tbuckley/cabot-search huggingface dataset:
Abstract 2955: LSm1 over expression contributes to an increase in alternative splicing in lung cancer cells
Authors: Patricia M. Watson, Alice Boylan, Dennis K. Watson
Journal: Cancer Research (2010)

Abstract RNA splicing is a key molecular event that allows for substantial protein diversity. Through this process, a single gene magnifies its coding capacity by expressing several related proteins with diverse and often antagonistic functions leading to cell or tissue specific changes in mRNA through changes in splice site choice. Alternative splicing, which represents the suppression of constitutive splice sites and/or the use of suboptimal sites, is elevated in cancer and many other disease states. Pre-mRNA splicing is coordinated by the spliceosome, a macromolecular ribonuclear complex that assembles on the pre-mRNA as it is transcribed. Due to the number of proteins involved in splicing, the diversity of pre-mRNA substrates and the multi-step process of spliceosome assembly and catalysis, regulation of splicing can occur at any point in the pathway. The LSm proteins are a family of eight RNA binding proteins that form two seven membered ring structures and contribute to mRNA stability and splicing. LSm1 forms a complex with LSm2-7 that targets mRNA for degradation in P bodies. LSm8 also forms a complex with LSm2-7 that binds the U4 U5 U6 tri-SNRP, an integral part of the spliceosome. Previously, it was shown that LSm1 was elevated in many different types of cancer and contributed to the malignant phenotype. Recently, alternative splicing has been shown to contribute to the activation of oncogenes and the inactivation of tumor suppressor genes. To determine if the over expression of LSm1 could contribute to alternative splicing, a well differentiated lung cancer cell line was infected with adenovirus expressing the open reading frame of LSm1 or GFP. The RNA from these cells was analyzed for alternative splicing using Agilent SpliceArray™ microarray slides. Significant differences were seen between the cells treated with control virus and the LSm1 expressing virus in the splicing patterns of several genes that could contribute to the cancer phenotype, including hepatoma derived growth factor (HDGF), CD44 and c-myc. Thus, over expression of LSm1 leads to changes in alternative splicing that impacts the malignant phenotype of cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2955.
Abstract 4453: Development of a crosslinked, daunorubicin-loaded micelle with superior pharmacokinetics compared to free daunorubicin and with tunable stability
Authors: Jonathan Rios-Doria, Tara L. Costich, Adam Carie, Kevin Sill
Journal: Cancer Research (2011)

Abstract Chemotherapeutic drugs are widely used for the treatment of cancer; however, use of these drugs is often associated with patient toxicity and poor delivery to the tumor. Poor delivery to the tumor can be attributed, in part, to rapid elimination of the drug by the reticuloendothelial system (RES), resulting in short circulation times. Nanoscopic drug carriers offer a promising approach to achieving improved delivery of chemotherapeutic drugs to tumors due to their size and ability to avoid RES uptake, but conventional nanoparticles are not stable in complex biological environments. This instability has resulted in little clinical success of conventional nanoparticles to date. Intezyne's IVECTTM Method, which utilizes triblock copolymers to form micelles that are stabilized to dilution in complex media, was used to encapsulate daunorubicin. The resulting daunorubicin loaded micelle's size was determined to be 60 nm by dynamic light scattering analysis. To generate stable micelles, iron (II) chloride was used to form pH-reversible iron-acetate crosslinking bonds in the outer core of the micelle. Release of daunorubicin from stabilized micelles was shown to be pH-dependent through the use of drug-release dialysis assays. Cytotoxicity studies in cancer cell lines revealed that the IC50 values of daunorubicin micelles were similar to free daunorubicin. In vivo, the AUC of daunorubicin released from stabilized daunorubicin micelles was up to 60-fold higher compared to free daunorubicin. Furthermore, the pharmacokinetic parameters were proportional to the iron (II) concentrations used for crosslinking. Repeated injections of daunorubicin micelles in rats showed little to no change in the pharmacokinetic parameters and did not exhibit accelerated blood clearance based on rat IgM ELISA measurements. These data report the development of a stabilized daunorubicin micelle that exhibits pH-dependent release and superior pharmacokinetics based on tunable crosslinking chemistry. 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 4453. doi:10.1158/1538-7445.AM2011-4453
Soundings: Science night
Authors: Trisha Greenhalgh
Journal: BMJ (1999)

“Science,” announced my 9 year old son recently, “is BORING.”

In a household where everything from cookery to bicycle maintenance is hypothesis driven, and where the younger sibling invariably has experiments on the go in the compost heap or outside drain, this statement is the ultimate heresy. We book our elder son and six friends in urgently for a night at the Science Museum.

For £20 a head, we get to pitch our sleeping bags under the exhibit of our choice—from a 30ft double helix to an original prototype of the internal combustion engine. Our own personal trainer in a red sweatshirt runs us from one hands on activity to another until just short of midnight, and resumes again at 6 30 am. Four hundred of us make our own slime by adding the three “carefully measured” and very smelly ingredients up to the black line in a tall plastic beaker, placing lids on tight, and shaking on down to Chubby Checker. The kids feel chemistry happen in their hands, and the slime goes into the party bag.

“Does hydrogen burn?” asks an impish demonstrator, as if she genuinely cannot remember. A show of hands suggests we are not sure either. She holds a taper to the balloon, which explodes in a blue flash and a loud bang. Everyone is now paying attention. Another demonstrator holds an air filled balloon in liquid nitrogen and we watch it slowly collapse—“Must be about minus 79 in there now, which means it’s snowing pure carbon dioxide”—and re-expand exactly on rewarming. This time, no bang. We discuss the anticlimax.

An astronaut in a space suit and with an authentic American accent tells us what we really wanted to know about flying to the moon—how to get the bubbles out of cherryade, and how to go to the lavatory when there is no “down.” Later, we have a midnight feast in the shadow of a real lunar module, and press a button to hear Neil Armstrong’s crackling voice, “One small step for a man....”

We’ve seen and heard most of it before, but when you’re sliding in your socks along the polished floors hours after official bedtime, and still no one is telling you to stop fiddling with the switches, science is no longer boring. My son is a willing convert to a career in science, which gives me an idea for the various recruitment crises in medicine. Anyone fancy running a sleep over at the Royal College of Psychiatrists?
AB0038 Adipokine expression in synovial tissue from patients with psoriatic arthritis
Authors: E. Schmitt, J. Kriegsmann, R. Straub, U. Müller-Ladner, E. Neumann
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The pathophysiology of psoriatic arthritis (PsA) is not as well understood as for rheumatoid arthritis (RA), and the distinction between both diseases is often difficult. However, both diseases are characterized by synovial alterations within the affected joints and the central involvement of pro-inflammatory factors. Adipokines such as adiponectin, visfatin/PBEF and resistin have recently been identified as signaling molecules with substantial immunomodulatory potential. These adipokines are increased in RA synovium and exert a pro-inflammatory impact on central cells of RA pathophysiology. <h3>Objectives</h3> Therefore, the synovial adipokine expression of adiponectin, visfatin/PBEF and resistin was evaluated in PsA synovium. <h3>Methods</h3> Synovial tissues from affected joints of PsA patients were stained with hematoxylin/eosin. Immunohistochemical staining against fibroblasts (vimentin), macrophages (CD16), T cells (CD3), B cells (CD20), vessels (collagen type IV) as well as against adiponectin, visfatin/PBEF and resistin were performed in serial sections. Additionally, adipokine expression was compared to the expression pattern of RA patients. <h3>Results</h3> In the majority of patients, the synovial tissue from PsA showed no hyperplasia of the lining layer in comparison to RA. 71% of the synovial tissue showed a high expression of Visfatin/PBEF. However resistin was less detectable in PsA lining layer, 71% showed a low resistin secretion. In comparison to RA, resistin expression was lower in PsA whereas visfatin/PBEF was comparable. In contrast to RA, the expression of adiponectin in the lining layer was completely absent in most PsA patients. 86 % of the samples showed moderate adiponectin signals, which were mainly located in the sublining in vessels showing a strong expression in PsA. In RA, the sublining showed adiponectin expression in the vessels but also by connective tissue cells. Resistin and visfatin/PBEF were detectable in the sublining and comparable between RA and PsA tissues. Adiponectin was expressed in inflammatory infiltrates in RA. However, this pattern was not present in PsA tissue. <h3>Conclusions</h3> The synovial membranes from PsA and RA show clear differences to those of RA-affected joints and are in part reflected by the adipokine expression. Specifically, adiponectin is more prominent in the RA than in the PsA lining layer. Adipokines may therefore play different roles in inflammatory processes operative in these chronic rheumatic diseases. <h3>Disclosure of Interest</h3> None Declared
Epsilon Aminocaproic Acid Therapy of Hereditary Angioneurotic Edema
Authors: Michael M. Frank, John S. Sergent, Michael A. Kane, David W. Alling
Journal: New England Journal of Medicine (1972)

Five patients with hereditary angioneurotic edema were treated with a sequence of courses of epsilon aminocaproic acid (EACA) or placebo in a double-blind study. Attacks of edema were significantly less frequent during administration of EACA in four patients. The principal adverse side effects of EACA – muscle pain and weakness, accompanied by elevations in the serum enzymes creatine phosphokinase and aldolase – were usually observed when the dose of drug exceeded 20 g per day, but disappeared when the drug was discontinued or the dosage was lowered.
SP0199 Implementation of effective cardiovascular training principles in daily practice
Authors: K. Niedermann
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> There is strong evidence that cardiovascular training programmes for people with rheumatic diseases, which are in accordance with current recommendations for enhancing physical fitness, are effective. For many reasons, such research findings often have little impact on clinical practice and it may be rather luck than planning, when research findings lead to a change in diagnostic or therapeutic procedures. <h3>Objective</h3> To present an overview of dissemination and implementation strategies and illustrate this with the example of implementing effective cardiovascular training for people with rheumatic diseases, e.g. Ankylosing Spondylitis (AS), in daily clinical practice. <h3>Methods</h3> The features of effective cardiovascular training and an overview of what an implementation process involves will be discussed. Generally, one of the two following approaches are applied: the more structured “rational model”, where new findings are considered worth to be introduced into routine and subsequently are disseminated and implemented with steering from external and above, or the “participation model”, which works bottom up, innovation is introduced incrementally and steered from practice. Different theories from other disciplines and scientific areas can be used to support the process of change, i.e. theories that address the individual health professionals’ behaviour change, theories that focus on the social interaction and context and finally, theories on factors related to the organisational or economic context. The implementation process itself is a systematic approach with clear strategies for dissemination, implementation and/or maintenance (1). In a project plan various steps must be addressed, such as attainable aims, the analysis of the target group and the setting, including the identification of barriers and facilitators for change as well as concrete activities and tasks within a schedule. After testing and executing the implementation plan, the final step is to evaluate the results in order to improve and adapt the procedures if necessary. <h3>Conclusions</h3> The key to successful implementation is a well planned and prepared process and systematic approach, no matter if the project is large or small and independent from aims, content or setting. Effective implementation helps to close the gap new evidence and daily practice and to provide the best available care to patients. <h3>References</h3> Grol R, Wensing M. What drives change? Barriers and incentives for achieving evidence-based practice. MJA. 2004, 180:557-60. <h3>Disclosure of Interest</h3> None Declared
P1321 : A phase 3B, double blind, placebo controlled study evaluating the effect of obeticholic acid on clinical outcomes in subjects with primary biliary cirrhosis at elevated risk of progression to liver transplant or death
Authors: K. Lindor, B. Hansen, R. Pencek, R. Hooshmand-Rad, T. Marmon, L. MacConell, D. Shapiro, D. Jones
Journal: Journal of Hepatology (2015)
Twiddler's Syndrome
Authors: William J. Nicholson, Kathryn A. Tuohy, Peter Tilkemeier
Journal: New England Journal of Medicine (2003)

To the Editor: First described in 1968, pacemaker twiddler's syndrome refers to permanent malfunction of a pacemaker due to the patient's manipulation of the pulse generator.1 The sequence of symptoms begins with the patient's deliberate or subconscious spinning of the pacemaker's pulse generator in a capacious pocket. The leads are dislodged, and ventricular pacing ceases. Subsequently, with continual reeling of the leads around the generator, the ipsilateral phrenic nerve is stimulated, resulting in diaphragmatic pacing and the sensation of abdominal pulsations. As the leads are further wrapped around the generator, rhythmic arm twitching occurs when the brachial plexus is paced. . . .
Profile: Animal Advocacy Organizations
Authors: S. Kumar
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Profile: Animal Advocacy Organizations Get access Seema Kumar Seema Kumar Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 20, 18 October 1989, Page 1527, https://doi.org/10.1093/jnci/81.20.1527 Published: 18 October 1989
MYO1E, Focal Segmental Glomerulosclerosis, and the Cytoskeleton
Authors: Julie R. Ingelfinger
Journal: New England Journal of Medicine (2011)

Focal segmental glomerulosclerosis, one of the most common glomerulopathies, is typically heralded by massive proteinuria, often associated with unremitting nephrotic syndrome and inexorable progression to end-stage kidney disease.13 Unfortunately, therapy is frequently unsuccessful — many patients with this disorder do not respond to treatment with glucocorticoids, and immunosuppressive therapy often fails as well. The disease also frequently recurs after kidney transplantation.The podocyte is critical to the development of focal segmental glomerulosclerosis. This dynamic cell controls glomerular filtration by means of its slit-pore diaphragm and other properties, which include motility along the glomerular basement membrane.4 Podocytes surround and adhere . . .
P602Sex-dependent perinatal alterations in plasma oxidative status in a rat model of fetal programming of hypertension
Authors: P Rodriguez, LA Condezo-Hoyos, AL Lopez De Pablo, G Ruiz-Hurtado, P Gutierrez, MC Gonzalez, D Munoz, SM Arribas
Journal: Cardiovascular Research (2014)

Purpose. Adverse intrauterine growth induced by maternal undernutrition during pregnancy (MUN) is associated with low birth weight of the offspring and later development of hypertension. This process, known as fetal programming, has less impact on female offspring, which exhibit lower levels of blood pressure in adult life compared to males. Given the role of oxidative stress in the development of cardiovascular diseases we aimed to asses if fetal programming induces perinatal alterations in oxidative-antioxidant balance and the possible differences between males and females.
Tc-99m Depreotide Scintigraphy of Low-Grade Non-Hodgkin’s Lymphoma
Authors: JAIME L. MONTILLA-SOLER, JASON T. REXROAD, ROBERT S. BRIDWELL
Journal: Clinical Nuclear Medicine (2003)

MONTILLA-SOLER, JAIME L. M.D.; REXROAD, JASON T. M.D.; BRIDWELL, ROBERT S. M.D., M.B.A.Author Information
P5-20-07: Estimation of Febrile Neutropenia in Women Receiving Docetaxel Plus Cyclophosphamide as Adjuvant Therapy for Early Stage Breast Cancer: A Retrospective Analysis.
Authors: RE Bordoni, ST Haislip, JW Gilmore, J Sharpe, E Abella, MR Choi
Journal: Cancer Research (2011)

Abstract Background: US Oncology Trial 9735 (Jones S, et al. JCO. 2006;24:5381–5387) established the docetaxel plus cyclophosphamide (TC) regimen as an effective adjuvant therapy for early stage breast cancer (ESBC). This trial did not specifically evaluate the incidence of febrile neutropenia (FN) as a study endpoint, but rates of 4%-8% were reported. Prophylactic granulocyte colony-stimulating factor (G-CSF) support was not allowed; reactive G-CSF support overall was not reported. Subsequent reports in the community setting have indicated FN rates of 25%-50% without G-CSF support and 0%-6.3% with G-CSF support (Table 1). To better determine the incidence of FN among ESBC patients treated with TC, we performed a retrospective clinical data review from the electronic medical record (EMR) database of Georgia Cancer Specialists, a large community oncology practice. Methods: EMR data were captured between January 2006 and March 2010. Eligibility included women ≥ 18 years old with ESBC (stage I-IIIA) who completed ≥ 1 cycle of TC. The study time period was from the first dose of chemotherapy (CTX) to 6 weeks after the last dose of CTX, death, or loss to follow-up. The primary endpoint was the incidence of FN. Other endpoints included the incidence of severe (grade 3/4) neutropenia, neutropenia-related hospitalizations, G-CSF use, relative dose intensity (RDI), and dose delays and reductions. Results: Data from 662 patients were included in the analysis. Median age was 55 (range: 25–81) years. 40% of patients were white. The median number of CTX cycles received was 4 (range: 1–6). Most patients (91%) received G-CSF support; 73% as primary prophylaxis. See Table 2 for additional results. Conclusions: This is the largest retrospective, community-based study to evaluate the incidence of FN in ESBC patients treated with TC. The observed FN rate of 5% (with 91% of patients receiving G-CSF) is consistent with other published reports using TC (Table 1). Our results suggest that TC is a taxane regimen with clinically significant myelosuppression (similar to other commonly used regimens in ESBC, such as TAC [NCCN Guidelines v2.2011]) and that the use of G-CSF support should always be considered. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-20-07.
Transplanted liver graft ischemia caused by pediatric ERCP in the prone position
Authors: Koichiro Tsutsumi, Hironari Kato, Hiroyuki Okada, Takahito Yagi, Kazuhide Yamamoto
Journal: Endoscopy (2014)

Endoscopic retrograde cholangiopancreatography (ERCP) for biliary complications after liver transplant is safe and useful in children and adults [1] [2] [3]. Here, we report a very rare case of a child in whom liver graft ischemia developed after therapeutic post-transplant ERCP.
PREDICTIVE VALUE OF CORONARY ARTERY DILATION RESPONSE TO NITRATES FOR DIAGNOSIS OF VASOSPASTIC ANGINA
Authors: Yuichi Saito, Hideki Kitahara, Toshihiro Shoji, Satoshi Tokimasa, Takashi Nakayama, Yoshihide Fujimoto, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2016)
Abstract LB-80: Building Bridges for Pancreatic Cancer Research
Authors: Jason Peckenpaugh
Journal: Cancer Research (2011)

Abstract Almost 40 years after President Nixon signed into law the National Cancer Act, the survival rate for pancreatic cancer has not substantially improved. Today, 75 percent of patients diagnosed with pancreatic cancer die within one year of diagnosis, and 94 percent of pancreatic cancer patients will die within five years of diagnosis. Although pancreatic cancer is the fourth leading cause of cancer death in the U.S., causing 36,800 deaths in 2010, only two percent of the National Cancer Institute's budget is spent on researching the disease ($89.4 million in 2009). Early detection tools for pancreatic cancer do not exist, and thus, patients are typically diagnosed after the disease has metastasized and surgery is no longer a possibility. Jason Peckenpaugh became an independent advocate for pancreatic cancer patients and research after seeing his father, Jon, bravely battle pancreatic cancer for 18 months until his passing in October 2009. Mr. Peckenpaugh's fight illustrates the statistics above, including his seven month quest to simply discover his diagnosis. The focus of his advocacy work is communicating scientific information with caregivers, patients, and the public, while sharing the perspective of patients and caregivers with oncologists and researchers. He is participating in the AACR Scientist&amp;lt;–&amp;gt;Survivor Program to improve my knowledge of cancer science and research so that he may become a patient advocate on GI cancer grant committees and/or research control boards. Despite the poor prognosis for patients with pancreatic cancer, this is a promising time for pancreatic cancer research, in part due to grants from the Stand Up 2 Cancer organization, advances in molecular profiling of tumors, and recent research showing the progression of pancreatic cancer. Pancreatic cancer needs a patient advocate at the table wherever gastrointestinal cancers and other cancers are being discussed. Patient advocates serve on grant review boards of the Food and Drug Administration, the Gastrointestinal Specialized Program of Research Excellence (GI SPORE), and other government research consortia. Mr. Peckenpaugh is a volunteer with the Pancreatic Cancer Action Network (PanCAN) and a volunteer fundraiser for the Lustgarten Foundation and Johns Hopkins University's pancreatic cancer research program. He has raised more than $14,000 for pancreatic cancer research since 2008. 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 LB-80. doi:10.1158/1538-7445.AM2011-LB-80
State Politics and the Fate of the Safety Net
Authors: Katherine Neuhausen, Michael Spivey, Arthur L. Kellermann
Journal: New England Journal of Medicine (2013)

Interview with Prof. Sara Rosenbaum on the health care safety net, Medicaid expansion, and access to care. (16:47)Download A proposed rule for reducing disproportionate-share-hospital payments encourages states to focus DSH funds on the hospitals that need it most. But if states not expanding Medicaid don't reallocate their DSH funds, safety-net hospitals and their patients will suffer.