tbuckley/cabot-search huggingface dataset:
Abstract 2365: Actopaxin: A novel regulator of cell migration and invasion in human hepatocellular carcinoma
Authors: Lui Ng, Ronnie Poon, BCY Wong, Roberta Pang
Journal: Cancer Research (2011)

Abstract Background: The mortality rate of hepatocellular carcinoma (HCC) is high due to tumor recurrence and development of metastasis, involving cell spreading, lamellipodia formation and cell migration. Formation of focal adhesions is a key regulator of cell motility and cell invasion. Actopaxin, a focal adhesion and cytoskeleton-associated protein, is required for such processes. The aim of this study was to examine the role of Actopaxin in HCC cell migration, invasion and development of metastasis. Methods: The expression of Actopaxin in primary and metastatic liver cancer cell-lines was examined by western blot and RT-PCR. The functional and molecular effects of Actopaxin expression were studied by transient as well as stable enforced expression or down-regulation in HCC cell-lines. Immunofluorescence staining for actin cytoskeleton and focal adhesion was performed to examine the effect of Actopaxin expression on cell shape, stress fiber organization, and focal adhesion. The clinicopathological significance of Actopaxin expression in tumorous tissues of 119 HCC patients was also investigated. Results: High protein level of Actopaxin was found in the metastatic HCC cell-lines compared with other non-metastatic HCC cell-lines. Expression of a shorter form of Actopaxin was also detected in some of these cell-lines. Comparing to Actopaxin (LF-Actopaxin), the unreported short form (SF-Actopaxin) lacks a fragment in the C-terminal and hence results in an incomplete 2nd CH domain which consists binding sites for its downstream activation targets. Expression of LF-Actopaxin but not SF-Actopaxin in HCC cell-lines was positively correlated with their migration and invasion potential in vitro, accompanied by altered expressions of several focal adhesion proteins as well as EMT proteins. Study in clinical samples showed that LF-Actopaxin expression was positively correlated with tumor size (p&amp;lt;0.05) while SF-Actopaxin expression was lower in HCC tumor compared with corresponding nontumorous liver (p&amp;lt;0.001) and lower in HCC with metastasis compared with HCC without metastasis (p&amp;lt;0.05). Conclusion: This study demonstrated for the first time the pro-migratory effects of Actopaxin in human HCC, and the existence of SF-Actopaxin which displays different expression pattern as well as functional and molecular effects. . Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2365. doi:10.1158/1538-7445.AM2011-2365
TCT-409 6 year experience with the Absorb bioresorbable vascular scaffold: The Maasstad Absorb Registry
Authors: George Vlachojannis, Valeria Paradies, Kees-Jan Royaards, Floris Kauer, Jochem Wassing, Martin van der Ent, Pieter Smits
Journal: Journal of the American College of Cardiology (2016)
18F-FDG PET/CT Demonstrates Renal Cell Cancer in a Transplant With Synchronous Intestinal Infection
Authors: Anwin Joseph Kavanal, Joyita Bharati, Shelvin Kumar Vadi, Krishan Lal Gupta, Rajender Kumar, Bhagwant Rai Mittal
Journal: Clinical Nuclear Medicine (2019)

We present a case of a 22-year-old man with history of allogenic renal transplantation on immunosuppression, who underwent F-FDG-PET/CT to characterize a lesion in the transplanted kidney on ultrasonogram and contrast-enhanced computed tomography imaging. PET/CT revealed FDG avid lesion in the transplanted kidney and mural thickening involving the distal ileum, ileocecal junction, and ileocolic lymph nodes. Subsequent histopathological examination from the renal lesion revealed renal cell carcinoma in the transplanted kidney. Additionally, endoscopic biopsy from the ileal thickening revealed granulomatous inflammation, suggesting tuberculosis, which was missed on both ultrasonogram and contrast-enhanced CT imaging.
Abstract 4573: 6-C-(E-phenylethenyl)-naringenin suppresses colorectal cancer growth by inhibiting cyclooxygenase-1
Authors: Haitao Li, Feng Zhu, Hanyong Chen, Ka Wing Cheng, Tatyana Zykova, Naomi Oi, Ronald A. Lubet, Ann M. Bode, Mingfu Wang, Zigang Dong
Journal: Cancer Research (2015)

Abstract Recent clinical trials raised concerns regarding the cardiovascular toxicity of selective cyclooxygenase-2 (COX-2) inhibitors and cyclooxygenase-1 (COX-1) is now being reconsidered as a target for chemoprevention. Our aims were to determine whether selective COX-1 inhibition could delay or prevent cancer development and also clarify the underlying mechanisms. Data clearly showed that COX-1 was required for maintenance of malignant characteristics of colon cancer cells or tumor promoter-induced transformation of preneoplastic cells. We also successfully applied a ligand-docking computational method to identify a novel selective COX-1 inhibitor, 6-C-(E-phenylethenyl)-naringenin (designated herein as 6CEPN). 6CEPN could bind to COX-1 and specifically inhibited its activity both in vitro and ex vivo. In colorectal cancer cells, it potently suppressed anchorage-independent growth by inhibiting COX-1 activity. 6CEPN also effectively suppressed tumor growth in a 28-day colon cancer xenograft model without any obvious systemic toxicity. Taken together, COX-1 plays a critical role in human colorectal carcinogenesis, and this specific COX-1 inhibitor merits further investigation as a potential preventive agent against colorectal cancer. Citation Format: Haitao Li, Feng Zhu, Hanyong Chen, Ka Wing Cheng, Tatyana Zykova, Naomi Oi, Ronald A. Lubet, Ann M. Bode, Mingfu Wang, Zigang Dong. 6-C-(E-phenylethenyl)-naringenin suppresses colorectal cancer growth by inhibiting cyclooxygenase-1. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4573. doi:10.1158/1538-7445.AM2015-4573
Messenger RNA therapy for rare genetic metabolic diseases
Authors: Pedro Berraondo, Paolo G V Martini, Matias A Avila, Antonio Fontanellas
Journal: Gut (2019)

Decades of intense research in molecular biology and biochemistry are fructifying in the emergence of therapeutic messenger RNAs (mRNA) as a new class of drugs. Synthetic mRNAs can be sequence optimised to improve translatability into proteins, as well as chemically modified to reduce immunogenicity and increase chemical stability using naturally occurring uridine modifications. These structural improvements, together with the development of safe and efficient vehicles that preserve mRNA integrity in circulation and allow targeted intracellular delivery, have paved the way for mRNA-based therapeutics. Indeed, mRNAs formulated into biodegradable lipid nanoparticles are currently being tested in preclinical and clinical studies for multiple diseases including cancer immunotherapy and vaccination for infectious diseases. An emerging application of mRNAs is the supplementation of proteins that are not expressed or are not functional in a regulated and tissue-specific manner. This so-called 'protein replacement therapy' could represent a solution for genetic metabolic diseases currently lacking effective treatments. Here we summarise this new class of drugs and discuss the preclinical evidence supporting the potential of liver-mediated mRNA therapy for three rare genetic conditions: methylmalonic acidaemia, acute intermittent porphyria and ornithine transcarbamylase deficiency.
Reflections on Relevance: &lt;i&gt;Psychotherapy and Psychosomatics&lt;/i&gt; in 2004
Authors: Richard Balon
Journal: Psychotherapy and Psychosomatics (2004)

Relevance of an article is a highly desirable yet hardly predictable quality at the time of its publication. Article relevance is frequently measured by the impact factor of the journal where the article is published. Furthermore, impact factor, citation index and citation analysis are used as a measure of research progress and scientific wealth of a nation. The wisdom and significance of this approach to relevance is debatable and thus discussed here. In 2004, Psychotherapy and Psychosomatics published a variety of articles which, in the author's view, are clinically relevant. Several selected clinically relevant issues reviewed in this article include: the conceptualization of fibromyalgia as a stress disorder; the psychosocial impact and psychosocial interventions in cancer; the impact of alexithymia on patient care; the possible relationship between depression and nutrition (namely intake of folate and pyridoxal phosphate); the significance of hypercoagulability in panic-like anxiety; the questionable value of single isomer drugs, and the relevance and adequacy of clinimetrics versus psychometrics in clinical research. The reviewed issues seem to be relevant to clinical practice, research or both, but also to our critical thinking, and the critical review of the developments in psychiatry and psychology.
More doctors are taking a break from training after foundation programme
Authors: Tom Moberly, Will Stahl-Timmins
Journal: BMJ (2019)

Less than 40% of doctors in training now move directly into specialty training after the foundation programme, data from the UK Foundation Programme Office show.1

In 2018, 37.7% of the doctors who completed foundation training went straight into core training, a run through training programme, or another specialty training post in the UK.



The proportion of doctors who choose to go …
Abstract 11538: Multiple Biomarkers Improve the Prediction of Cardiovascular Mortality in Patients on Chronic Hemodialysis
Authors: Furuhashi Kyuichi, Ishii Hideki, Takahasi Hiroshi, Aoyama Toru, Kamoi Daisuke, Kawamura Yoshihiro, Kumada Yositaka, Ishii Junichi, Mukohara Toyoaki
Journal: Circulation (2011)

Background: Patients on chronic hemodialysis (HD) are widely recognized to be at high risk for cardiovascular (CV) mortality, thus the more accurate prediction of CV mortality is clinically importa...
Progress Toward Poliomyelitis Eradication — Nigeria, January 2012–September 2013
Authors: Andrew Etsano, Faisal Shuaib, Pascal Mkanda, Richard Banda, Charles Korir, Melissa Corkum, Serigne Ndiaye, Samrawit Ashenafi, Frank Mahoney, John F. Vertefeuille, Cara C. Burns
Journal: MMWR Morbidity and Mortality Weekly Report (2013)
Abstract 1404: Regulation of 53BP1 by the structural nuclear protein NuMA
Authors: Naike Salvador Moreno
Journal: Cancer Research (2017)

Abstract Cells repair DNA double-strand breaks (DSB) through two major pathways: homologous recombination (HR) and non-homologous end joining (NHEJ). The choice between these two pathways is critical to cell survival and is altered in cancers. 53BP1 is a protein with an important role in this choice: it promotes NHEJ by blocking CtIP-dependent DNA resection. Here, we present a new negative regulation mechanism of 53BP1 that relies on the structural protein NuMA. This protein participates in mitotic spindle assembly, influences chromatin organization during the interphase and modulates the chromatin response to DNA damage. We identified NuMA in a proteomics analysis of a 53BP1-interacting proteins. The interaction was confirmed by reciprocal immunoprecipitation and with a FRET assay. In response to DSB, we measured greater than 50% decreased 53BP1-NuMA binding, which suggests that NuMA may restrain 53BP1 diffusion in the absence of DNA damage. Fluorescence correlation spectroscopy (FCS) measurements in cells expressing GFP-tagged 53BP1 support this hypothesis. Moreover, NuMA overexpression inhibited 53BP1 recruitment at DNA damage sites in laser microirradiation assays, whereas NuMA silencing had the opposite effect. 53BP1 plays an essential role in B cell class switch recombination and mediates PARP inhibitor sensitivity in BRCA1-null cells. NuMA overexpression prevented immunoglobulin switching, and overwrote cancer cell sensitivity to PARP inhibitors to the same extent as 53BP1 loss of function. Our results help understand how 53BP1 is controlled, and shed light on the mechanisms regulating PARPi sensitivity. Citation Format: Naike Salvador Moreno. Regulation of 53BP1 by the structural nuclear protein NuMA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1404. doi:10.1158/1538-7445.AM2017-1404
Prophylactic allergen immunotherapy with Der p 2 prevents murine asthma by regulating lung GM-CSF
Authors: Eline Haspeslagh, Manon Vanheerswynghels, Kim Deswarte, Justine Van Moorleghem, Alain Jacquet, Bart N. Lambrecht, Hamida Hammad
Journal: Journal of Allergy and Clinical Immunology (2019)
Lung Microbiota Contribute to Pulmonary Inflammation and Disease Progression in Pulmonary Fibrosis
Authors: David N. O’Dwyer, Shanna L. Ashley, Stephen J. Gurczynski, Meng Xia, Carol Wilke, Nicole R. Falkowski, Katy C. Norman, Kelly B. Arnold, Gary B. Huffnagle, Margaret L. Salisbury, MeiLan K. Han, Kevin R. Flaherty, Eric S. White, Fernando J. Martinez, John R. Erb-Downward, Susan Murray, Bethany B. Moore, Robert P. Dickson
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Idiopathic pulmonary fibrosis (IPF) causes considerable global morbidity and mortality, and its mechanisms of disease progression are poorly understood. Recent observational studies have reported associations between lung dysbiosis, mortality, and altered host defense gene expression, supporting a role for lung microbiota in IPF. However, the causal significance of altered lung microbiota in disease progression is undetermined.
A Trial Integrating Different Methods to Assess Psychosocial Problems in Primary Care
Authors: Antonio Piolanti, Sara Gostoli, Jessica Gervasi, Nicoletta Sonino, Jenny Guidi
Journal: Psychotherapy and Psychosomatics (2019)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; A number of studies have documented psychosocial problems, psychiatric morbidity and impaired quality of life in primary care patients. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; The aim of this trial was to test the usefulness of the joint use of different diagnostic interviews and self-rated questionnaires. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Two hundred consecutive patients in a primary care practice in Italy underwent the Structured Clinical Interview for DSM-5 and the Semi-Structured Interview for the Diagnostic Criteria for Psychosomatic Research (DCPR) in its recently revised form. As self-rated evaluations, the PsychoSocial Index, the Short-Form Health Survey and the Illness Attitude Scales were administered. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; There were 46 patients (23%) with at least 1 DSM-5 diagnosis. Eighty-eight patients (44%) had at least 1 DCPR diagnosis, mainly maladaptive illness behavior (26.5%), allostatic overload (15.5%) and demoralization (15%). There were 47 (23.5%) patients who had a DCPR diagnosis only; 5 subjects (2.5%) had a DSM diagnosis only. Patients with DCPR syndromes displayed significantly higher self-rated levels of stress, psychological distress and maladaptive illness behavior and significantly lower levels of quality of life and well-being than patients with no diagnoses. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; In a busy clinical setting, a simple self-rated questionnaire such as the PsychoSocial Index may afford a useful tool to unveil patient current distress. The DCPR can provide clinical information for a substantial number of patients who do not satisfy DSM-5 classification criteria and yet present with psychosocial problems, as measured by self-rated scales. The DCPR may improve the assessment and treatment plan of primary care psychologists or consulting psychiatrists.
Bortezomib-Based First Line Treatment for AL Amyloidosis Patients Who Are Not Candidate for Stem Cell Transplantaion
Authors: Joon Young Hur, Kang Kook Lee, Sang Eun Yoon, Sehhoon Park, Jangho Cho, Youjin Kim, Eunseok Jeon, Jinoh Choi, Gayeon Lee, Byungjun Kim, Ju Hong Min, Jung Sun Kim, Jung Eun Lee, Joon Young Choi, Seok Jin Kim, Jun Ho Jang, Won-Seog Kim, Chul Won Jung, Kihyun Kim
Journal: Blood (2018)
Invasive Cancer Incidence and Survival — United States, 2012
Authors: S. Jane Henley, Simple D. Singh, Jessica King, Reda J. Wilson, Mary Elizabeth O’Neil, A. Blythe Ryerson
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

Many factors contribute to changes in cancer incidence, including changes in risk exposures or changes in the use of cancer screening tests (1). To monitor changes in cancer incidence and assess progress toward achieving Healthy People 2020 objectives, CDC analyzed data from U.S. Cancer Statistics (USCS) for 2012, the most recent data available. USCS includes high quality incidence data from CDC's National Program of Cancer Registries (NPCR) and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, survival data from NPCR, and mortality data from the National Vital Statistics System (2). In 2012, a total of 1,529,078 invasive cancers were reported to cancer registries in the United States (excluding Nevada), for an annual incidence rate of 440 cases per 100,000 persons. Cancer incidence rates were higher among males (483) than females (412), highest among blacks (446), and ranged by state, from 371 to 515 per 100,000 persons (355 in Puerto Rico). The proportion of persons with cancer who survived ≥5 years after diagnosis was 66%. The proportion was the same for males and females (66%) but lower among blacks (60%) compared with whites (66%). These cancer incidence, survival, and mortality surveillance data are continually tracked and used by states to effectively plan health care allocation and support services.
P051/O01 Characterization of the anti-centromere antibody response in systemic sclerosis patients suggests a broad and active B cell response
Authors: CM Wortel, NM van Leeuwen, M Boonstra, JA Bakker, RE Toes, TW Huizinga, JK de Vries-Bouwstra, HU Scherer
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> Systemic Sclerosis (SSc) is a rare, heterogeneous autoimmune disease characterized by microvascular damage, organ fibrosis and immune dysfunction. Autoantibodies are detected in &gt;95% of patients, the most prevalent being anti-centromere (ACA) and anti-topoisomerase (ATA) antibodies. Although used for diagnosis, little is known about the underlying auto-reactive B cell responses. In particular, the ACA B cell response has been poorly studied. <h3>Objectives</h3> Characterization of the ACA B cell response in SSc patients. <h3>Methods</h3> ACA IgG, IgA and IgM levels were measured in serum samples of 167 ACA IgG+ SSc patients. Patients were divided in a SSc (fulfilling ACR 2013 criteria, n=132) and a very early SSc group (fulfilling VEDOSS criteria, n=35). Additionally, PBMCs from ACA IgG+ SSc patients (and ATA IgG+ SSc and healthy donors (HD) as control) were cultured either in the presence of CD40L expressing fibroblasts, IL-21 and BAFF or without stimulation. Levels of ACA IgG, IgA and IgM (and total Ig) were measured after one week of culture using ELISA. <h3>Results</h3> ACA IgG+ SSc patients displayed a broad isotype usage with 75% being ACA IgA+ and 68% being ACA IgM+ in serum. Patients within the SSc group showed higher ACA IgG levels and a higher percentage of ACA IgM positivity compared to the very early SSC group. ACA IgG, IgA and IgM could be measured in ACA SSc PBMC culture medium following stimulation, but not in ATA SSc and HD, indicating the presence of circulating ACA B cells of all three isotypes. In cultures that yielded sufficient Ig production, ACA IgG was detectable in 7/9 ACA SSc patients, ACA IgA in 3/7 and ACA IgM in 2/7. Furthermore, ACA IgG production was also detected in the absence of stimulation in 5/9 patients, suggesting the presence of ACA-producing plasmablasts in the circulation. No spontaneous production of anti-Tetanus Toxoid antibodies, a control recall response, was observed. <h3>Conclusions</h3> ACA+ SSc patients display a broad range of isotype usage in their ACA response, reflected both by ACA serum levels and presence of ACA IgG-, IgA- and ACA IgM-producing B cells in the peripheral blood. Additionally, ACA IgG production by unstimulated PBMCs points towards continuous differentiation of memory cells into antibody secreting cells. These data, together with differential isotype profiles between very early SSc and SSc patients, provide insight into the ACA B cell response and its potential involvement in disease-relevant pathogenetic processes. <h3>Disclosure of Interest</h3> None declared.
Thorax at 60
Authors: A E Tattersfield
Journal: Thorax (2006)

Editors look for articles that say something new, and studies don’t have to be large and grand. I have selected two papers and an editorial from among the many I could have chosen. They may not be landmark articles, but they are probably the three articles I have quoted most widely in discussions and teaching. I enjoy the fact that the two studies are simple, showing that valuable information can still be obtained by studying patients carefully and without breaking the bank.

First is a paper by Tweedale et al 1 which looked at short term repeatability of FEV1 and bronchodilator responsiveness in patients with airflow obstruction. The authors showed that within subject differences in FEV1 …
Recipients of Myelotoxic Chemotherapy Have Increased Prevalence of Clonal Hematopoiesis of Indeterminate Potential (CHIP) with a Typical Distribution of Chip-Associated Mutations
Authors: Adam J Olszewski, Anna Dorota Chorzalska, Annette S. Kim, Peter J. Quesenberry, Mary L Lopresti, Mary Anne Fenton, John L. Reagan, James Butera, Ilyas Sahin, Celine Hamel, Jordan Robison, Max Petersen, Patrycja Dubielecka
Journal: Blood (2018)
Hydrodynamic Injection of Helper Dependent Adenoviral Vectors Increases Liver Transduction Efficiency and Decreases Acute Inflammatory Response
Journal: Molecular Therapy (2004)

Top of pageAbstract
Hydrodynamic injection of helper–dependent adenoviral vectors (HDAd) in mice results in significantly higher efficiency hepatic transduction and significantly higher levels of transgene expression compared to conventional injection without compromising duration of expression. Furthermore, significantly less splenic transduction was observed following hydrodynamic injection compared to conventional injection. These results suggest that hydrodynamic injection alters vector biodistribution to favor transduction of the liver and consequently reduce transduction of other organs. Moreover, elevations in IL–6 and IL–12 were less following hydrodynamic than conventional injection suggesting that activation of the innate inflammatory response may be reduced by minimizing systemic exposure/transduction through preferential hepatic transduction. Although systemic hydrodynamic injection is not possible in large animals, localized hydrodynamic injection may provide a method of achieving efficient HDAd–mediated hepatic transduction and minimizing the acute inflammatory immune response.
Eltrombopag maintains human hematopoietic stem and progenitor cells under inflammatory conditions mediated by IFN-γ
Authors: Luigi J. Alvarado, Heather D. Huntsman, Hai Cheng, Danielle M. Townsley, Thomas Winkler, Xingmin Feng, Cynthia E. Dunbar, Neal S. Young, Andre Larochelle
Journal: Blood (2019)