tbuckley/cabot-search huggingface dataset:
Abstract 18283: Left Ventricular STIFFness vs. Fibrosis Quantification by T1 MAPping in Heart Failure With Preserved Ejection Fraction - STIFFMAP-HFpEF
Authors: Karl-Philipp Rommel, Max von Roeder, Thomas Stiermaier, Konrad Latuscynski, Christian Oberueck, Markus Sandri, Christian Lücke, Matthias Gutberlet, Gerhard Schuler, Philipp Lurz
Journal: Circulation (2015)

Introduction: Heart Failure with Preserved Ejection Fraction (HFpEF) is an increasing public health problem. To tailor successful treatment strategies it is essential to identify patients’ individual pathologies contributing to HFpEF. Cardiac magnetic resonance (CMR) derived T1-Mapping has been suggested as non-invasive tool to quantify diffuse myocardial fibrosis. Invasive tracings of pressure-volume relations represent the gold-standard for assessing load-independent mechanical diastolic properties of the left ventricle. Hypothesis: Aim of this study was therefore to elucidate the diagnostic performance of T1-Mapping in HFpEF patients by examining the relationship between the extracellular volume fraction (ECV) and invasively measured parameters of diastolic function and to study the potential of ECV to differentiate between different pathomechanisms in HFPEF. Methods: We performed CMR T1-Mapping in 21 patients with HFpEF and 11 patients without heart failure symptoms (further referred to as controls). Pressure volume loops were obtained with a conductance catheter during basal conditions and handgrip exercise. Transient preload reduction was used to extrapolate the diastolic stiffness constant. Results: Patients with HFpEF showed a higher extra cellular volume fraction (p=0.001), an elevated load-independent passive LV stiffness constant - ß (p&lt;0.001) and a longer time constant of active LV-relaxation Tau (p=0.04). ECV correlated well with ß (r =0.75, p &lt;0.001). After multivariate analysis, ECV remained the only independent predictor of ß. Within the HFpEF cohort, patients with ECV over median showed higher left ventricular masses (p=0.04) and a higher LV stiffness (p=0.05). ECV &lt; median identified patients with a prolonged active LV relaxation (p=0.008) and a marked hypertensive reaction to exercise due to a pathologic arterial elastance (p=0.05). Conclusions: Diffuse myocardial fibrosis, assessed by CMR derived T1-Mapping independently predicts invasively measured LV stiffness in HFpEF. In addition, ECV helps to non-invasively distinguish the role of impaired active relaxation and passive stiffness and refines characterization of patients, which represents a prerequisite for any successful therapy in the future.
Severe CNS angiostrongyliasis in a young marine: a case report and literature review
Authors: Liane McAuliffe, Shannon Fortin Ensign, Derek Larson, Mary Bavaro, Joseph Yetto, Michael Cathey, Mitsuru Mukaigawara, Masashi Narita, Kiyofumi Ohkusu, Timothy Quast, Charles Volk
Journal: The Lancet Infectious Diseases (2018)
Future research priorities for lichen sclerosus – results of a James Lind Alliance Priority Setting Partnership
Authors: R.C. Simpson, S.M. Cooper, G. Kirtschig, S. Larsen, S. Lawton, M. McPhee, R. Murphy, D. Nunns, S. Rees, M. Tarpey, K.S. Thomas
Journal: British Journal of Dermatology (2018)

Lichen sclerosus (LS) is a chronic, inflammatory genital skin condition affecting men, women and children.Long-term complications include loss of normal anatomy from scarring, and malignant transformation.Uncertainties exist about the cause, diagnosis and management of LS.For example, the aetiology is contested; evidence suggests that chronic irritation by occluded urine is important in males, 1 however, autoimmune mechanisms are proposed in females. 2 Genetic associations are suggested in both sexes. 2 Existing evidence on which to make recommendations about management and the prevention of malignancy, is generally poor quality. [2][4] We conducted a Priority Setting Partnership (PSP) from June 2017-July 2018 using James Lind Alliance (JLA) methodology 5 .The aim was to identify future research priorities about the causes, diagnosis, management and prevention of LS in men, women and children.
GSK tops ranking for making drugs available to poor people
Authors: Rebecca Coombes
Journal: BMJ (2018)

GSK, Novartis, Johnson and Johnson, and Merck KGaA have retained their 2016 positions as the leading drug companies in terms of making their products available to patients in low and middle income countries, an independent ranking shows.

The Access to Medicines (AtM) Index, published every two years, ranks 20 of the world’s largest pharmaceutical companies according to their work in this area.1

The bottom five companies are named as Bayer, Abbvie, Daiichi Sankyo, Astellas, and Eli Lilly. Of these five, only Bayer and Eli Lilly have strategies in place for improving access to drugs.

The index found that five companies were carrying out 63% of the most urgently needed research and development projects: GSK, Johnson and Johnson, Merck KGaA, Novartis, and Sanofi (fig 1).



Fig 1 
Ranking of 20 drug companies by numbers of priority R&D projects



The index has …
Development and validation of a multivariable risk prediction model for serious infection in patients with psoriasis receiving systemic therapy
Authors: Z.Z.N. Yiu, C. Sorbe, M. Lunt, S.J. Rustenbach, L. Kühl, M. Augustin, K.J. Mason, D.M. Ashcroft, C.E.M. Griffiths, R.B. Warren, Anthony D. Ormerod, Jonathan N.W.N. Barker, Ian Evans, Kathleen McElhone, Catherine H. Smith, Nick J. Reynolds, Ruth Murphy, Marilyn Benham, A. David Burden, Sagair Hussain, Brian Kirby, Linda Lawson, Caroline M. Owen
Journal: British Journal of Dermatology (2018)

Patients with psoriasis are often concerned about the risk of serious infection associated with systemic psoriasis treatments.
Plateletpheresis-associated lymphopenia in frequent platelet donors
Authors: John M. Gansner, Mahboubeh Rahmani, A. Helena Jonsson, Brooke M. Fortin, Idayat Brimah, Martha Ellis, Robin Smeland-Wagman, Zhihan J. Li, Jason M. Schenkel, Michael B. Brenner, Revital Yefidoff-Freedman, Steven R. Sloan, Nancy Berliner, Nicolas C. Issa, Lindsey R. Baden, Dan L. Longo, Duane R. Wesemann, Donna Neuberg, Deepak A. Rao, Richard M. Kaufman
Journal: Blood (2018)
THU0485 Predicting 1-year mortality after a fragility hip fracture – the experience of a fracture liaison service
Authors: F. Aguiar, M. Guerra, S. Ganhão, D. Gonçalves, T. Martins-Rocha, R.M. Ferreira, A. Águeda, R. Vieira, G. Terroso, C. Vaz, L. Costa
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Hip fractures are the most serious outcome of osteoporosis and are a leading public health concern due to the associated increase in morbidity and mortality, loss of independence and financial burden. <h3>Objectives</h3> The aim of this study was to investigate possible predictive factors of 1 year mortality in patients with fragility proximal femur fracture referred to a fracture liaison service (FLS). <h3>Methods</h3> Patients aged ≥65 years admitted in Orthopaedics department with a fragility hip fracture were evaluated and referred to the Rheumatology outpatient clinic. In this setting patients were evaluated with laboratorial and imagiological workup and afterwards anti-osteoporotic therapy was started. We retrospectively collected information regarding patients hospitalised from March 2015 to <sup>March 2017</sup> and conducted univariate and multivariate analysis to determine possible predictive factors of 1 year mortality. <h3>Results</h3> 522 patients were included, with a median age of 84 years (range 65–104), 416 (79.7%) females. The median time to intervention was 2 days (range 0–44) and median hospital stay 10 days (range 0–175). Median Charlson Comorbidity Index (CCI) score was 5 (range 2–13). In-hospital mortality was 6.3% and overall 1 year mortality was 16.7%. In the univariate analysis, the factors significantly associated with death in one year time were male gender, CCI score &gt;5, previous physical limitation in daily activities, walking disability previously and 2 months after the fracture, longer time to surgery (&gt;48 hour), conservative treatment and previous osteoporosis diagnosis. In multivariate analysis previous physical limitation in daily activities (OR 2.1, CI 1.22–3.62; p=0.007) and walking disability 2 months after the fracture (OR 4.23, CI 1.73–10.37; p=0.002) were independent predictors of 1 year mortality. <h3>Conclusions</h3> In this study, in-hospital mortality was similiar to what has been described in literature but 1 year mortality was slightly lower. Previous physical limitation and walking disability 2 months after the fracture were independent risk factors for 1 year mortality. These findings should be confirmed in larger, prospective studies with a control group. <h3>Disclosure of Interest</h3> None declared
Chronic Stress-Related Neural Activity Associates With Subclinical Cardiovascular Disease in Psoriasis
Authors: Aditya Goyal, Amit K. Dey, Abhishek Chaturvedi, Youssef A. Elnabawi, Tsion M. Aberra, Jonathan H. Chung, Agastya D. Belur, Jacob W. Groenendyk, Joseph B. Lerman, Joshua P. Rivers, Justin A. Rodante, Charlotte L. Harrington, Nevin J. Varghese, Gregory E. Sanda, Yvonne Baumer, Alexander V. Sorokin, Heather L. Teague, Leonard D. Genovese, Balaji Natarajan, Aditya A. Joshi, Martin P. Playford, David A. Bluemke, Marcus Y. Chen, Abass Alavi, Roger K. Pitman, Tiffany M. Powell-Wiley, Ahmed Tawakol, Joel M. Gelfand, Nehal N. Mehta
Journal: JACC. Cardiovascular imaging (2018)
A multiorgan donor cancer screening protocol: The Italian Emilia-Romagna region five year experience.
Authors: Michelangelo Fiorentino, Antonia D’errico Grigioni, Lorenza Ridolfi, Annalisa Altimari, Walter F. Grigioni
Journal: Cancer Research (2006)

5321  Background: The progressive extension of the multiorgan donor pool to elderly subjects because of organ shortage may increase the incidence of neoplastic diseases, with potential transmission to the immunosuppressed recipients. Although transplant-related cancer transmission is considered uncommon, many cases have been reported with lethal sequels. In 2001 we designed in the Emilia-Romagna region (4,000,000 inhabitants) a multiorgan donor cancer screening protocol that was adopted in 2002 by the Italian National Transplant Center. The protocol is based on a 24 hour multidisciplinary call service covering 21 main regional intensive care units, a centralized pathology laboratory and a transplant coordination center. After careful anamnesis collection, all the donors presenting in the region undergo external examination, laboratory tumor tests, thorough total body ultrasound screening and surgical inspection of the internal organs. All the suspect findings are investigated by extemporary frozen section examination. Based on the pathological findings, donors are classified according to the risk of neoplastic transmission as: (1) standard risk (no malignancy, donation is allowed), (2) non standard risk (low malignant potential tumors, donation of life-saving organs is permitted in case of clinical emergency) and (3) unacceptable risk (malignant tumors, donation is stopped). Results: In 5 years of application (2001-2005) the protocol was implemented for 767 donors. Clinical suspicion of cancer was raised in 149 (19%) donors (mean age 63±15 years, range 9-89 years) and 188 lesions were evaluated. Histological extemporary evaluation led to exclusion for unacceptable risk of 21 donors (3%) due to a malignant tumor (12 prostate cancer, 2 renal cell cancer, 2 thyroid cancer, 3 B-cell lymphomas, 1 lung cancer, 1 skin melanoma). In 3 cases (2 papillary renal neoplasms and 1 bowel GIST) donation was allowed for clinical emergencies (non standard risk). Eight donors were excluded for non neoplastic reasons (infectious diseases, organ quality). The recovery of the remaining 117 donors, _all with inflammatory or benign neoplastic diseases at histology (standard risk)_ led to the safe utilization of 285 organs. Conclusions: The incidence of potentially transmissible malignant tumors is becoming an important issue in the field of organ transplantation due to the extension of the donor pool to elderly subjects. Our screening protocol largely rules out clinically raised suspect of cancer in organ donors. Its implementation can be of great help for the rational use of marginal donors while maximizing donation safety.
Abstract 15047: Prognostic Impacts of Plasma Levels of Cyclophilin A in Patients With Heart Failure
Authors: Tomohiro Ohtsuki, Kimio Satoh, Toru Shimizu, Shohei Ikeda, Nobuhiro Yaoita, Taijyu Satoh, Junichi Omura, Nobuhiro Kikuchi, Ryo Kurosawa, Shinichiro Sunamura, Masamichi Nogi, Koichiro Sugimura, Tatsuo Aoki, Shunsuke Tatebe, Satoshi Miyata, Hiroaki Shimokawa
Journal: Circulation (2017)

BackGround: Cyclophilin A (CyPA) is secreted from cardiac fibroblasts in response to angiotensin II or mechanical stretch and promotes cardiac hypertrophy, fibrosis and the development of arteriosc...
Proteomic and phosphor-proteomic signatures of clinical hepatitis B virus-associated hepatocellular carcinoma
Authors: Chen Li, Jie Dai, Hong Ruan, Kang Tu, Ye Tan, Hong Wang, Yi Li, Jia Wu, Rong Zeng
Journal: Cancer Research (2007)

2237  We performed proteomic studies on ten pairs of clinical hepatitis B virus-associated hepatocellular carcinoma (B-type HCC) tissue samples by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) followed by one-dimensional liquid chromatography tandem mass spectrometry. Significant differentially expressed protein spots between tumorous tissues and adjacent paired nontumorous tissues were unambiguously quantitated and further analyzed by hierarchical clustering analysis and best-first search algorithm. We found that hierarchical clustering analysis divided tumorous or nontumorous groups according to their differential proteomic profiles. Best-first analysis selected the informative spots for the HCC/non-HCC classification with post-translational modifications (PTMs) in them. Western blotting further validated two differential expressed proteins with PTM isoforms among the informative spots. On the other hand, the differential expressed phosphor-proteome for HCC and non-HCC tissues was established by online 2D-LC-MS/MS based on strong anion exchanger (SAX) coupled with linear ion trap/orbitrap mass spectrometer (LTQ-Orbitrap). The phosphorylation features can also significantly contribute to differentiate the normal and disease tissues. These proteomic and phosphor-proteomic signatures associated with B-type HCC could provide personalized information of protein expression as well as post-translational modification, which will facilitate the classification of HCC, screening of useful molecular markers and give clues to elucidate the mechanism of carcinogenesis.
Abstract 19637: Intravascular Vagal Nerve Stimulation in Acute Myocardial Infarction Strikingly Improves Cardiac Function and Reduces Infarct Size in the Long-Term Despite Delaying Coronary Reperfusion
Authors: Genya Sunagawa, Keita Saku, Takahiro Arimura, Takuya Kishi, Hiroyuki Tsutsui, Kenji Sunagawa
Journal: Circulation (2017)

Introduction: In acute myocardial infarction (AMI), the extent of unsalvaged myocardium determines the progression to heart failure in the long-term. Therefore, reducing the unsalvaged myocardium is essential to prevent chronic heart failure. Recently we developed a transvenous intravascular vagal nerve stimulation (iVNS) and demonstrated that in a dog of 180 min ischemia/60 min reperfusion model, iVNS started 90 min after the onset of ischemia strikingly reduced infarct size by 61%, and prevented heart failure (HF). However, the question remains what if the ischemia already lasted for 180 min. Does iVNS remain effective over simple reperfusion? Thus we examined if iVNS 180 min after the onset of ischemia overperforms simple reperfusion in reducing infarct size and preventing HF in the long-term. Methods: In 13 mongrel dogs, we occluded the left anterior descending coronary artery (LAD) to create ischemia. In Control (n=6), 180 minutes of LAD occlusion was followed by 60 minutes of reperfusion. In delayed...
Rescue of recurrent deep intronic mutation underlying cell type–dependent quantitative NEMO deficiency
Authors: Bertrand Boisson, Yoshitaka Honda, Masahiko Ajiro, Jacinta Bustamante, Matthieu Bendavid, Andrew R. Gennery, Yuri Kawasaki, Jose Ichishima, Mitsujiro Osawa, Hiroshi Nihira, Takeshi Shiba, Takayuki Tanaka, Maya Chrabieh, Benedetta Bigio, Hong Hur, Yuval Itan, Yupu Liang, Satoshi Okada, Kazushi Izawa, Ryuta Nishikomori, Osamu Ohara, Toshio Heike, Laurent Abel, Anne Puel, Megumu K. Saito, Jean-Laurent Casanova, Masatoshi Hagiwara, Takahiro Yasumi
Journal: Journal of Clinical Investigation (2018)

X-linked dominant incontinentia pigmenti (IP) and X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) are caused by loss-of-function and hypomorphic IKBKG (also known as NEMO) mutations, respectively. We describe a European mother with mild IP and a Japanese mother without IP, whose 3 boys with EDA-ID died from ID. We identify the same private variant in an intron of IKBKG, IVS4+866 C>T, which was inherited from and occurred de novo in the European mother and Japanese mother, respectively. This mutation creates a new splicing donor site, giving rise to a 44-nucleotide pseudoexon (PE) generating a frameshift. Its leakiness accounts for NF-κB activation being impaired but not abolished in the boys' cells. However, aberrant splicing rates differ between cell types, with WT NEMO mRNA and protein levels ranging from barely detectable in leukocytes to residual amounts in induced pluripotent stem cell-derived (iPSC-derived) macrophages, and higher levels in fibroblasts and iPSC-derived neuronal precursor cells. Finally, SRSF6 binds to the PE, facilitating its inclusion. Moreover, SRSF6 knockdown or CLK inhibition restores WT NEMO expression and function in mutant cells. A recurrent deep intronic splicing mutation in IKBKG underlies a purely quantitative NEMO defect in males that is most severe in leukocytes and can be rescued by the inhibition of SRSF6 or CLK.
Genome wide association study of hepatitis C virus- and cryoglobulin-related vasculitis
Authors: A L Zignego, G L Wojcik, P Cacoub, M Visentini, M Fiorilli, B Terrier, A Mangia, R Latanich, E Charles, S I Khakoo, M P Busch, L B Dustin, D L Thomas, P Duggal
Journal: Hepatology (2013)
Analysis of RET rearrangement in non-small cell lung cancer cell blocks from pleural effusion
Authors: C. Xu, W.-X. Wang, Q.-X. Zhang, W. Zhuang, Y.-W. Tian, J.-P. Xu, M.-Y. Fang, Y.-P. Chen, G. Chen, T.-F. Lv, Y. Song
Journal: Annals of Oncology (2018)
Optimizing Cardiovascular Care in Children With Acute Myeloid Leukemia to Improve Cancer-Related Outcomes
Authors: Saro H. Armenian, Matthew J. Ehrhardt
Journal: Journal of Clinical Oncology (2018)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 14-year-old African American female presented with fatigue, easy bruising, and fever. On examination, she had scattered bruising, lymphadenopathy, and hepatosplenomegaly. Laboratory evaluation revealed pancytopenia with peripheral blasts, and acute myeloid leukemia (AML; French-American-British M2, t[8;21][q22;q22.1]) was diagnosed on bone marrow biopsy. A baseline echocardiogram revealed normal left ventricular (LV) systolic function (ejection fraction [EF], 60%; shortening fraction [SF], 32%), and conventional chemotherapy was initiated that consisted of two cycles of remission induction (cytarabine, etoposide, and daunorubicin [50 mg/m 2 × 3 days per cycle]) followed by intensification 1 (high-dose cytarabine and etoposide), intensification 2 (high-dose cytarabine and mitoxantrone [12 mg/m 2 /dose daily; four total doses]), and intensification 3 (high-dose cytarabine and l-asparaginase). Of note, an echocardiogram was not repeated before the start of intensification 1. During intensification 1, the patient developed Streptococcus viridans sepsis, which required 4 days in the intensive care unit with antimicrobial and inotropic support. Repeat echocardiogram after recovery from the sepsis episode demonstrated low-normal LV systolic function (EF, 53%; SF, 27%), and she subsequently began intensification 2. On day 3 of intensification 2, the patient developed afebrile tachypnea, tachycardia, and an increasing oxygen requirement. Chest x-ray revealed cardiomegaly and pulmonary vascular congestion. Cardiac troponins were normal, whereas N-terminal pro B-type natriuretic peptide was 10 times the upper limit of normal. Repeat echocardiogram showed an enlarged LV with moderate to severely depressed LV function (EF, 28%; SF, 14%). Day 4 mitoxantrone was omitted and a cardiology consult obtained.
CD3+CD4−CD8− mucosal T cells are associated with uncontrolled chronic rhinosinusitis with nasal polyps
Authors: Tanja Kosak Soklic, Mira Silar, Matija Rijavec, Ana Koren, Izidor Kern, Irena Hocevar-Boltezar, Peter Korosec
Journal: Journal of Allergy and Clinical Immunology (2018)
Posttranslational Modifications of PD-L1 and Their Applications in Cancer Therapy
Authors: Jung-Mao Hsu, Chia-Wei Li, Yun-Ju Lai, Mien-Chie Hung
Journal: Cancer Research (2018)

Abstract Posttranslational modifications (PTM) of PD-L1 have emerged as important regulatory mechanisms that modulate immunosuppression in patients with cancer. In exposure to inflammatory cytokines, cancer cells and antigen-presenting cells, such as macrophages and dendritic cells, express PD-L1 to inhibit the activity of effector T cells through PD-1 engagement. Recent studies suggested that glycosylation, phosphorylation, ubiquitination, sumoylation, and acetylation play important roles in the regulation of PD-L1 protein stability and translocation and protein–protein interactions. Aberrant alterations of PTMs directly influence PD-L1–mediated immune resistance. On the basis of the newly identified regulatory signaling pathways of PD-L1 PTMs, researchers have investigated the cancer therapeutic potential of natural food compounds, small-molecule inhibitors, and mAbs by targeting PD-L1 PTMs. Results of these preclinical studies demonstrated that targeting PTMs of PD-L1 yields promising antitumor effects and that clinical translation of these therapeutic strategies is warranted. Cancer Res; 78(22); 6349–53. ©2018 AACR.