tbuckley/cabot-search huggingface dataset:
<i>Pseudomonas aeruginosa</i>adaptation and diversification in the non-cystic fibrosis bronchiectasis lung
Authors: Yasmin Hilliam, Matthew P. Moore, Iain L. Lamont, Diana Bilton, Charles S. Haworth, Juliet Foweraker, Martin J. Walshaw, David Williams, Joanne L. Fothergill, Anthony De Soyza, Craig Winstanley
Journal: European Respiratory Journal (2017)

To characterise Pseudomonas aeruginosa populations during chronic lung infections of non-cystic fibrosis bronchiectasis patients, we used whole-genome sequencing to 1) assess the diversity of P. aeruginosa and the prevalence of multilineage infections; 2) seek evidence for cross-infection or common source acquisition; and 3) characterise P. aeruginosa adaptations. 189 isolates, obtained from the sputa of 91 patients attending 16 adult bronchiectasis centres in the UK, were whole-genome sequenced. Bronchiectasis isolates were representative of the wider P. aeruginosa population. Of 24 patients from whom multiple isolates were examined, there were seven examples of multilineage infections, probably arising from multiple infection events. The number of nucleotide variants between genomes of isolates from different patients was in some cases similar to the variations observed between isolates from individual patients, implying the possible occurrence of cross-infection or common source acquisition. Our data indicate that during infections of bronchiectasis patients, P. aeruginosa populations adapt by accumulating loss-of-function mutations, leading to changes in phenotypes including different modes of iron acquisition and variations in biofilm-associated polysaccharides. The within-population diversification suggests that larger scale longitudinal surveillance studies will be required to capture cross-infection or common source acquisition events at an early stage.
Cyclosporine in severe ulcerative colitis: Predictors of response
Authors: G Cullen, D Keegan, S Verma, H Mulcahy, D O'Donoghue
Journal: Endoscopy (2005)

Cyclosporin (CsA) will induce a remission in severe steroid resistant Ulcerative Colitis (UC) in 65% of patients. Opponents of CsA argue that this merely delays surgery and does not justify the risks.
PD-1 blockade for relapsed lymphoma post–allogeneic hematopoietic cell transplant: high response rate but frequent GVHD
Authors: Bradley M. Haverkos, Diana Abbott, Mehdi Hamadani, Philippe Armand, Mary E. Flowers, Reid Merryman, Manali Kamdar, Abraham Sebastian Kanate, Ayman Saad, Amitkumar Mehta, Siddhartha Ganguly, Timothy S. Fenske, Parameswaran Hari, Robert Lowsky, Leslie Andritsos, Madan Jagasia, Asad Bashey, Stacey Brown, Veronika Bachanova, Deborah Stephens, Shin Mineishi, Ryotaro Nakamura, Yi-Bin Chen, Bruce R. Blazar, Jonathan Gutman, Steven M. Devine
Journal: Blood (2017)
Assessing environmental health risks.
Authors: Misch A, Satoh T, McCally M, de Sa P, Engelman R, Jarrell J, Gocmen A, Foster W, Brant R, Chan S, Sevcik M, Odokuma Lo, Dickson Aa, Khan B, Baig Ma, Bone W, Jones Ar, Morin C, Nieschlag E, Cooper Tg, Sharma Dc
Journal: BMJ (1994)

The chemical industry has piled many chemicals on humans which cause many serious health consequences.  Research on chemical effects shows that a definite link exists between exposure to some industrial chemicals and specific serious diseases especially cancer.  For example benzene is linked to leukemia.  Recent studies indicate that increases in the incidence and mortality rate of cancers with no known links to smoking are occurring.  These increases effect the young and old alike.  Genetic factors do not account for all of the increase. Evidence that many environmental pollutants at low levels of exposure undermine biological function is growing.  This impaired functioning occurs without any obvious signs of disease.  US regulatory agencies view of chemical risks (i.e. cancer prevention) is thus incomplete. Toxic effects at lower levels of exposure are particularly worrisome since almost everyone and every plant and animal are exposed to low levels of some chemicals.  Neurotoxins (e.g. lead and solvents) cause short-term memory problems dizziness fatigue irritability inability to concentrate and structural changes to the nervous system.  The best evidence for a link between environmental pollution and immune dysfunction is asthma and respiratory illnesses.  The cause of about 60% of reproductive and development disorders is not known.  People who work with glycol ether have a high rate of adverse reproductive outcomes. These links and identified effects call for a more conservative approach to chemical regulation.  Regulatory agencies e.g. US Environmental Protection Agency need to include the growing evidence of toxic effects at lower levels into their chemical risk assessments.  Specifically their specialists must consider potential effects on the nervous system the endocrine and reproductive systems and the immune system.
Abstract 18795: Non-Vitamin K Oral Anticoagulants Are Non-Inferior for Stroke Prevention but Cause Fewer Major Bleedings Than Well-Managed Warfarin With Time in Therapeutic Range 70% or Higher in Sweden
Authors: Vilhelm Sjögren, Björn Byström, Bo Norrving, Jonas Oldgren, Henrik Renlund, Peter J Svensson, Anders Själander
Journal: Circulation (2016)

Introduction: For patients with atrial fibrillation (AF), non-vitamin K oral anticoagulants (NOACs) (dabigatran, rivaroxaban, and apixaban) have been proven non-inferior or superior to warfarin in ...
Algorithm for identification of asthma–COPD overlap: consensus between the Spanish COPD and asthma guidelines
Authors: Marc Miravitlles, Francisco Javier Alvarez-Gutierrez, Myriam Calle, Ciro Casanova, Borja G. Cosio, Antolín López-Viña, Luis Pérez de Llano, Santiago Quirce, Miguel Roman-Rodríguez, Juan José Soler-Cataluña, Vicente Plaza
Journal: European Respiratory Journal (2017)

It was as early as 1959 that the report of the CIBA Symposium described the possible coexistence of different obstructive airway diseases, such as asthma, chronic bronchitis and/or emphysema, in the same individual. However, because there were no specific therapies for all these different expressions of lung disease, these overlaps were largely ignored by guidelines. In 1995, the American Thoracic Society chronic obstructive pulmonary disease (COPD) statement included a Venn diagram with the different possible overlaps of clinical presentation of obstructive lung diseases [1], but no specific recommendations of treatment were provided for them. It was not until 2007 that the Canadian COPD guidelines specified that: "if the asthma component (in COPD) is prominent, earlier introduction of inhaled corticosteroids (ICS) may be justified" [2]. Later, in 2010, the Japanese guidelines for COPD dedicated a chapter to "Treatment of COPD complicated by asthma" [3]. To the best of our knowledge, the Spanish guidelines for COPD (GesEPOC) in 2012 were the first to propose specific criteria for the identification of the so-called asthma–COPD overlap (ACO) [4, 5]. Because there was no internationally accepted definition of ACO, a group of experts proposed diagnostic criteria for ACO in COPD [6] and these were adopted in the document. The major criteria were as follows: a very positive bronchodilator response (>400 mL and >15% increase in forced expiratory volume in 1 s (FEV1)), sputum eosinophilia or a previous diagnosis of asthma. Minor criteria were an increased total serum IgE, previous history of atopy or a positive bronchodilator test (>200 mL and >12% in FEV1) on at least two occasions [6]. To be diagnosed with ACO, a patient must fulfil two major or one major and two minor criteria. Other national guidelines for COPD, such as the Finnish [7] and the Czech guidelines [8], followed this approach and proposed similar criteria for ACO. An algorithm to identify patients with ACO rather than asthma or COPD alone <http://ow.ly/Viyy308Ehdk>
A Specific Gut Microbiota Dysbiosis of Type 2 Diabetic Mice Induces GLP-1 Resistance through an Enteric NO-Dependent and Gut-Brain Axis Mechanism
Authors: Estelle Grasset, Anthony Puel, Julie Charpentier, Xavier Collet, Jeffrey E. Christensen, François Tercé, Rémy Burcelin
Journal: Cell Metabolism (2017)
Making progress toward understanding the genetic architecture of asthma in the most affected US ethnic group
Authors: Blanca E. Himes, Victor E. Ortega
Journal: European Respiratory Journal (2017)

Asthma is a common airway disease that results from complex interactions among genetic and environmental factors. In the USA, asthma disparities by race and ethnicity are a well-known problem [1]: prevalence is highest among Puerto Ricans (16.1%), followed by non-Hispanic blacks (11.2%), non-Hispanic whites (7.7%) and Mexicans (5.4%) [2]. These disparities extend to asthma morbidity and mortality, which are highest in Puerto Ricans and African Americans compared to members of other racial/ethnic groups in the USA [3, 4]. Previous studies suggest that inter-ethnic differences in asthma risk and severity are related to differences in genetic ancestry, reflected by racial/ethnic categories [5]; however, the study of genetics in minority groups who share the largest asthma burden has lagged, compared to the study of the genetics of asthma in subjects of European ancestry [6]. Asthma GWAS of Puerto Rican individuals finds strongest association within the 17q21 ORMDL3/GSDMB locus <http://ow.ly/M23930ayVbG>
Safety and Activity of Varlilumab, a Novel and First-in-Class Agonist Anti-CD27 Antibody, in Patients With Advanced Solid Tumors
Authors: Howard A. Burris, Jeffrey R. Infante, Stephen M. Ansell, John J. Nemunaitis, Geoffrey R. Weiss, Victor M. Villalobos, Branimir I. Sikic, Matthew H. Taylor, Donald W. Northfelt, William E. Carson, Thomas R. Hawthorne, Thomas A. Davis, Michael J. Yellin, Tibor Keler, Timothy Bullock
Journal: Journal of Clinical Oncology (2017)

Purpose CD27, a costimulatory molecule on T cells, induces intracellular signals that mediate cellular activation, proliferation, effector function, and cell survival upon binding to its ligand, CD70. Varlilumab is a novel, first-in-class, agonist CD27 antibody that stimulates the CD27 pathway, which results in T-cell activation and antitumor activity in tumor models. This first-in-human, dose-escalation and expansion study evaluated the safety, pharmacology, and activity of varlilumab in patients with advanced solid tumors. Methods In a 3 + 3 dose-escalation design (n = 25), patients received a single dose of varlilumab (0.1, 0.3, 1.0, 3.0, or 10 mg/kg intravenously) with a 28-day observation, followed by up to five multidose cycles (one dose per week for 4 weeks), depending on tumor response. Expansion cohorts were initiated at 3.0 mg/kg in patients with melanoma (n = 16) and renal cell carcinoma (RCC; n = 15). Primary objectives were to assess the safety and the maximum tolerated and optimal biologic doses of varlilumab. Secondary objectives were to evaluate the pharmacokinetics, pharmacodynamics, and clinical antitumor activity of varlilumab. Results Exposure to varlilumab was linear and dose proportional across dose groups. Only one patient experienced a dose-limiting toxicity-grade 3 transient asymptomatic hyponatremia at the 1.0-mg/kg dose level. Treatment-related adverse events were generally grade 1 or 2 in severity. Evidence of biologic activity consistent with CD27 stimulation-chemokine induction, T-cell stimulation, regulatory T cell depletion-was observed at all dose levels. A patient with metastatic RCC experienced a partial response (78% shrinkage, progression-free survival > 2.3 years). Eight patients experienced stable disease > 3 months, including a patient with metastatic RCC with progression-free survival of > 3.9 years. Conclusion Dose escalation of varlilumab to 10 mg/kg was well tolerated without identification of a maximum tolerated dose. Varlilumab was biologically and clinically active.
Combined results of 4 phase I and pharmacokinetic (PK) studies of E7070, a novel chloroindolyl-sulphonamide inhibiting the activation of cdk2 and cyclin E
Authors: EE Raymond, P Fumoleau, H Roche, Jhm Schellens, C Dittrich, Cja Punt, JP Droz, AH Calvert, A van Oosterom, J Wanders, M Ravic
Journal: Clinical Cancer Research (2000)
A novel in vivo model for studying conditional dual loss of BLIMP‐1 and p53 in B‐cells, leading to tumor transformation
Authors: Antonio Sacco, Yawara Kawano, Michele Moschetta, Oksana Zavidij, Daisy Huynh, Michaela Reagan, Yuji Mishima, Salomon Manier, Jihye Park, Elizabeth Morgan, Satoshi Takagi, Kwok K. Wong, Ruben Carrasco, Irene M. Ghobrial, Aldo M. Roccaro
Journal: American Journal of Hematology (2017)

The tumor suppressors B-lymphocyte-induced maturation protein-1 (BLIMP-1) and p53 play a crucial role in B-cell lymphomas, and their inactivation contributes to the pathogenesis of a wide spectrum of lymphoid malignancies, including diffuse large B-cell lymphomas (DLBCLs). Patients with activated B-cell-like (ABC) DLBCL may present with loss of BLIMP-1, c-Myc over-expression, decreased p53, and poor prognosis. Nevertheless, there is a lack of in vivo models recapitulating the biology of high-grade ABC DLBCL. We therefore aimed to develop an in vivo model aiming to recapitulate the phenotype observed in this cohort of patients. A Cre-Lox approach was used to achieve inactivation of both p53 and BLIMP-1 in murine B-cells. Contextual ablation of BLIMP-1 and p53 led to development of IgM-positive B-cell lymphoma with an aggressive phenotype, supported by c-Myc up-regulation, and accumulation of somatic mutations, as demonstrated by whole exome sequencing. Sensitivity of B-tumor cells to BTK inhibition was demonstrated. This model mirrors what reported in patients with ABC DLBLC, and therefore represents a novel model for studying the biology of ABC-DLBCL harboring the dual loss of BLIMP-1/p53 and c-Myc over-expression.
Ex Vivo Expansion of Autologous Bone Marrow CD34+ Cells With Porcine Microvascular Endothelial Cells Results in a Graft Capable of Rescuing Lethally Irradiated Baboons
Authors: John E. Brandt, Amelia M. Bartholomew, Jeffrey D. Fortman, Mary C. Nelson, Edward Bruno, Luci M. Chen, Julius V. Turian, Thomas A. Davis, John P. Chute, Ronald Hoffman
Journal: Blood (1999)
Potent Anti-Leukemic Effects of Small Molecule ONC212, a Member of the Imipridone Class of Anti-Cancer Compounds
Authors: Varun V Prabhu, Rohinton S Tarapore, Mathew J Garnett, Ultan McDermott, Cyril H Benes, Jessica M Wagner, Wafik S. El-Deiry, Martin Stogniew, Wolfgang Oster, Joshua E Allen
Journal: Blood (2016)
S100-alarmin-induced innate immune programming protects newborn infants from sepsis
Authors: Thomas Ulas, Sabine Pirr, Beate Fehlhaber, Marie S Bickes, Torsten G Loof, Thomas Vogl, Lara Mellinger, Anna S Heinemann, Johanna Burgmann, Jennifer Schöning, Sabine Schreek, Sandra Pfeifer, Friederike Reuner, Lena Völlger, Martin Stanulla, Maren von Köckritz-Blickwede, Shirin Glander, Katarzyna Barczyk-Kahlert, Constantin S von Kaisenberg, Judith Friesenhagen, Lena Fischer-Riepe, Stefanie Zenker, Joachim L Schultze, Johannes Roth, Dorothee Viemann
Journal: Nature Immunology (2017)
Personalized Prognosis of Uveal Melanoma Based on Cytogenetic Profile in 1059 Patients over an 8-Year Period
Authors: Carol L. Shields, Emil Anthony T. Say, Murat Hasanreisoglu, Jarin Saktanasate, Brendan M. Lawson, Jeffrey E. Landy, Anjali U. Badami, Meera D. Sivalingam, Alexander J. Hauschild, Robert J. House, Zachary E. Daitch, Arman Mashayekhi, Jerry A. Shields, Arupa Ganguly
Journal: Ophthalmology (2017)
Use of Piezo-Immunosensors in Detecting Antigens and Antibodies Using Quartz Crystal Microbalance (QCM): a Novel Technique for Characterization, Understanding Interactions and Mechanisms of Action and Resistance of Monoclonal Antibodies
Authors: Mohammad Muhsin Chisti, Justin F. Klamerus, Norman Leo, Yupin Shang, Ishmael Jaiyesimi, Liang Tan, Peiling Lin, Abdul Rehman, Xiangqun Zeng
Journal: Blood (2016)
急性心不全症候群の患者の腎機能に及ぼすトルバプタンの影響,SAKURA AHFS登録からの解析
Authors: Iida Kiyoshi, Kato Mahoto, Fukushima Seiji, Nomoto Kazumiki, Tachibana Eizo, Ohiwa Koji, Kiso Daisuke, Yahagi Takayuki, Matsuzaki Masakazu, Ishii Mitsuru, Kumabe Narimichi, Nagao Ken, Hirayama Atsushi
Journal: Circulation (2014)
Epoetin delta in the management of anaemia in cancer patients
Authors: K. Zajda, M. Krzakowski
Journal: Journal of Clinical Oncology (2007)

19555 Background: Cancer is often associated with anaemia. Epoetin delta (Shire plc) differs from recombinant erythropoietins as it is produced in a human cell line using gene-activation technology. We report data from a controlled trial of epoetin delta (ED) and an extension study. Methods: Cancer patients with anaemia (haemoglobin [Hb] = 10.5 g/dL) were randomized to 12-weeks’ treatment with ED (150 or 300 IU/kg) or placebo (double blind). Treatment was given subcutaneously, three-times weekly. Patients were included if they were receiving chemotherapy and had at least two cycles remaining when randomized. Primary objective was to demonstrate a difference between ED and placebo in Δ Hb from baseline and the number of patients requiring blood transfusions. Target sample size was 100 patients per arm (99% power for a 1.6 g/dL difference in Δ Hb and a 29% difference in the percentage of patients requiring transfusions). Patients completing the study entered an open-label, 12-week extension in which all initially received ED 150 IU/kg. Dose could be increased to 300 IU/kg if Hb levels were &lt; 12 g/dL after 4 weeks. Results: In total, 313 patients were randomized (100, 103 and 99 to ED 150 and 300 IU/kg, and placebo, respectively). Mean change ± SD in Hb from baseline was 2.47 ± 2.39, 2.46 ± 2.56 and 0.57 ± 1.7 in the ED 150 and 300 IU/kg, and placebo groups respectively (P &lt; 0.0001 for both comparisons). There was no difference in the proportion of patients requiring transfusions (26.0, 21.9 and 26.9%, respectively). In the second study, Hb levels were maintained in those previously on ED and increased in those previously on placebo (2.55 g/dL). In those previously on ED, transfusion requirements were lower. ED was well tolerated. Conclusions: Epoetin delta was effective in increasing Hb levels in patients with anaemia related to cancer and longer treatment was associated with fewer transfusions. No significant financial relationships to disclose.
Abstract 325: Brain Natriuretic Peptide During Coronary Intervention Prevents Endothelial Dysfunction Post PCI via NP-cGMP Activation
Authors: Aviva Peleg, Yonathan Hasin
Journal: Circulation Research (2012)

Background: Contrast media (CM) administrated during percutaneous coronary intervention (PCI) is associated with endothelial dysfunction (ED) and systemic vascular injury. Brain natriuretic peptide (BNP) administration 24 hours post PCI decreases ED. Aims: To evaluate 1.The ability of human BNP (hBNP) infusion during PCI, to prevent ED in acute coronary syndrome's (ACS) patients post the PCI. 2. The effect of CM on human coronary microvascular endothelial cells (HCMEC).3. Explain ED by invitro study. Methods and results (in vivo): Non-ST elevation ACS patients who underwent PCI (111) were randomized into 2 groups: an hBNP group who received hBNP infusion during the procedure (n=44), and control group who received nitroglycerin (n=67). Flow mediated dilatation (FMD) (by ≥2.5%), BNP, corin, serum creatinine (sCr) and estimate Glomerular Filtration Rate (eGFR), before and 24 hr after operative were recorded, starting with the same baseline. The post PCI FMD and eGFR were significantly reduced in the control group (p=0.05, 0.002) but not in the hBNP group (p=0.16, 0.4). BNP, corin and sCr increased significantly in the control group (p=0.001, 0.003, 0.0002 respectively) but not in hBNP group (p=0.09, 0.07, 0.18). Methods and results (in vitro): HCMEC were treated with CM (10%) in the presence and absence of BNP. eNOS, corin and cGMP levels were measured by ELISA and the results were compared to untreated cells. In both treatments eNOS was significantly reduced (p=0.001) and corin was significantly increased (p=0.002). cGMP was not affected by CM treatment (p=0.278), but was increased significantly (p=0.001) by hBNP combination. cGMP immuno-flourescence staining of HCMEC showed distorted cellular cGMP appearance by CM treatment, that was corrected in the combination with hBNP with accentuated subsarcolemmal staining. Conclusions: CM reduces eNOS level in HCMEC. Therefore, reduced in NO-cGMP pathway's products, probably is the mechanism that induces ED in-vivo. BNP treatment reduces FMD diminution and kidney injury post PCI. A compensatory rise in corin that increases BNP as well as the hBNP administration, invivo and invitro, maintains cytosolic cGMP via NP-cGMP pathway, and compensates for NO-cGMP loss, (reduced sGC) and thus prevents ED.
Long-Term Follow up of a Comparison of Non-Myeloablative Allografting with Autografting for Newly Diagnosed Myeloma
Authors: Benedetto Bruno, Barry Storer, Francesca Patriarca, Marcello Rotta, Roberto Sorasio, Bernardino Allione, Fabrizio Carnevale-Schianca, Luisa Giaccone, Moreno Festuccia, Lucia Brunello, Paola Omedè, Federica Ferrando, Sara Bringhen, Massimo Aglietta, Alessandro Levis, Nicola Mordini, Andrea Gallamini, Antonio Palumbo, Renato Fanin, Rainer Storb, Ted Gooley, Mario Boccadoro
Journal: Blood (2010)
Targeted Inhibition of Activated Protein C Anticoagulant Activity By Monoclonal Antibody HAPC1573 for Treatment of Hemophilia
Authors: Xiao-Yan Zhao, Subramanian Yegneswaran, Maxine Bauzon, Derek Sim, Chandra Patel, Doug Schneider, Kirk McLean, Ying Zhu, Xiaoqiao Jiang, Vince Evans, Jian-Ming Gu, Inge Ivens, Jun Xu, Peter Wolfgang Bringmann, Katalin Kauser, Charles Esmon
Journal: Blood (2016)
ACUTE HEPATITIS ASSOCIATED WITH MOUSE LEUKEMIA
Authors: John B. Nelson
Journal: The Journal of Experimental Medicine (1953)

The mortality rate for 80 Swiss weanlings infected with mouse hepatitis was 2.5 per cent in comparison with 98 per cent for 140 Princeton weanlings. In Swiss weanlings discrete lesions, which generally failed to progress, were observed in the liver from the 3rd through the 10th day after intraperitoneal injection. The causal virus was demonstrable in peritoneal washings through the 21st day and less regularly in the liver through the 14th day. It was also detectable in both loci after subcutaneous injection. Infant Swiss mice were susceptible through the 10th day of life, intraperitoneal injection being commonly followed by death. The pathogenicity and titer of the virus were significantly increased by successive passage in Swiss weanlings. The virus was detected in the blood of Swiss weanlings on subcutaneous injection only after it had been modified by passage.
Enhanced Education for Noninvasive Cardiac Testing—Reply
Authors: Torrey Schmidt, Ronald Maag, Andrew J. Foy
Journal: JAMA Internal Medicine (2017)

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