tbuckley/cabot-search huggingface dataset:
Lung Ultrasound and Pulmonary Congestion During Stress Echocardiography
Authors: Maria Chiara Scali, Angela Zagatina, Quirino Ciampi, Lauro Cortigiani, Antonello D'Andrea, Clarissa Borguezan Daros, Nadezhda Zhuravskaya, Jaroslaw D. Kasprzak, Karina Wierzbowska-Drabik, José Luis de Castro e Silva Pretto, Ana Djordjevic-Dikic, Branko Beleslin, Marija Petrovic, Nikola Boskovic, Milorad Tesic, Ines Monte, Iana Simova, Martina Vladova, Alla Boshchenko, Alexander Vrublevsky, Rodolfo Citro, Miguel Amor, Paul E. Vargas Mieles, Rosina Arbucci, Pablo Martin Merlo, Diego M. Lowenstein Haber, Claudio Dodi, Fausto Rigo, Suzana Gligorova, Milica Dekleva, Sergio Severino, Fabio Lattanzi, Doralisa Morrone, Maurizio Galderisi, Marco A.R. Torres, Alessandro Salustri, Hugo Rodrìguez-Zanella, Fabio Marco Costantino, Albert Varga, Gergely Agoston, Eduardo Bossone, Francesco Ferrara, Nicola Gaibazzi, Jelena Celutkiene, Maciej Haberka, Fabio Mori, Maria Grazia D'Alfonso, Barbara Reisenhofer, Ana Cristina Camarozano, Marcelo Haertel Miglioranza, Ewa Szymczyk, Paulina Wejner-Mik, Katarzyna Wdowiak-Okrojek, Tamara Preradovic-Kovacevic, Tonino Bombardini, Miodrag Ostojic, Aleksandra Nikolic, Federica Re, Andrea Barbieri, Giovanni Di Salvo, Elisa Merli, Paolo Colonna, Valentina Lorenzoni, Michele De Nes, Marco Paterni, Clara Carpeggiani, Jorge Lowenstein, Eugenio Picano
Journal: JACC. Cardiovascular imaging (2020)
RNA Identification of PRIME Cells Predicting Rheumatoid Arthritis Flares
Authors: Dana E. Orange, Vicky Yao, Kirsty Sawicka, John Fak, Mayu O. Frank, Salina Parveen, Nathalie E. Blachere, Caryn Hale, Fan Zhang, Soumya Raychaudhuri, Olga G. Troyanskaya, Robert B. Darnell
Journal: New England Journal of Medicine (2020)

Rheumatoid arthritis, like many inflammatory diseases, is characterized by episodes of quiescence and exacerbation (flares). The molecular events leading to flares are unknown.
Hypoxia and oxidative stress induce VLA-4-dependent melanoma cell adhesion to endothelial cells via IL-18-dependent TNFalpha production from tumor cells under NF-kB control mechanism
Authors: Naiara Telleria, Teresa Carrascal, Maria Valcarcel, Natalia Gallot, Lorea Mendoza, Fernando Vidal-Vanaclocha
Journal: Cancer Research (2004)

4906  Interleukin-18 (IL-18) is a member of IL-1 family that plays an important role in the host defense and has been proposed as adjuvant therapy against cancer. However, IL-18 production has also been detected in the tumor microenvironment, and, therefore, whether or not IL-18 is an useful tool against cancer progression is unclear. Culture of B16 melanoma (B16M) cells for 18 hours under an hypoxic atmosphere that mimics tumor microenvironment increased their hepatic metastasis efficiency and their adhesion to sinusoidal endotelial cells. Hypoxic environment also increased IL-18 receptor-alpha (IL-18Ralpha)-expressing B16M cell number by 5-fold as compared to normoxic controls (from 5.2% to 24%). IL-18 and IL-18Ralpha gene transcription increased by 2-fold in glutathione (GSH)-depleted B16M cells —l-buthionine (S,R)-sulfoximine-pretreated— given 10 μM hydrogen peroxide for 6 hours, as shown by quantitative RT-PCR. Recombinant IL-18-treated low-GSH content B16M cells —from in vitro cell growth at confluency— increased their adhesion to endotelial cells in a dose- and time-dependent manner. This proadhesive response was abrogated in B16M cells given N-acetylcysteine prior to IL-18. Adhesion to endotelial cell did not vary in IL-18-treated high GSH-content B16M cells —from in vitro exponentially growing cells—; however it increased when exponentially growing B16M cells were BSO-pretreated to deplete GSH prior to IL-18 addition. TNF binding protein (TNFbp) and anti-mouse alpha4 integrin antibodies abolished adhesion-stimulating effect of IL-18 on B16M. alpha4 integrin mRNA increased in IL-18-treated B16M cells. However, TNFbp inhibited IL-18-induced alpha4 integrin expression. TNFalpha and TNF-R1 gene transcription also increased by 2-fold in B16M cells cultured under oxidative stress conditions. Moreover, intracellular TNFalpha-expressing cell number increased by 2-fold in IL-18-treated B16M cells as compared to controls (from 28% to 55%). NF-kappaB translocation occurred in IL-18-treated B16M, as shown by electrophoretic mobility gel shift asssay and anti-p65 NF-kappaB antibody; and both proteasome inhibitor MG-132 and catalase abrogated IL-18-dependent TNFalpha production from B16M cells and their adhesion to endothelium. It has been reported that VLA-4 downregulation promotes melanoma cell dissemination. Current results demonstrate that hypoxia and oxidative stress increase melanoma cell responsiveness to IL-18 and TNFalpha. The mechanism is potentiated by a concomitant IL-18-dependent TNFalpha production from B16M cells under NF-kappaB control mechanism. This microenvironmental modulation leads to VLA-4-dependent melanoma cell adhesion to endothelium. In turn, it may account for intravascular arrest and metastatic progression of circulating melanoma cells.
Chitosan hydrogel incorporated with dental pulp stem cell-derived exosomes alleviates periodontitis in mice via a macrophage-dependent mechanism
Authors: Zongshan Shen, Shuhong Kuang, Yong Zhang, Mingmei Yang, Wei Qin, Xuetao Shi, Zhengmei Lin
Journal: Bioactive Materials (2020)

Periodontitis is caused by host immune-inflammatory response to bacterial insult. A high proportion of pro-inflammatory macrophages to anti-inflammatory macrophages leads to the pathogenesis of periodontitis. As stem cell-derived exosomes can modulate macrophage phenotype, dental pulp stem cell-derived exosomes (DPSC-Exo) can effectively treat periodontitis. In this study, we demonstrated that DPSC-Exo-incorporated chitosan hydrogel (DPSC-Exo/CS) can accelerate the healing of alveolar bone and the periodontal epithelium in mice with periodontitis. Gene Ontology (GO) term enrichment analysis showed that treatment with DPSC-Exo/CS ameliorated periodontal lesion by suppressing periodontal inflammation and modulating the immune response. Specifically, DPSC-Exo/CS facilitated macrophages to convert from a pro-inflammatory phenotype to an anti-inflammatory phenotype in the periodontium of mice with periodontitis, the mechanism of which could be associated with miR-1246 in DPSC-Exo. These results not only shed light on the therapeutic mechanism of DPSC-Exo/CS but also provide the basis for developing an effective therapeutic approach for periodontitis.
Update: Clostridium novyi and unexplained illness among injecting-drug users - Scotland, Ireland, and England, April-June 2000.
Authors: S. Ahmed, L. Gruer, G. McGuigan, G. Penrice, K. Roberts, J. Hood, P. Redding, G. Edwards, M. Black, J. McFarlane, D. Cromie, H. Howie, A. Leonard, D. Goldberg, A. Taylor, S. Hutchinson, K. Roy, S. Wadd, R. Andraghetti, J. Barry, G. Sayers, M. Cronin, T. O'Connell, M. Ward, P. O'Sullivan, B. O'Herlihy
Journal: MMWR Morbidity and Mortality Weekly Report (2000)
Gallbladder Visualization in Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE
Authors: Johanna Diekmann, Rudolf A. Werner, Tobias L. Ross, Thorsten Derlin
Journal: Clinical Nuclear Medicine (2020)

Gallbladder visualization represents a rare incidental finding when using somatostatin receptor-targeted SPECT radiopharmaceuticals such as In-octreotide. We present the case of a 30-year-old man with pseudomyogenic hemangioendothelioma who underwent Ga-DOTATATE PET/CT for restaging of metastatic disease and subsequent treatment with peptide receptor radionuclide therapy with Lu-DOTATATE. Posttherapeutic SPECT/CT, but not pretherapeutic or posttherapeutic PET/CT, showed gallbladder visualization, evidencing Lu-DOTATATE excretion into the bile. This case highlights that biliary Lu-DOTATATE excretion may represent a rare mimicker of hepatic metastases and emphasizes the role SPECT/CT for precise anatomical correlation to avoid misinterpretation.
SPARC enables genetic manipulation of precise proportions of cells
Authors: Jesse Isaacman-Beck, Kristine C. Paik, Carl F. R. Wienecke, Helen H. Yang, Yvette E. Fisher, Irving E. Wang, Itzel G. Ishida, Gaby Maimon, Rachel I. Wilson, Thomas R. Clandinin
Journal: Nature Neuroscience (2020)
An Integrated Multi-omic Single-Cell Atlas of Human B Cell Identity
Authors: David R. Glass, Albert G. Tsai, John Paul Oliveria, Felix J. Hartmann, Samuel C. Kimmey, Ariel A. Calderon, Luciene Borges, Marla C. Glass, Lisa E. Wagar, Mark M. Davis, Sean C. Bendall
Journal: Immunity (2020)

B cells are capable of a wide range of effector functions including antibody secretion, antigen presentation, cytokine production, and generation of immunological memory. A consistent strategy for classifying human B cells by using surface molecules is essential to harness this functional diversity for clinical translation. We developed a highly multiplexed screen to quantify the co-expression of 351 surface molecules on millions of human B cells. We identified differentially expressed molecules and aligned their variance with isotype usage, VDJ sequence, metabolic profile, biosynthesis activity, and signaling response. Based on these analyses, we propose a classification scheme to segregate B cells from four lymphoid tissues into twelve unique subsets, including a CD45RB+CD27- early memory population, a class-switched CD39+ tonsil-resident population, and a CD19hiCD11c+ memory population that potently responds to immune activation. This classification framework and underlying datasets provide a resource for further investigations of human B cell identity and function.
5-FU, Irinotecan, Nab-Paclitaxel in Gastrointestinal Cancers—Letter
Authors: Osamu Maeda, Tomoya Shimokata, Yuichi Ando
Journal: Clinical Cancer Research (2020)

In the safety and tolerability study of a novel FOLFIRABRAX regimen in patients with gastrointestinal cancers by Joshi and colleagues (1), the irinotecan doses were determined by UGT1A1 genotypes: 180, 135, and 90 for wild-type (*1/*1), heterozygous (*1/*28), and homozygous (*28/*28) patients, respectively. The authors reported that this regimen with genotype-guided dosing of irinotecan was tolerable based on the result that dose-limiting toxicities occurred in 5 of 23 (22%) wild-type, 1 of 19 (5%) heterozygous, and 0 of 7 homozygous patients. However, their conclusion truly concerns us that the regimen is not strong enough for patients with any of the genotypes. According to the genotype-guided dose-finding studies of irinotecan in analogous FOLFIRI regimens, the maximum-tolerated or recommended doses for wild-type and heterozygous patients were more than 300 mg/m2 and that for homozygous patients was 130 mg/m2 (2, 3). The irinotecan doses used in the FOLFIRABRAX regimen are clearly too low. It is of our opinion that the standard one-size dose of biweekly irinotecan, regardless of UGT1A1 genotype, should be tailored to at least 300 mg/m2 or more for wild-type and heterozygous patients, and 120–150 mg/m2 would be appropriate for homozygous patients, which corresponds to a 1 or 2 dose level reduction compared with that in the package insert of the drug. This dosing is consistent with the finding of the previous pharmacokinetic study that the exposure to the active metabolite SN-38 is approximately double in homozygous patients compared with patients with the other genotypes. The real benefit of genotype-guided dosing of irinotecan is not only to avoid unnecessary toxicity of irinotecan in homozygous patients by reducing the dose but also to enhance the therapeutic efficacy in wild-type and heterozygous patients by increasing the dose to the optimal one.See the Response, p. 3890O. Maeda reports receiving speakers bureau honoraria from Yakult Honsha Co., Ltd. and Taiho Pharmaceutical Co., Ltd. Y. Ando reports receiving commercial research grants from Yakult Honsha, Mochida Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo, and Nippon Kayaku, and reports receiving speakers bureau honoraria from Yakult Honsha, Taiho Pharmaceutical, Daiichi Sankyo, and Sawai Pharmaceutical. No potential conflicts of interest were disclosed by the other author.
Efficacy and safety of bempedoic acid for the treatment of hypercholesterolemia: A systematic review and meta-analysis
Authors: Arrigo F. G. Cicero, Federica Fogacci, Adrian V. Hernandez, Maciej Banach
Journal: PLoS Medicine (2020)

Background Bempedoic acid is a first-in-class lipid-lowering drug recommended by guidelines for the treatment of hypercholesterolemia. Our objective was to estimate its average effect on plasma lipids in humans and its safety profile. Methods and findings We carried out a systematic review and meta-analysis of phase II and III randomized controlled trials on bempedoic acid (PROSPERO: CRD42019129687). PubMed (Medline), Scopus, Google Scholar, and Web of Science databases were searched, with no language restriction, from inception to 5 August 2019. We included 10 RCTs (n = 3,788) comprising 26 arms (active arm [n = 2,460]; control arm [n = 1,328]). Effect sizes for changes in lipids and high-sensitivity C-reactive protein (hsCRP) serum concentration were expressed as mean differences (MDs) and 95% confidence intervals (CIs). For safety analyses, odds ratios (ORs) and 95% CIs were calculated using the Mantel–Haenszel method. Bempedoic acid significantly reduced total cholesterol (MD −14.94%; 95% CI −17.31%, −12.57%; p < 0.001), non-high-density lipoprotein cholesterol (MD −18.17%; 95% CI −21.14%, −15.19%; p < 0.001), low-density lipoprotein cholesterol (MD −22.94%; 95% CI −26.63%, −19.25%; p < 0.001), low-density lipoprotein particle number (MD −20.67%; 95% CI −23.84%, −17.48%; p < 0.001), apolipoprotein B (MD −15.18%; 95% CI −17.41%, −12.95%; p < 0.001), high-density lipoprotein cholesterol (MD −5.83%; 95% CI −6.14%, −5.52%; p < 0.001), high-density lipoprotein particle number (MD −3.21%; 95% CI −6.40%, −0.02%; p = 0.049), and hsCRP (MD −27.03%; 95% CI −31.42%, −22.64%; p < 0.001). Bempedoic acid did not significantly modify triglyceride level (MD −1.51%; 95% CI −3.75%, 0.74%; p = 0.189), very-low-density lipoprotein particle number (MD 3.79%; 95% CI −9.81%, 17.39%; p = 0.585), and apolipoprotein A-1 (MD −1.83%; 95% CI −5.23%, 1.56%; p = 0.290). Treatment with bempedoic acid was positively associated with an increased risk of discontinuation of treatment (OR 1.37; 95% CI 1.06, 1.76; p = 0.015), elevated serum uric acid (OR 3.55; 95% CI 1.03, 12.27; p = 0.045), elevated liver enzymes (OR 4.28; 95% CI 1.34, 13.71; p = 0.014), and elevated creatine kinase (OR 3.79; 95% CI 1.06, 13.51; p = 0.04), though it was strongly associated with a decreased risk of new onset or worsening diabetes (OR 0.59; 95% CI 0.39, 0.90; p = 0.01). The main limitation of this meta-analysis is related to the relatively small number of individuals involved in the studies, which were often short or middle term in length. Conclusions Our results show that bempedoic acid has favorable effects on lipid profile and hsCRP levels and an acceptable safety profile. Further well-designed studies are needed to explore its longer-term safety.
Abstract 15833: C-Reactive Protein Increases Tissue Factor Expression and Promotes Thrombosis in Vein Bypass Grafts
Authors: Yan Ji, Tammy L Strawn, Alexander J Szalai, William P Fay
Journal: Circulation (2013)

Background: Increased expression of C-reactive protein (CRP) is associated with early occlusion of vein bypass grafts (VGs), a major clinical problem in which thrombosis plays a key role. In vitro ...
Comparison of Atrial Remodeling Caused by Sustained Atrial Flutter Versus Atrial Fibrillation
Authors: Jean-Baptiste Guichard, Patrice Naud, Feng Xiong, Xiaoyan Qi, Nathalie L’Heureux, Roddy Hiram, Jean-Claude Tardif, Raymond Cartier, Antoine Da Costa, Stanley Nattel
Journal: Journal of the American College of Cardiology (2020)
Editor's Note: Role of CAAT/Enhancer Binding Protein Homologous Protein in Panobinostat-mediated Potentiation of Bortezomib-induced Lethal Endoplasmic Reticulum Stress in Mantle Cell Lymphoma Cells
Authors: Rekha Rao, Srilatha Nalluri, Warren Fiskus, Andrew Savoie, Kathleen M. Buckley, Kyungsoo Ha, Ramesh Balusu, Atul Joshi, Veena Coothankandaswamy, Jianguo Tao, Eduardo Sotomayor, Peter Atadja, Kapil N. Bhalla
Journal: Clinical Cancer Research (2020)
Correspondence on ‘Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study‘
Authors: Maria De Santis, Antonio Voza, Victor Savevski, Salvatore Badalamenti, Maurizio Cecconi, Alberto Mantovani, Carlo Selmi
Journal: Annals of the Rheumatic Diseases (2021)

Objectives  To prospectively investigate in patients with severe COVID-19-associated cytokine storm syndrome (CSS) whether an intensive course of glucocorticoids with or without tocilizumab accelerates clinical improvement, reduces mortality and prevents invasive mechanical ventilation, in comparison with a historic control group of patients who received supportive care only.  Methods  From 1 April 2020, patients with COVID-19-associated CSS, defined as rapid respiratory deterioration plus at least two out of three biomarkers with important elevations (C-reactive protein >100 mg/L; ferritin >900 µg/L; D-dimer >1500 µg/L), received high-dose intravenous methylprednisolone for 5 consecutive days (250 mg on day 1 followed by 80 mg on days 2–5). If the respiratory condition had not improved sufficiently (in 43%), the interleukin-6 receptor blocker tocilizumab (8 mg/kg body weight, single infusion) was added on or after day 2. Control patients with COVID-19-associated CSS (same definition) were retrospectively sampled from the pool of patients (n=350) admitted between 7 March and 31 March, and matched one to one to treated patients on sex and age. The primary outcome was ≥2 stages of improvement on a 7-item WHO-endorsed scale for trials in patients with severe influenza pneumonia, or discharge from the hospital. Secondary outcomes were hospital mortality and mechanical ventilation.  Results  At baseline all patients with COVID-19 in the treatment group (n=86) and control group (n=86) had symptoms of CSS and faced acute respiratory failure. Treated patients had 79% higher likelihood on reaching the primary outcome (HR: 1.8; 95% CI 1.2 to 2.7) (7 days earlier), 65% less mortality (HR: 0.35; 95% CI 0.19 to 0.65) and 71% less invasive mechanical ventilation (HR: 0.29; 95% CI 0.14 to 0.65). Treatment effects remained constant in confounding and sensitivity analyses.  Conclusions  A strategy involving a course of high-dose methylprednisolone, followed by tocilizumab if needed, may accelerate respiratory recovery, lower hospital mortality and reduce the likelihood of invasive mechanical ventilation in COVID-19-associated CSS.
Chemotherapy can induce breakage in the FRA12E/SMRT fragile site.
Authors: Christiane Houde, Jean Dolce, Heather Foreman, Lionel Coignet
Journal: Cancer Research (2007)

4768  Background: The Silencing Mediator of Retinoic Acid and Thyroid Hormone Receptor (SMRT) gene  that maps at chromosome 12q24 is a transcriptional co-repressor. We recently determined that various cancer cell lines and samples from cancer patients with solid tumors that developed advanced disease have altered SMRT expression. In addition, we mapped a fragile site (FRA12E) within the SMRT gene. Pilot studies indicated that patients with metastatic disease have a higher incidence of FRA12E in their genome.  Hypothesis: Based on the fact that aphidicolin (the fragile site inducer used in vitro) as well as Doxorubycin/ Adriamycin are DNA polymerase inhibitors, we tested the hypothesis that Doxorubycin/Adriamycin-based chemotherapy could induce breakage at the FRA12E fragile site in carriers9 genome.  Material and Methods: We identified two lymphoblastoid cell lines that are carriers and non-carriers of the FRA12E/SMRT fragile site, respectively. Their carrier status was established using our FISH approach: each cell line was cultured in the presence of aphidicolin (an inducer of fragile sites); chromosomes were harvested and fixed using classical cytogenetic techniques. SMRT-specific BAC clones were used in fluorescence in-situ hybridization (FISH) experiments using each cell line’s metaphase chromosomes. Metaphase images were collected, scored, and analyzed for a disrupted FISH signal indicative of FRA12E presence. Following the same procedure, DOX/ADR was tested at sub-optimal concentrations for its fragile site induction potential in both carrier and non-carrier lymphoblastoid cell lines.  Results: The results of this study showed that a sub-optimal concentration of 0.01 uM of DOX is able to induce the breakage of the FRA12E/SMRT fragile site in the carrier cell line only. The results obtained with this DOX dosage were highly comparable with those obtained with aphidicolin.  Discussion: This study examined the potential FRA12E/SMRT fragile site induction by DOX/ADR in the context of a carrier genome. We were able to demonstrate that a sub-optimal dose of Adryamycin is able to recapitulate the effect of the aphidicolin used in vitro to demonstrate the presence of a fragile site. This is of particular importance since we have shown that the presence of the FRA12E fragile site in a cancer patient’s genome has a high predictive value for development of metastasis. Additional studies are ongoing, especially testing additional chemotherapy drugs used in treatment regimen.
Glucocorticoid-induced eosinopenia results from CXCR4-dependent bone marrow migration
Authors: So Gun Hong, Noriko Sato, Fanny Legrand, Manasi Gadkari, Michelle Makiya, Kindra Stokes, Katherine N. Howe, Shiqin Judy Yu, Nathaniel Seth Linde, Randall R. Clevenger, Timothy Hunt, Zonghui Hu, Peter L. Choyke, Cynthia E. Dunbar, Amy D. Klion, Luis M. Franco
Journal: Blood (2020)
Glecaprevir–pibrentasvir to treat chronic hepatitis C virus infection in Asia: two multicentre, phase 3 studies—a randomised, double-blind study (VOYAGE-1) and an open-label, single-arm study (VOYAGE-2)
Authors: Lai Wei, Guiqiang Wang, Negar N Alami, Wen Xie, Jeong Heo, Qing Xie, Mingxiang Zhang, Yoon Jun Kim, Seng Gee Lim, Linda M Fredrick, Wenjing Lu, Wei Liu, Hari V Kalluri, Preethi Krishnan, Rakesh Tripathi, Niloufar Mobashery, Margaret Burroughs, Armen Asatryan, Jidong Jia, Jinlin Hou
Journal: The Lancet. Gastroenterology & hepatology (2020)
Abstract 12526: Understanding Palliative Care Preferences Among Adults With Congenital Heart Disease
Authors: Jill M Steiner, Karen K Stout, James N Kirkpatrick, J Randall Curtis
Journal: Circulation (2018)

Background: Maximizing quality of life and honoring care preferences are at the forefront of high-quality care for patients with adult congenital heart disease (ACHD). Palliative care (PC) and adva...