tbuckley/cabot-search huggingface dataset:
Abstract 4730: Molecular analysis of the pediatric cancer fibrolamellar hepatocellular carcinoma
Authors: Elana P. Simon, Joshua N. Honeyman, David G. Darcy, Brad R. Rosenberg, Iris I. Lim, Jennifer M. Murphy, Ben Farber, Gadi Lalazar, Catherine Freije, Michael P. La Quaglia, Sanford M. Simon
Journal: Cancer Research (2015)

Abstract Genomic analysis of the pediatric cancer fibrolamellar hepatocellular carcinoma Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare liver tumor that usually occurs in adolescents and young adults. Originally considered a variant of hepatocellular carcinoma (HCC), FLHCC is characterized by hepatocytes with deeply eosinophilic, granular cytoplasm interspersed with fibrous bands, without signs of cirrhosis as in HCC. Since little is known of its molecular pathogenesis, we performed RNA-seq and whole genome sequencing of FLHCC paired with normal liver from the same patient. Our results demonstrated that the majority of the DNA is unremarkable with few recurrent mutations or structural variants such as amplifications or inversions The major finding is a heterogeneous deletion of ∼400 kB in chromosome 19 which produces a chimeric transcript and a fully functional protein, a fusion between the heat shock protein DNAJB1 and the catalytic subunit of protein kinase A (PRKACA). Our initial observation of this chimera in 15 out of 15 patients has now been expanded to 116 out of 116 patients. Differential expression analysis of RNA-seq revealed many changes in the gene expression in FLHCC as compared to its paired normal liver. These changes were highly consistent from patient to patient, suggesting a unifying pathogenesis. The RNA-seq from our FLHCC samples had little in common with HCC samples from the TCGA or published reports of other cancers. An analysis of protein expression correlated well with the RNA-seq results. Some observed changes can directly be linked to increased activity of PRKACA. Other changes involve pathways known to participate in the initiation and progression of other cancers, which, along with an increase of PRKACA activity, represent targets for therapeutic intervention. Several of these targets are now being explored in cellular models, genetic, and PDX mouse models, as well as clinical trials. Citation Format: Elana P. Simon, Joshua N. Honeyman, David G. Darcy, Brad R. Rosenberg, Iris I. Lim, Jennifer M. Murphy, Ben Farber, Gadi Lalazar, Catherine Freije, Michael P. La Quaglia, Sanford M. Simon. Molecular analysis of the pediatric cancer fibrolamellar hepatocellular carcinoma. [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 4730. doi:10.1158/1538-7445.AM2015-4730
Chemotherapy in the management of metastatic adenoid cystic carcinoma: A systematic review
Authors: S. A. Laurie, Y. B. Su, D. G. Pfister
Journal: Journal of Clinical Oncology (2005)

5581 Background: Adenoid cystic carcinomas [ACC] originate from a variety of sites, most commonly from the salivary glands. While generally not curable once metastatic, the disease course may be protracted and indolent. The precise role of systemic therapy [ST] in the management of advanced ACC is controversial. Methods: A systematic search of the medical literature was performed to find reports of ST for metastatic ACC. Outcomes of interest included antitumor activity (rates and durations of objective responses and stable disease), and symptom improvement. Clinical trial quality was assessed using the methodological scoring system for phase II/III trials of the European Lung Cancer Working Party [ELCWP], in which 100 is the highest score possible. Evidence-based recommendations were developed for the management of metastatic ACC. Results: 27 reports (3 retrospective reviews, 7 of single agents, 15 of combination chemotherapy regimens, 2 of imatinib) were included. Trial ELCWP scores were highly variable (median 49, range 22 to 81). Higher response rates [RR] were reported by retrospective reviews and trials of lower quality. While doxorubicin is often recommended as an active agent in ACC, little data exist for this as a single agent. Modest activity was seen with single-agent mitoxantrone and vinorelbine (both RR 10 - 15%), and cisplatin-anthracycline based combination chemotherapy regimens (RR up to 30%). Combination therapy may lead to higher RR, but is not clearly superior to single-agent treatment with regard to survival. There are insufficient prospective data to support the use of imatinib (0 major responses in 25 patients [pts]), other targeted agents, paclitaxel (0 major responses in 14 pts) or hormonal therapies. Symptom improvement was observed in some pts, including those without an objective response. Conclusions: The evidence in support of the efficacy of any ST for metastatic ACC is limited. ST should be reserved for those pts with disease-related symptoms or rapidly progressive disease. Single-agent mitoxantrone or vinorelbine, and cisplatin-anthracycline based combination therapy are reasonable choices. Enrollment of pts into high quality trials is needed to define the usefulness of ST in ACC. No significant financial relationships to disclose.
P1085 : Mechanistic insight into acetaminophen-induced hepatic tight junction disruption using a human HepaRG-based liverbiochip impedance biosensor
Authors: W. Gamal, P. Treskes, K. Morgan, C. Chesne, V. Shevchenko, J.N. Plevris, P.O. Bagnaninchi, L.J. Nelson
Journal: Journal of Hepatology (2015)
Analysis of matrix metalloproteinases, especially MMP‐8, in gingival crevicular fluid, mouthrinse and saliva for monitoring periodontal diseases
Authors: Timo Sorsa, Ulvi K. Gursoy, Solomon Nwhator, Marcela Hernandez, Taina Tervahartiala, Jussi Leppilahti, Mervi Gursoy, Eija Könönen, Gulnur Emingil, Pirkko J. Pussinen, Päivi Mäntylä
Journal: Periodontology 2000 (2015)

Matrix metalloproteinase-8 is a promising candidate biomarker for oral fluid (gingival crevicular fluid, peri-implant sulcular fluid and saliva) and mouthrinse chair-side/point-of-care diagnostics to predict, diagnose and determine the progressive phases of episodic periodontitis and peri-implantitis, as well as to monitor the treatments and medications. Matrix metalloproteinase-8 can be used alone or together with interleukin-1beta and Porphyromonas gingivalis to calculate cumulative risk score at the subject level as a successful diagnostic tool, especially in large-scale public health surveys, in which a thorough periodontal examination is not feasible.
A standardized approach for managing chemotherapy-induced rash.
Authors: Laura Poggi, Jennifer Godden, Sol Yoder
Journal: Journal of Clinical Oncology (2014)

86 Background: Chemotherapy-induced rash can lead to disruptions or discontinuation of therapy, potentially leading to a poorer prognosis for patients. Methods: A retrospective chart review was performed at selected clinics to determine rash incidence, current rash management, and dose reductions, disruptions, and discontinuation of therapy due to rash for epidermal growth factor receptor-inhibitors (EGFR-I) during August and September 2013. A rash management algorithm containing preventative and treatment recommendations was created for selected EGFR-I (cetuximab, panitumumab, erlotinib) and implemented in the clinics’ electronic medical record as part of a pilot study from February through May 2014. When the EGFR-I were ordered, electronic alerts reminded providers of the algorithm. Pharmacists received electronic messages to ensure algorithm compliance. Nurses provided patients with a rash information sheet and preventative prescriptions. Providers assessed patients for rash during follow-up and instituted the rash treatment algorithm, if indicated. Through a chart review, rash incidence, and dose reductions, disruptions, and discontinuation of therapy due to rash were determined. Results: The retrospective chart review revealed 7 of 9 (78%) patients, in whom preventive medications were not utilized, developed rash with the selected EGFR-I. Treatment medications were required in 6 of 7 (86%) patients with rash. Even with treatment, 3 of 7 (43%) patients had a severe rash, making therapy modification necessary. A dose reduction was ordered for 1 patient, a disruption for another, and discontinuation of therapy for a third. During the pilot period, 6 of 7 (86%) patients developed rash, but none required dose reductions or discontinuation of therapy. Of the 6 patients who developed rash, 4 were adequately managed with preventive measures alone. Of the 2 patients who started rash treatment, 1 patient had rash resolution and the other patient continued treatment without any therapy modifications. Conclusions: An algorithm containing preventive and treatment recommendations for EGFR-I-induced rash may be more beneficial than reactive therapy alone in attenuation of dose reductions, disruptions, and discontinuation of therapy.
Accuracy and feasibility of contrast echocardiography for detection of perfusion defects in routine practice
Authors: Thomas H Marwick, Richard Brunken, Nils Meland, Eric Brochet, Frank M Baer, Thomas Binder, Frank Flachskampf, Otto Kamp, Christoph Nienaber, Petros Nihoyannopoulos, Luc Pierard, Jean-Louis Vanoverschelde, Poll van der Wouw, Kaj Lindvall
Journal: Journal of the American College of Cardiology (1998)
Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse
Authors: Ye Zhang, Steven A. Sloan, Laura E. Clarke, Christine Caneda, Colton A. Plaza, Paul D. Blumenthal, Hannes Vogel, Gary K. Steinberg, Michael S.B. Edwards, Gordon Li, John A. Duncan, Samuel H. Cheshier, Lawrence M. Shuer, Edward F. Chang, Gerald A. Grant, Melanie G. Hayden Gephart, Ben A. Barres
Journal: Neuron (2015)
Gene expression of INPP5F as an independent prognostic marker in fludarabine-based therapy of chronic lymphocytic leukemia
Authors: G Palermo, D Maisel, M Barrett, H Smith, G Duchateau-Nguyen, T Nguyen, R-F Yeh, A Dufour, T Robak, D Dornan, M Weisser
Journal: Blood Cancer Journal (2015)

Abstract Chronic lymphocytic leukemia (CLL) is a heterogeneous disease. Various disease-related and patient-related factors have been shown to influence the course of the disease. The aim of this study was to identify novel biomarkers of significant clinical relevance. Pretreatment CD19-separated lymphocytes ( n =237; discovery set) and peripheral blood mononuclear cells ( n =92; validation set) from the REACH trial, a randomized phase III trial in relapsed CLL comparing rituximab plus fludarabine plus cyclophosphamide with fludarabine plus cyclophosphamide alone, underwent gene expression profiling. By using Cox regression survival analysis on the discovery set, we identified inositol polyphosphate-5-phosphatase F ( INPP5F ) as a prognostic factor for progression-free survival ( P &lt;0.001; hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.35–1.98) and overall survival ( P &lt;0.001; HR, 1.47; 95% CI, 1.18–1.84), regardless of adjusting for known prognostic factors. These findings were confirmed on the validation set, suggesting that INPP5F may serve as a novel, easy-to-assess future prognostic biomarker for fludarabine-based therapy in CLL.
PPAR-δ is repressed in Huntington's disease, is required for normal neuronal function and can be targeted therapeutically
Authors: Audrey S Dickey, Victor V Pineda, Taiji Tsunemi, Patrick P Liu, Helen C Miranda, Stephen K Gilmore-Hall, Nicole Lomas, Kunal R Sampat, Anne Buttgereit, Mark-Joseph Manalang Torres, April L Flores, Martin Arreola, Nicolas Arbez, Sergey S Akimov, Terry Gaasterland, Eduardo R Lazarowski, Christopher A Ross, Gene W Yeo, Bryce L Sopher, Gavin K Magnuson, Anthony B Pinkerton, Eliezer Masliah, Albert R La Spada
Journal: Nature Medicine (2015)
Exciting treatment of reentrant arrhythmias
Authors: H. V. M. van Rijen, J. M. T. de Bakker, T. A. B. van Veen
Journal: Cardiovascular Research (2010)

This editorial refers to ‘Expression of skeletal muscle sodium channel (Nav1.4) or connexin32 prevents reperfusion arrhythmias in murine heart’ by E.P. Anyukhovsky et al. , doi:10.1093/cvr/cvq284. 

Circulating cardiac excitation was first described by George R. Mines in his seminal publication ‘On dynamic equilibrium in the heart’.1 Mines recognized the importance of his finding and suggested that circulating excitation may be responsible for ‘some cases of paroxysmal tachycardia as observed clinically’, and directly defined the optimal circumstances for circular excitation: ‘The circumstances under which the phenomenon made its appearance were such as to produce the favourable conditions of slow conduction and short refractory period'.

During acute myocardial ischaemia, [K+]o is increased which leads to a reduced membrane potential and partial inactivation of the cardiac Na+ current (Nav1.5). Secondly, ischaemia leads to intracellular acidification,2 which in turn leads …
Prostate cancer screening in men aged 50–69 years (STHLM3): a prospective population-based diagnostic study
Authors: Henrik Grönberg, Jan Adolfsson, Markus Aly, Tobias Nordström, Peter Wiklund, Yvonne Brandberg, James Thompson, Fredrik Wiklund, Johan Lindberg, Mark Clements, Lars Egevad, Martin Eklund
Journal: The Lancet Oncology (2015)
The Future of General Surgery Residency Education
Authors: Mary E. Klingensmith
Journal: JAMA Surgery (2015)

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Parental awareness was high
Authors: A. Varghese, N. A Woodall
Journal: BMJ (1995)

Parental awareness was high EDITOR,-We wish to report the results of an observational study that a group of us under- took recently as part of our community medicine attachment.We chose the topic of measles immunisation because it was a current issue.'There had also been public concern that the campaign contained information contradicting that given in the previous measles, mumps, and rubella campaign, launched in October 1988.At that time the parliamentary secretary for health, Mrs Edwina Curry, stated that "It [measles, mumps, and rubella vaccine] provides life-long protection against all three infections with a single jab."2A third point of interest was the controversy surrounding the rubella component of the vaccine.
Factors predicting mortality in cystic fibrosis where lung transplantation can not be performed
Authors: Yasemin Gokdemir, Ela Erdem, Fazilet Karakoc, Bulent Karadag, Ihsan Nuri Akpinar, Refika Ersu
Journal: European Respiratory Journal (2012)

Introduction: Cystic fibrosis is the most common lethal genetic disorder affecting the Caucasian population. Severe pulmonary disease is responsible for over 80% of deaths associated with cystic fibrosis. Patients with less than 2 years life expectancy and with reduced quality of life are candidates for lung transplantation.  Aim: To evaluate the risk factors of mortality in moderate to severe cystic fibrosis lung disease that doesn9t go to lung transplantation.  Material and methods: We follow up 200 cystic fibrosis patients in our clinic and 35 of them with FEV1 ≤%60 were enrolled to the study. Demographic data, pulmonary function test, high resolution computed tomography modified Bhalla score, blood gas analysis and nutritional status of patients were evaluated.  Results: Respiratory support requirement was frequent in moderate to severe lung disease (31.4%). Low pulmonary function, non invasive ventilation requirement, having diabetes mellitus, 0 2  saturation  2  >50 mm Hg and frequent IV antibiotic treatment were significantly related with increased mortality (p  Conclusion: This is a single centre study of cystic fibrosis patients with moderate to severe lung disease that did not go to lung transplantation. We evaluated the clinical going and factors that were associated with mortality. We think that it is important to do similar multicentre studies to discover Turkish CF patients9 information that have different genetics and phenotype.
Lesson of the Week: Paradoxical embolism in a young woman
Authors: A T Edwards, S Vig, M A Denvir, A Wood, A Wood
Journal: BMJ (1996)

uncommon also.Those found by screening to have hepatitis C should be advised to avoid sharing needles, minimise alcohol intake, and use barrier methods of contraception in new relationships.Wider introduction of needle exchange schemes and health education pro- grammes might prove to be more practical and cost effective than mass screening for reducing the spread of hepatitis C. ConclusionsPeople who request hepatitis C screening should be offered careful counselling before testing.There should be specialist follow up for those found to be infected.More widespread screening of asymptomatic individ- uals cannot be justified until the course of the disease is better understood, treatment with clear clinical benefit becomes available, or a vaccine is produced.
Frequency of Perceived Poststress Symptoms in Inpatients, Outpatients and Healthy Controls: The Role of Perceived Exhaustion and Stress
Authors: Sandra Waeldin, Dominic Vogt, Michael Linden, Dirk H. Hellhammer
Journal: Psychotherapy and Psychosomatics (2015)

Poststress symptoms occur as a consequence of stress, most commonly during leisure periods such as weekends and vacations. However, the prevalence and the pathological mechanisms of poststress symptoms are poorly understood.Here, we compared the frequency of poststress symptoms in healthy controls (n = 984), outpatients (n = 420), and inpatients (n = 101). In outpatients, demographic factors, psychosocial stress, and perceived exhaustion were tested as predictors of poststress symptoms with multivariate regression analysis. Poststress symptoms and perceived exhaustion were assessed using 2 Neuropattern Questionnaires (the NPQ - Patient Questionnaire and the NPQ - Symptom List), and psychosocial stress was evaluated using the Patient Health Questionnaire (PHQ).Poststress symptoms appeared in 2.9% of healthy controls, 20.0% of outpatients, and 34.7% of inpatients. Predictors were educational level, psychosocial stress, and perceived exhaustion. Poststress symptoms differed primarily between exhausted (75.0%) and nonexhausted patients (25.0%).Poststress symptoms are rather common in clinical populations, and they are primarily associated with the degree of perceived exhaustion. Preliminary evidence suggests that poststress symptoms are possibly related to depletion of norepinephrine stores, which may facilitate a stratified preventive and therapeutic treatment of these subjects.
IgE epitope proximity determines immune complex shape and effector cell activation capacity
Authors: Anna Gieras, Birgit Linhart, Kenneth H. Roux, Moumita Dutta, Marat Khodoun, Domen Zafred, Clarissa R. Cabauatan, Christian Lupinek, Milena Weber, Margarete Focke-Tejkl, Walter Keller, Fred D. Finkelman, Rudolf Valenta
Journal: Journal of Allergy and Clinical Immunology (2015)

BackgroundIgE-allergen complexes induce mast cell and basophil activation and thus immediate allergic inflammation. They are also important for IgE-facilitated allergen presentation to T cells by antigen-presenting cells.ObjectiveTo investigate whether the proximity of IgE binding sites on an allergen affects immune complex shape and subsequent effector cell activation in vitro and in vivo.MethodsWe constructed artificial allergens by grafting IgE epitopes in different numbers and proximity onto a scaffold protein. The shape of immune complexes formed between artificial allergens and the corresponding IgE was studied by negative-stain electron microscopy. Allergenic activity was determined using basophil activation assays. Mice were primed with IgE, followed by injection of artificial allergens to evaluate their in vivo allergenic activity. Severity of systemic anaphylaxis was measured by changes in body temperature.ResultsWe could demonstrate simultaneous binding of 4 IgE antibodies in close vicinity to each other. The proximity of IgE binding sites on allergens influenced the shape of the resulting immune complexes and the magnitude of effector cell activation and in vivo inflammation.ConclusionsOur results demonstrate that the proximity of IgE epitopes on an allergen affects its allergenic activity. We thus identified a novel mechanism by which IgE-allergen complexes regulate allergic inflammation. This mechanism should be important for allergy and other immune complex–mediated diseases.
Retraction: Ahimastos AA, Dart AM, Kingwell BA. Angiotensin II blockade in Marfan’s syndrome. N Engl J Med 2008;359:1732
Authors: Jeffrey M. Drazen, Stephen Morrissey, Edward W. Campion
Journal: New England Journal of Medicine (2015)

requested retraction of their letter to the editor 1 owing to "inadequate validation of primary data sources and data misrepresentation" uncovered by an institutional investigation into the research of Anna A. Ahimastos
Extreme Length and Length Variation in the First Ribosomal Internal Transcribed Spacer of Ladybird Beetles (Coleoptera: Coccinellidae)
Authors: J H von der Schulenburg, J M Hancock, A Pagnamenta, J J Sloggett, M E Majerus, G D Hurst
Journal: Molecular Biology and Evolution (2001)

DNA sequences of the first ribosomal internal transcribed spacer (ITS1) were isolated from 10 ladybird beetle species (Coleoptera: Coccinellidae) representing four subfamilies (Coccinellinae, Chilocorinae, Scymninae, and Coccidulinae). The spacers ranged in length from 791 to 2,572 bp, thereby including one of the longest ITS1s and exhibiting one of the most extreme cases of ITS1 size variation in eukaryotes recorded to date. The causes of length variation were therefore analyzed. Almost no putatively homologous sequence similarities were identified for the taxa included. The only exception was for the subfamily Coccinellinae, which yielded sequence similarities in six regions of approximately 550 nucleotide positions, primarily at the 5′ and 3′ ends of ITS1. The majority of differences in ITS1 length between taxa could be attributed to the presence of repetitive elements with comparatively long repeat units. Repetition arose several times independently and was confined to the middle of the spacer which, in contrast to the 5′ and 3′ ends, had not been inferred in previous studies to be subject to functional constraints. These elements were characterized by high rates of evolutionary change, most likely as a result of high substitution rates in combination with inefficient homogenization across repeats. The repeated origin and subsequent divergence of "long" repetitive elements should thus be assumed to be an important factor in the evolution of coccinellid ITS1.