis C virus core antigen assay in dried-blood spots: a cohort study
Authors: F. Lamoury, S. Bajis, D. Martinez, Y. Mowat, I. Jayasinghe, M. Martinez, P. Cunningham, B. Catlett, B. Jacka, P. Marks, J. Grebely, G. Cloherty, G. Dore, T. Applegate
Journal: Journal of Hepatology (2018)
Resistance analysis of hepatitis C virus NS5A gene in Brazilian patients infected with genotypes 1 and 3 treated with Daclatasvir
Authors: V. Costa, C. Brandão-Mello, M.M.A. Pires, F.C.D.A. Mello, P.G.C.S. Silva, E.P. Nunes, L.L. Lewis-Ximenez, E. Lampe
Journal: Journal of Hepatology (2018)
Chronic kidney disease in patients with cirrhosis surviving an episode of acute kidney injury. Frequency and impact on patient’s outcome
Authors: O. Bassegoda, P. Huelin, E. Pose, L. Napoleone, A. Juanola, R. Moreira, M. Carol, G. De Prada, N. Fabrellas, C. Solé, I. Graupera, E. Solà, P. Ginès
Journal: Journal of Hepatology (2018)
TCTAP A-134 Clinical and Anatomical Predictors of Side Branch Problems in True Bifurcation Lesions Treated by Provisional Strategy
Authors: Osama Mamdouh Shoeib, Francesco Burzotta, Cristina Aurigemma, Antonio Maria Leone, Italo Porto, Lorenzo Genuardi, Carlo Trani
Journal: Journal of the American College of Cardiology (2018)
A phase I dose-escalation trial of intraperitoneal oxaliplatin with systemic capecitabine and bevacizumab following cytoreduction in patients with peritoneal carcinomatosis from appendiceal or colorectal cancer.
Authors: Aabha Oza, Patrick Grierson, Sean Glasgow, Katrina Pedersen, Stephen Barman, Thomas Westbrook, Matthew G Mutch, Andrea Wang-Gillam, Rama Suresh, Ashley Morton, Samantha Marquez, James W Fleshman, Benjamin R. Tan
Journal: Journal of Clinical Oncology (2018)

746 Background: Peritoneal carcinomatosis (PC) is the intraperitoneal spread of cancer. Optimal treatment for PC is controversial. Systemic chemotherapy offers limited benefit (Franko, 2011). Intraperitoneal (IP) chemotherapy following cytoreductive surgery (CRS) improves outcomes (Verwaal, 2008). Oxaliplatin (Ox), capecitabine, and bevacizumab are standard agents for the treatment of metastatic colorectal cancer (CRC). Evidence suggests benefit of IP Ox at high doses. However, the optimal dose of IP Ox combined with standard systemic therapy is unclear. Methods: We conducted an IRB-approved phase I dose-escalation study of IP Ox D1 at 25mg/m2-100mg/m2, with systemic bevacizumab D1 at 5mg/kg, and capecitabine 850mg/m2 BID for 7 days (cycle = 14 days), in patients with PC from appendiceal or CRC after CRS. The primary aim was to determine the recommended phase II dose (RP2D)/maximum tolerated dose (MTD) for this regimen. Dose limiting toxicities (DLTs) were assessed during cycle 1. DLTs included grade 3 or 4 non-hematological toxicities, or grade 4 hematological toxicities. Results: 18 patients (12 females, median age 56) were enrolled on the study. No DLTs were observed during cycle 1 in the first 4 cohorts. One DLT (abdominal pain) was observed in cohort 5. Another patient in cohort 5 experienced grade 3 abdominal pain soon after cycle 2, thus limiting repeated treatment for this cohort. Other toxicities included fatigue (72%), nausea (61%), peripheral neuropathy (50%), constipation (50%), mucositis (39%) and dizziness (39%). See table below for average # of cycles per cohort and responses. Conclusions: IP Ox combined with capecitabine and bevacizumab is feasible. Our recommended dose for IP Ox is 85 mg/m2 with systemic therapy (cohort 4). An expansion cohort is underway for this dose level. Based on these data, further investigation of IP Ox with systemic chemotherapy for PC is warranted. Clinical trial information: NCT01061515. [Table: see text]
Improving the efficacy of hepatocyte transplantation using alpha-1 antitrypsin as an immune modulator
Authors: C. Lee, A. Dhawan, C. Filippi, R. Mitry, V. Iansante, R.F. Dacosta, S. Lehec, A. Chandrashekran, T. Strom, M. Koulmanda, E. Fitzpatrick
Journal: Journal of Hepatology (2018)
Lower risk of multiple sclerosis in patients with chronic hepatitis C: A nationwide population-based register study 2001-2013
Authors: J. Söderholm, A. Yilmaz, K. Buesch, R. Wejstál, A. Brolund, J. Kövamees, M. Sällberg, M. Lagging, M. Gisslén
Journal: Journal of Hepatology (2018)
Multikinase Inhibitor CT-707 Targets Liver Cancer by Interrupting the Hypoxia-Activated IGF-1R–YAP Axis
Authors: Hong Zhu, Dan-Dan Wang, Tao Yuan, Fang-Jie Yan, Chen-Ming Zeng, Xiao-Yang Dai, Zi-bo Chen, Ying Chen, Tianyi Zhou, Guang-Han Fan, Meidan Ying, Ji Cao, Peihua Luo, Xi-Jie Liu, Yuandong Hu, Yong Peng, Qiaojun He, Bo Yang
Journal: Cancer Research (2018)

Abstract Given that Yes-associated protein (YAP) signaling acts as a critical survival input for hypoxic cancer cells in hepatocellular carcinoma (HCC), disruption of YAP function and the maintenance of hypoxia is an attractive way to treat HCC. Utilizing a cell-based YAP-TEAD luciferase reporter assay and functional analyses, we identified CT-707, a China-FDA approved multi-kinase inhibitor under clinical trial with remarkable inhibitory activity against YAP function. CT-707 exhibited prominent cytotoxicity under hypoxia on HCC cells, which was attributable to the inhibition of YAP signaling. CT-707 arrested tumor growth in HepG2, Bel-7402, and HCC patient-derived xenografts. Mechanistically, the inhibitory activity of CT-707 on YAP signaling was due to the interruption of hypoxia-activated IGF1R. Overall, these findings not only identify CT-707 as a promising hypoxia-targeting agent against HCC, but they also unveil IGF1R as a new modulator specifically regulating hypoxia-activated YAP signaling. Significance: CT-707 may represent a novel clinical approach for patients with HCC suffering poor drug response due to intratumor hypoxia. Cancer Res; 78(14); 3995–4006. ©2018 AACR.
234Models for VEGF-B induced physiological and pathological cardiac hypertrophy
Authors: M O H Rasanen, K Amudhala Hemanthakumar, J B Paech, M R Robciuc, D Ramanujam, J B Lahteenvuo, S Engelhardt, R Kivela, K Alitalo
Journal: Cardiovascular Research (2018)

pharmacological inhibition of the inositol triphosphate (IP3)-activated calcium channel or the mitochondrial calcium uniporter.Gain of function studies confirm that myocardin can desensitize myocytes to permeability transition elicited by protein kinase-A (PKA) activating agents by opposing SR calcium release.Furthermore, restoring microRNA-133a function with mimicking oligonucleotides, or knockdown of Nix rescues mitochondrial calcium accumulation induced by myocardin knockdown.Molecular studies using Nix constructs targeted to the SR or mitochondria revealed that only SR-targeted Nix leads to mitochondrial calcium accumulation, which could be attenuated by SR-targeted Bcl-2, but not mitochondrial-targeted Bcl-2.Finally, we observed reduced myocardin expression in vivo within the infarction border zone following coronary ligation in rodents, with corresponding reduced microRNA-133a and elevated Nix expression.These findings identify a novel myocardin-regulated genetic pathway that maintains cardiomyocyte calcium homeostasis and mitochondrial function during development, and is attenuated during ischemic heart disease.
European Commission moves to boost vaccination cover across the continent
Authors: Rory Watson
Journal: BMJ (2018)

The European Commission has tabled wide ranging recommendations to increase the uptake of vaccinations against preventable diseases.1 These aim to reassure the public of the safety and benefits of vaccines and to tackle the upsurge in Europe of infectious diseases such as measles.

Vaccination programmes have become increasingly fragile, the commission notes, because of low uptake of vaccines, vaccine hesitancy, increasing costs, and production and supply shortages.

Presenting the strategy on 26 April, Vytenis Andriukaitis, the European health and food safety commissioner, said, “Vaccination is one of the most powerful and cost effective public health measures developed in the …
Incidence of de-novo hepatocellular carcinoma after treatment with direct antiviral agents for hepatitis C: A multicenter prospective cohort study from Latin America
Authors: F. Piñero, E. Ridruejo, M. Mendizabal, C. Alonso, A. Varon, A. Soza, A. Palazzo, M. Sixto, N. Hernandez, M.I. Schinoni, S. Ceballos, C. Gadea, D. Perez, M.V. Reggiardo, V. Moreno, S.E. Mengarelli, A. Bruno, C. Mendoza, J. Vila, F. Barreyro, M.G.V. Zuain, Raymundo Parana Filho, M. Silva
Journal: Journal of Hepatology (2018)
Genetic analysis of therapy-related myeloid neoplasms occurring after intensive treatment for acute promyelocytic leukemia
Authors: Aline Renneville, Philippe Attias, Xavier Thomas, Cécile Bally, Sandrine Hayette, Hassan Farhat, Virginie Eclache, Alice Marceau-Renaut, Bruno Cassinat, Jean Feuillard, Christine Terré, Eric Delabesse, Sophie Park, Julie Lejeune, Sylvie Chevret, Lionel Adès, Claude Preudhomme, Pierre Fenaux
Journal: Leukemia (2018)
Cabozantinib as a Second-Line Agent in Advanced Hepatocellular Carcinoma
Authors: Masatoshi Kudo
Journal: Liver Cancer (2018)

The results of the phase III CELESTIAL trial of cabozantinib were presented by Prof. Ghassan Abou-Alfa at the ASCO Gastrointestinal Cancer Symposium held in San Francisco from January 18 to 20, 2018 [1]. Although most of the previous clinical trials of second-line agents, except regorafenib [2], failed [3, 4, 5, 6, 7, 8], the CELESTIAL trial yielded positive results in line with most expectations and produced a fourth molecular-targeted drug option for hepatocellular carcinoma (HCC). Based on this trial, cabozantinib can be added as a second-line option to the first-line drugs sorafenib [9, 10] and lenvatinib [11] and the second-line drug regorafenib [2] (Table ​(Table11).

Table 1

Phase III clinical trials of advanced stage HCC
Immune cell census in murine atherosclerosis: cytometry by time of flight illuminates vascular myeloid cell diversity
Authors: Jennifer E Cole, Inhye Park, David J Ahern, Christina Kassiteridi, Dina Danso Abeam, Michael E Goddard, Patricia Green, Pasquale Maffia, Claudia Monaco
Journal: Cardiovascular Research (2018)

Atherosclerosis is characterized by the abundant infiltration of myeloid cells starting at early stages of disease. Myeloid cells are key players in vascular immunity during atherogenesis. However, the subsets of vascular myeloid cells have eluded resolution due to shared marker expression and atypical heterogeneity in vascular tissues. We applied the high-dimensionality of mass cytometry to the study of myeloid cell subsets in atherosclerosis. Apolipoprotein E-deficient (ApoE−/−) mice were fed a chow or a high fat (western) diet for 12 weeks. Single-cell aortic preparations were probed with a panel of 35 metal-conjugated antibodies using cytometry by time of flight (CyTOF). Clustering of marker expression on live CD45+ cells from the aortas of ApoE−/− mice identified 13 broad populations of leucocytes. Monocyte, macrophage, type 1 and type 2 conventional dendritic cell (cDC1 and cDC2), plasmacytoid dendritic cell (pDC), neutrophil, eosinophil, B cell, CD4+ and CD8+ T cell, γδ T cell, natural killer (NK) cell, and innate lymphoid cell (ILC) populations accounted for approximately 95% of the live CD45+ aortic cells. Automated clustering algorithms applied to the Lin-CD11blo-hi cells revealed 20 clusters of myeloid cells. Comparison between chow and high fat fed animals revealed increases in monocytes (both Ly6C+ and Ly6C−), pDC, and a CD11c+ macrophage subset with high fat feeding. Concomitantly, the proportions of CD206+ CD169+ subsets of macrophages were significantly reduced as were cDC2. A CyTOF-based comprehensive mapping of the immune cell subsets within atherosclerotic aortas from ApoE−/− mice offers tools for myeloid cell discrimination within the vascular compartment and it reveals that high fat feeding skews the myeloid cell repertoire toward inflammatory monocyte-macrophage populations rather than resident macrophage phenotypes and cDC2 during atherogenesis.
European interlaboratory comparison of breath (CO2)-C-13 analysis
Authors: F Stellaard, B Geypens
Journal: Gut (1998)

The BIOMED I programme Stable Isotopes in Gastroenterology and Nutrition (SIGN) has focused upon evaluation and standardisation of stable isotope breath tests using C-13 labelled substrates. The programme dealt with comparison of C-13 substrates, test meats, test conditions, analysis techniques, and calculation procedures. Analytical techniques applied for (CO2)-C-13 analysis were evaluated by taking an inventory of instrumentation, calibration protocols, and analysis procedures. Two ring tests were initiated measuring C-13 abundances of carbonate materials. Evaluating the data it was found that seven different models of isotope ratio mass spectrometers (IRMS) were used by the participants applying both the dual inlet system and the continuous flow configuration. Eight different brands of certified C-13 reference materials were used with a C-13 abundance varying from delta(13)C(PDB) -37.2 to +2.0 parts per thousand. CO2 was liberated from certified material by three techniques and different working standards were used varying from -47.4 to +0.4 parts per thousand in their delta(13)C(PDB) value. The standard deviations (SDs) found for all measurements by all participants were 0.25 parts per thousand and 0.50 parts per thousand for two carbonates used in the ring tests. The individual variation for the single participants varied from 0.02 parts per thousand (dual inlet system) to 0.14 parts per thousand (continuous flow system). The measurement of the difference between two carbonates showed a SD of 0.33 parts per thousand calculated for all participants. Internal precision of IRMS as indicated by the specifications of the different instrument suppliers is
Nox2 in regulatory T cells promotes angiotensin II–induced cardiovascular remodeling
Authors: Amber Emmerson, Silvia Cellone Trevelin, Heloise Mongue-Din, Pablo D. Becker, Carla Ortiz, Lesley A. Smyth, Qi Peng, Raul Elgueta, Greta Sawyer, Aleksandar Ivetic, Robert I. Lechler, Giovanna Lombardi, Ajay M. Shah
Journal: Journal of Clinical Investigation (2018)

The superoxide-generating enzyme Nox2 contributes to hypertension and cardiovascular remodeling triggered by activation of the renin-angiotensin system. Multiple Nox2-expressing cells are implicated in angiotensin II-induced (Ang II-induced) pathophysiology, but the importance of Nox2 in leukocyte subsets is poorly understood. Here, we investigated the role of Nox2 in T cells, particularly Tregs. Mice globally deficient in Nox2 displayed increased numbers of Tregs in the heart at baseline, whereas Ang II-induced effector T cell (Teff) infiltration was inhibited. To investigate the role of Treg Nox2, we generated a mouse line with CD4-targeted Nox2 deficiency (Nox2fl/flCD4Cre+). These animals showed inhibition of Ang II-induced hypertension and cardiac remodeling related to increased tissue-resident Tregs and reduction in infiltrating Teffs, including Th17 cells. The protection in Nox2fl/flCD4Cre+ mice was reversed by anti-CD25 antibody depletion of Tregs. Mechanistically, Nox2-/y Tregs showed higher in vitro suppression of Teff proliferation than WT Tregs, increased nuclear levels of FoxP3 and NF-κB, and enhanced transcription of CD25, CD39, and CD73. Adoptive transfer of Tregs confirmed that Nox2-deficient cells had greater inhibitory effects on Ang II-induced heart remodeling than WT cells. These results identify a previously unrecognized role of Nox2 in modulating suppression of Tregs, which acts to enhance hypertension and cardiac remodeling.