tbuckley/cabot-search huggingface dataset:
HBV-specific T cell responses in low replicating inactive carrier patients are independent of Hepatitis B surface antigen load
Authors: U.S. Gill, N. Hansi, N.L. Bert, K. Kunasegaran, G.E. Dolman, D. Tan, W. Tong, M. Maini, A. Bertoletti, P. Kennedy
Journal: Journal of Hepatology (2018)
P117GDF-15 and sST2 as biomarkers for arrhythmic death in non ischemic heart failure
Authors: S Demyanets, S Stojkovic, A Kaider, L Koller, M Brekalo, A Diedrich, J Wojta, T Pezawas
Journal: Cardiovascular Research (2018)

Objective: To study structural parameters of vessel wall, lipid and inflammatory biochemical parameters in patients with arterial hypertensios (AH) and abdominal obesity (AO).Design and methods: 108 patients (mean age 44,8160,95) were randomized into 2 groups.The Gr.1 included 70 subjects with AH and AO.The Gr.2 included 38 subjects without AO.The parameters of sphygmography, blood pressure monitoring; biochemical parameters (total cholesterol, LDL-chol, HDL-chol, triglycerides, malonic dialdehyde and inflammatory markers -homocysteine and hs-CRP were estimated.Results: In Gr.1 there were registered: significant increase in sphygmography indexis (pulse wave velocity PWV, cardio-ankle vascular index ), in mean 24-hour and mean daytime systolic BP and variability, in total cholesterol, LDL-chol, triglyceride and MD levels, homocysteine and hs-CRP level, compared to the patients in group 2.In Gr.1 there were registered positive correlation between inflammatory and lipid markers with parameters of sphygmography and blood pressure monitoring.It was shown that with an increase in total cholesterol level >5.0 mmol/l, the risk of high rate PWV in patients with AH and AO increased by 15 times. Conclusion:The revealed correlations of inflammatory and lipid markers with indices of vascular wall rigidity once again exhibit a high risk of cerebrovascular complications in patients with AH and metabolic disorders
Evolving diagnostic pathways in liver disease: using quantitative magnetic resonance imaging to distinguish parenchymal and biliary disease
Authors: K. Arndtz, B. Irving, S.M. Brady, N. Jayaratne, P. Eddowes, M. Kelly, D. Green, R. Banerjee, S. Neubauer, G. Hirschfield
Journal: Journal of Hepatology (2018)
Sex‐ and age‐based differences in the natural history and outcome of dilated cardiomyopathy
Authors: Brian P. Halliday, Ankur Gulati, Aamir Ali, Simon Newsome, Amrit Lota, Upasana Tayal, Vassilios S. Vassiliou, Monika Arzanauskaite, Cemil Izgi, Kaushiga Krishnathasan, Arvind Singhal, Kayla Chiew, John Gregson, Michael P. Frenneaux, Stuart A. Cook, Dudley J. Pennell, Peter Collins, John G.F. Cleland, Sanjay K. Prasad
Journal: European Journal of Heart Failure (2018)

Aim To evaluate the relationship between sex, age and outcome in dilated cardiomyopathy (DCM). Methods and results We used proportional hazard modelling to examine the association between sex, age and all‐cause mortality in consecutive patients with DCM. Overall, 881 patients (290 women, median age 52 years) were followed for a median of 4.9 years. Women were more likely to present with heart failure (64.0% vs. 54.5%; P = 0.007) and had more severe symptoms ( P &lt; 0.0001) compared to men. Women had smaller left ventricular end‐diastolic volume (125 mL/m 2 vs. 135 mL/m 2 ; P &lt; 0.001), higher left ventricular ejection fraction (40.2% vs. 37.9%; P = 0.019) and were less likely to have mid‐wall late gadolinium enhancement (23.0% vs. 38.9%; P &lt; 0.0001). During follow‐up, 149 (16.9%) patients died, including 41 (4.7%) who died suddenly. After adjustment, all‐cause mortality [hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.41–0.92; P = 0.018] was lower in women, with similar trends for cardiovascular (HR 0.60, 95% CI 0.35–1.05; P = 0.07), non‐sudden (HR 0.63, 95% CI 0.39–1.02; P = 0.06) and sudden death (HR 0.70, 95% CI 0.30–1.63; P = 0.41). All‐cause mortality (per 10 years: HR 1.36, 95% CI 1.20–1.55; P &lt; 0.0001) and non‐sudden death (per 10 years: HR 1.51, 95% CI 1.26–1.82; P &lt; 0.00001) increased with age. Cumulative incidence curves confirmed favourable outcomes, particularly in women and those &lt;60 years. Increased all‐cause mortality in patients &gt;60 years of age was driven by non‐sudden death. Conclusion Women with DCM have better survival compared to men, which may partly be due to less severe left ventricular dysfunction and a smaller scar burden. There is increased mortality driven by non‐sudden death in patients &gt;60 years of age that is less marked in women. Outcomes with contemporary treatment were favourable, with a low incidence of sudden death.
The DOT1L inhibitor pinometostat reduces H3K79 methylation and has modest clinical activity in adult acute leukemia
Authors: Eytan M. Stein, Guillermo Garcia-Manero, David A. Rizzieri, Raoul Tibes, Jesus G. Berdeja, Michael R. Savona, Mojca Jongen-Lavrenic, Jessica K. Altman, Blythe Thomson, Stephen J. Blakemore, Scott R. Daigle, Nigel J. Waters, A. Benjamin Suttle, Alicia Clawson, Roy Pollock, Andrei Krivtsov, Scott A. Armstrong, Jorge DiMartino, Eric Hedrick, Bob Löwenberg, Martin S. Tallman
Journal: Blood (2018)
P536Adipocytes are coagulant active in a TF/FVIIa dependent manner but lipolysis is unaffected by TF/FVIIa
Authors: D Eden, D Mokhtari, J W Eriksson, M Aberg, A Siegbahn
Journal: Cardiovascular Research (2018)

Adipocytes are coagulant active in a TF/FVIIa dependent manner but lipolysis is unaffected by TF/FVIIa
Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D)
Authors: Annie M. Young, Andrea Marshall, Jenny Thirlwall, Oliver Chapman, Anand Lokare, Catherine Hill, Danielle Hale, Janet A. Dunn, Gary H. Lyman, Charles Hutchinson, Peter MacCallum, Ajay Kakkar, F.D. Richard Hobbs, Stavros Petrou, Jeremy Dale, Christopher J. Poole, Anthony Maraveyas, Mark Levine
Journal: Journal of Clinical Oncology (2018)

Purpose Venous thromboembolism (VTE) is common in patients with cancer. Long-term daily subcutaneous low molecular weight heparin has been standard treatment for such patients. The purpose of this study was to assess if an oral factor Xa inhibitor, rivaroxaban, would offer an alternative treatment for VTE in patients with cancer. Patient and Methods In this multicenter, randomized, open-label, pilot trial in the United Kingdom, patients with active cancer who had symptomatic pulmonary embolism (PE), incidental PE, or symptomatic lower-extremity proximal deep vein thrombosis (DVT) were recruited. Allocation was to dalteparin (200 IU/kg daily during month 1, then 150 IU/kg daily for months 2-6) or rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily for a total of 6 months). The primary outcome was VTE recurrence over 6 months. Safety was assessed by major bleeding and clinically relevant nonmajor bleeding (CRNMB). A sample size of 400 patients would provide estimates of VTE recurrence to within ± 4.5%, assuming a VTE recurrence rate at 6 months of 10%. Results A total of 203 patients were randomly assigned to each group, 58% of whom had metastases. Twenty-six patients experienced recurrent VTE (dalteparin, n = 18; rivaroxaban, n = 8). The 6-month cumulative VTE recurrence rate was 11% (95% CI, 7% to 16%) with dalteparin and 4% (95% CI, 2% to 9%) with rivaroxaban (hazard ratio [HR], 0.43; 95% CI, 0.19 to 0.99). The 6-month cumulative rate of major bleeding was 4% (95% CI, 2% to 8%) for dalteparin and 6% (95% CI, 3% to 11%) for rivaroxaban (HR, 1.83; 95% CI, 0.68 to 4.96). Corresponding rates of CRNMB were 4% (95% CI, 2% to 9%) and 13% (95% CI, 9% to 19%), respectively (HR, 3.76; 95% CI, 1.63 to 8.69). Conclusion Rivaroxaban was associated with relatively low VTE recurrence but higher CRNMB compared with dalteparin.
Combined photodynamic therapy with systemic chemotherapy improves survival of patients with irresectable cholangiocarcinoma
Authors: M.A. Gonzalez-Carmona, M. Bolch, C. Jansen, A. Vogt, M. Sampels, K. van Beekum, R. Mahn, M. Praktiknjo, J. Nattermann, J. Trebicka, V. Branchi, H. Matthaei, S. Manekeller, J. Kalff, C.P. Strassburg, T. Weismüller
Journal: Journal of Hepatology (2018)
<i>In vivo</i>visualisation of different modes of action of biological DMARDs inhibiting osteoclastic bone resorption
Authors: Yoshinobu Matsuura, Junichi Kikuta, Yuika Kishi, Tetsuo Hasegawa, Daisuke Okuzaki, Toru Hirano, Masafumi Minoshima, Kazuya Kikuchi, Atsushi Kumanogoh, Masaru Ishii
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> Osteoclasts play critical roles in inflammatory bone destruction. Precursor cell migration, cell differentiation, and functional cell activation are all in play. Biological disease-modifying antirheumatic drugs (DMARDs) have been shown to significantly inhibit both bone erosion as well as synovitis, although how such agents reduce osteoclastic bone destruction<i>in vivo</i> has not been fully explained. Here, we used an intravital time-lapse imaging technique to directly visualise mature osteoclasts and their precursors, and explored how different biological DMARDs acted <i>in vivo</i>. <h3>Methods</h3> Lipopolysaccharide (LPS) was injected into the calvarial periosteum of fluorescent reporter mice to induce inflammatory bone destruction. Time-lapse imaging was performed via intravital multiphoton microscopy 5 days after LPS injection. Biological DMARDs, including monoclonal antibodies (mAbs) against the interleukin (IL) 6 receptor (IL-6R) and tumour necrosis factor α (TNFα), or cytotoxic T-lymphocyte-associated protein 4 (CTLA4)-Ig, were intraperitoneally administered at the time of LPS injection. We determined CD80/86 expression levels in mature osteoclasts and their precursors by flow cytometry, quantitative PCR and immunohistochemistry. <h3>Results</h3> Of the biologicals tested, anti-IL-6R and anti-TNFα mAbs affected mature osteoclasts and switched bone-resorbing osteoclasts to non-resorbing cells. CTLA4-Ig had no action on mature osteoclasts but mobilised osteoclast precursors, eliminating their firm attachment to bone surfaces. In agreement with these results, CD80/86 (the target molecules of CTLA4-Ig) were prominently expressed only in osteoclast precursor cells, being suppressed during osteoclast maturation. <h3>Conclusions</h3> Intravital imaging revealed that various biological DMARDs acted at specific therapeutic time points during osteoclastic bone destruction, with different efficacies. These results enable us to grasp the real modes of action of drugs, optimising the usage of drug regimens.
Abstract 18251: Establishment of an in vitro Platform, the Hydrogel Mattress, to Enhance Maturation and Evaluate Contractile Function of Individual hiPSC-CMs
Authors: Tromondae K Feaster, Charles H Williams, Lili Wang, Adrian G Cadar, Young W Chun, Chee C Lim, Bjorn C Knollmann, Charles C Hong
Journal: Circulation (2015)

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have great potential as tools for cell based therapy, disease modeling and drug discovery. However, their contractile properties have not been routinely evaluated; as methods to do so are cumbersome and not easily translated to standard laboratories. We sought to develop a more efficient protocol to evaluate hiPSC-CM mechanical properties, at the single cell level. Individual hiPSC-CMs were cultured on a hydrogel based platform, termed the hydrogel mattress, and their cellular contractile properties were evaluated using video based edge detection (Figure A). We found individual hiPSC-CMs maintained for 5 days on the mattress assumed an elongated shape (Figure B) and exhibited robust, reproducible cell shortening (~10% versus &lt;1% for standard culture). We further found hiPSC-CM cellular contraction and peak cell shortening amplitude was comparable to that of freshly isolated adult rabbit and mouse ventricular CMs (Figure C). In addition, hiPSC-CMs maintained on the mattress exhibited characteristics of mature CMs including action potential waveform, calcium handling and pharmacological response to myofilament calcium sensitizers. We further show a positive correlation with the established traction force microscopy method. We demonstrate the hydrogel mattress platform enables routine characterization and quantification of contractile performance of isolated hiPSC-CMs. This platform can be extended to in vitro disease modeling, drug discovery and drug induced cardiotoxicity testing. Further, the mattress can be easily adapted to virtually any laboratory, thus streamlining cellular mechanical evaluation of individual hiPSC-CMs in vitro.
Sixty seconds on . . . free breakfast
Authors: Abi Rimmer
Journal: BMJ (2018)

There is if you’re a junior doctor who has just come off a night shift at Northampton General Hospital. Since August the trust has been offering all trainees the chance to tuck into bacon and eggs after a night shift for free.

It’s actually the brainchild of the trust’s chief executive, Sonia Swart. A doctor herself, Swart thought it would be a good way to make junior doctors feel valued, as part of …
Poor outcome of acute hepatitis E in liver cirrhosis and transplant recipients
Authors: M.R. Barciela, A. Barreira, M. Bermúdez, J. Llaneras, E. Mena, S. Romero, M.V. Cots, F. Sanpedro, M.B. Ferret, R. Esteban
Journal: Journal of Hepatology (2018)
Polypyrrole-chitosan conductive biomaterial synchronizes cardiomyocyte contraction and improves myocardial electrical impulse propagation
Authors: Zhi Cui, Nathan C. Ni, Jun Wu, Guo-Qing Du, Sheng He, Terrence M. Yau, Richard D. Weisel, Hsing-Wen Sung, Ren-Ke Li
Journal: Theranostics (2018)

Background:The post-myocardial infarction (MI) scar interrupts electrical impulse propagation and delays regional contraction, which contributes to ventricular dysfunction.We investigated the potential of an injectable conductive biomaterial to restore scar tissue conductivity and re-establish synchronous ventricular contraction.Methods: A conductive biomaterial was generated by conjugating conductive polypyrrole (PPY) onto chitosan (CHI) backbones.Trypan blue staining of neonatal rat cardiomyocytes (CMs) cultured on biomaterials was used to evaluate the biocompatibility of the conductive biomaterials.Ca 2+ imaging was used to visualize beating CMs.A cryoablation injury rat model was used to investigate the ability of PPY:CHI to improve cardiac electrical propagation in the injured heart in vivo.Electromyography was used to evaluate conductivity of scar tissue ex vivo.Results: Cell survival and morphology were similar between cells cultured on biomaterials-coated and uncoated-control dishes.PPY:CHI established synchronous contraction of two distinct clusters of spontaneously-beating CMs.Intramyocardial PPY:CHI injection into the cryoablation-induced injured region improved electrical impulse propagation across the scarred tissue and decreased the QRS interval, whereas saline-or CHI-injected hearts continued to have delayed propagation patterns and significantly reduced conduction velocity compared to healthy controls.Ex vivo evaluation found that scar tissue from PPY:CHI-treated rat hearts had higher signal amplitude compared to those from saline-or CHI-treated rat heart tissue.Conclusions: The PPY:CHI biomaterial is electrically conductive, biocompatible and injectable.It improved synchronous contraction between physically separated beating CM clusters in vitro.Intra-myocardial injection of PPY:CHI following cardiac injury improved electrical impulse propagation of scar tissue in vivo.
Tenofovir is more potent over entecavir in reducing the viral load in patients of hepatitis B reactivation presenting as Acute on Chronic Liver Failure (ACLF)-Results of multination study from APASL-ACLF Research Consortium (AARC)
Authors: J. Ahmad, A. Choudhury, M. Kumar, M. Al-Mahtab, S. Rahman, Q. Ning, K. Ma, Z. Duan, Y. Chen, J.H. Hu, J. Hu, S.-S. Tan, S.S. Hamid, A. Subhan, W. Jafri, L.A. Lesmana, R. Lesmana, H.L. Ghazinyan, J.-D. Jia, G.H. Lee, S.G. Lim, S. Taneja, Y. Chawla, G. Lau, M. Sahoo, A. Shukla, H. Deverbhavi, M.-F. Yuen, Z. Abbas, D. Amarapurkar, F. Karim, S. Treeprasertsuk, A.K. Dokmeci, A. Goel, C. Eapen, D. Payawal, S. Shah, C. Kalal, A. Kulkarni, S. Chaudhury, I. Paulson, P. Jain, G. Kumar, S.K. Sarin
Journal: Journal of Hepatology (2018)
Protein Tyrosine Phosphatase-N13 Promotes Myofibroblast Resistance to Apoptosis in Idiopathic Pulmonary Fibrosis
Authors: Alison Bamberg, Elizabeth F. Redente, Steve D. Groshong, Rubin M. Tuder, Carlyne D. Cool, Rebecca C. Keith, Benjamin L. Edelman, Bart P. Black, Gregory P. Cosgrove, Murry W. Wynes, Douglas Curran-Everett, Stijn De Langhe, Luis A. Ortiz, Andrew Thorburn, David W. H. Riches
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrotic interstitial lung disease characterized by (myo)fibroblast accumulation and collagen deposition. Resistance to Fas-induced apoptosis is thought to facilitate (myo)fibroblast persistence in fibrotic lung tissues by poorly understood mechanisms.
BGP: identifying gene-specific branching dynamics from single-cell data with a branching Gaussian process
Authors: Alexis Boukouvalas, James Hensman, Magnus Rattray
Journal: Genome biology (2018)

High-throughput single-cell gene expression experiments can be used to uncover branching dynamics in cell populations undergoing differentiation through pseudotime methods. We develop the branching Gaussian process (BGP), a non-parametric model that is able to identify branching dynamics for individual genes and provide an estimate of branching times for each gene with an associated credible region. We demonstrate the effectiveness of our method on simulated data, a single-cell RNA-seq haematopoiesis study and mouse embryonic stem cells generated using droplet barcoding. The method is robust to high levels of technical variation and dropout, which are common in single-cell data.
Bevacizumab Reduces S100A9-Positive MDSCs Linked to Intracranial Control in Patients with EGFR-Mutant Lung Adenocarcinoma
Authors: Po-Hao Feng, Kuan-Yuan Chen, Yu-Chen Huang, Ching-Shan Luo, Shen Ming Wu, Tzu-Tao Chen, Chun-Nin Lee, Chi-Tai Yeh, Hsiao-Chi Chuang, Chia-Li Han, Chiou-Feng Lin, Wei-Hwa Lee, Chih-Hsi Kuo, Kang-Yun Lee
Journal: Journal of Thoracic Oncology (2018)
Early-onset pediatric atopic dermatitis is characterized by TH2/TH17/TH22-centered inflammation and lipid alterations
Authors: Patrick M. Brunner, Ariel Israel, Ning Zhang, Alexandra Leonard, Huei-Chi Wen, Thy Huynh, Gary Tran, Sarah Lyon, Giselle Rodriguez, Supriya Immaneni, Annette Wagner, Xiuzhong Zheng, Yeriel D. Estrada, Hui Xu, James G. Krueger, Amy S. Paller, Emma Guttman-Yassky
Journal: Journal of Allergy and Clinical Immunology (2018)
Waldenström macroglobulinemia treatment algorithm 2018
Authors: Morie A. Gertz
Journal: Blood Cancer Journal (2018)

Waldenström macroglobulinemia is often an indolent disorder, and many patients are candidates for observation with careful monitoring. For symptomatic patients, one must distinguish between those patients whose symptoms are related to immunologic manifestations associated with the IgM monoclonal protein and those that have symptoms related to progressive marrow and nodal infiltration with lymphoplasmacytic lymphoma. In Waldenström macroglobulinemia, the driver for therapy in the majority of patients is progressive anemia, secondary to bone marrow replacement by lymphoplasmacytic lymphoma. Recent introduction of MYD88 mutational analysis has been very useful for diagnostic purposes but is unclear what effect it might have on the prognosis or response rate to therapy. An algorithm is provided on the management of asymptomatic individuals and the sequence used for chemotherapeutic intervention of symptomatic patients.
Good communication is key to good care
Authors: Sophie Cook
Journal: BMJ (2018)

For women with medical conditions the routine physical and emotional challenges of pregnancy are amplified by fluctuating symptoms and difficult treatment decisions that must balance risks and benefits to both mother and unborn child. Choosing the best option is rarely straightforward when drugs are needed. A discussion to consider the treatment options well before conception is helpful.

Valproate is a good example. An effective treatment for epilepsy, it is also licensed for bipolar disorder and, in some countries, migraine. …
Nemolizumab in patients with moderate-to-severe atopic dermatitis: Randomized, phase II, long-term extension study
Authors: Kenji Kabashima, Masutaka Furue, Jon M. Hanifin, Grazyna Pulka, Andreas Wollenberg, Ryszard Galus, Takafumi Etoh, Ryosuke Mihara, Miwa Nakano, Thomas Ruzicka
Journal: Journal of Allergy and Clinical Immunology (2018)

BackgroundNemolizumab, an anti–IL-31 receptor A mAb, improved pruritus, dermatitis, and sleep in adults with moderate-to-severe atopic dermatitis that was inadequately controlled by topical treatments in a phase II, 12-week, randomized, double-blind, placebo-controlled study (part A; NCT01986933).ObjectiveWe sought to assess the long-term efficacy and safety of nemolizumab injected subcutaneously every 4 weeks (Q4W) or every 8 weeks (Q8W) in a 52-week, double-blind extension (part B).MethodsDuring part B, patients continued the previous nemolizumab dose (0.1, 0.5, or 2.0 mg/kg Q4W or 2.0 mg/kg Q8W). Part B end points included percentage improvement from baseline in pruritus visual analog scale and dermatitis scores (including the Eczema Area and Severity Index).ResultsOverall, 216 of 264 patients completed part A, and 191 entered part B; 131 completed part B. In 153 patients randomized to nemolizumab in part A, improvement from baseline in pruritus visual analog scale score was maintained/increased from weeks 12 to 64, with greatest improvement in the 0.5-mg/kg Q4W group (percentage change from baseline at week 64: −73.0, −89.6, −74.7, and −79.1 in the 0.1-, 0.5-, and 2.0-mg/kg Q4W and 2.0-mg/kg Q8W groups, respectively). Improvement from baseline in dermatitis scores was also maintained/increased to week 64 (percentage change in Eczema Area and Severity Index score: −68.5, −75.8, −78.9, and −69.3 in the 0.1-, 0.5-, and 2.0-mg/kg Q4W and 2.0-mg/kg Q8W groups, respectively). Over 64 weeks, 83% to 89% had 1 or more adverse events, with no new safety concerns identified.ConclusionNemolizumab for up to 64 weeks was efficacious and overall well tolerated in patients with moderate-to-severe atopic dermatitis inadequately controlled by topical therapy.