tbuckley/cabot-search huggingface dataset:
Abstract 1736: Is There An Indication For Transcoronary Ethanol VT Ablation In 2007?
Authors: Frederic Sacher, Piotr Sobieszcyk, Usha Tedrow, Andrew Einsenhower, Andrew Seldwyn, Jean-Marc Raymond, Bruce Koplan, Laurence Epstein, William Stevenson
Journal: Circulation (2007)

Introduction: TransCoronary Ethanol Ablation (TCEA) was proposed 15 years ago for incessant VTs resistant to any treatment (medications or ablation). However we sought to investigate whether this therapy could still be useful in the area of modern radiofrequency ablation. Methods: Eight patients (6 males, 55 ±7yo, 2.1 ±0.8 failed VT ablations) out of 586 VT ablation procedures underwent TCEA between 2000 and 2006. After identification of the artery supplying blood to the arrhythmogenic area, an angioplasty balloon was advanced in the artery then VT was induced and cooled saline infusion was performed distal to the balloon. If this did not interrupt VT another artery was targeted. If VT stopped, 1 to 5 ml of pure ethanol (96%) was injected. Results: All patients had scar related VT (septal:7, left inferior wall:1) with 4 pts having a non ischemic cardiomyopathy. Mean left ventricle ejection fraction prior to the procedure was 23 ±9%. In patients with septal scar, 1st and/or 2nd septal artery were targeted in 5 pts whereas for 2 this was not effective and a distal branch of the circumflex and the conus branch of the right coronary artery were targeted in 2. A branch of the posterior descending artery was targeted in the patient with inferior scar. Acute success was obtained in 5/8 (63%). Two patients experienced complications (transient cardiac stunning after ethanol infusion and delayed AV block). Twenty-four hours after the procedure, mean troponin Ic [0 – 0.1 ng/ml] and CPK-MB [0–5 ng/ml] were respectively 19.75 ±12.79 ng/ml and 121 ±108 ng/ml, mean ejection fraction was 18 ±8%(NS compared to before). With a mean follow-up of 29 ±23 months, 6/8 (75%) patients are still alive with no recurrence in 4 (50%). Conclusion: TCEA is an option in cases of refractory VT who fail radiofrequency ablation, especially in cases of septal scar.
Editorial: Long distance hyperthyroidism
Authors: H. T. Ricketts
Journal: JAMA (1976)

Not long ago, in these pages,<sup>1</sup>we mourned the descent of the pituitary gland as king of the endocrine realm. Mechanisms such as the releasing factors of the hypothalamus, the feedback safety valve, and the inhibitor somatostatin had preempted the signals that loosed its fruits or contained them. Now, it has been discovered that the pituitary has lost not its ability to govern the functions of the thyroid but its monopoly with respect to hyperthyroidism. The usurper is the hydatidiform mole, a benign neoplasm of the placenta that secretes human chorionic gonadotropin and has been found to be another thyroid-stimulating hormone (TSH). The first observation of this unlikely maker of thyrotropin was published by Tisné et al<sup>2</sup>in 1955, but it received little attention. In the 1960s, several investigators picked up the clue and redemonstrated the connection between the placental mole and hyperthyroidism. In 1969, Hershman and Starnes
AXL Mediates Cetuximab and Radiation Resistance Through Tyrosine 821 and the c-ABL Kinase Pathway in Head and Neck Cancer
Authors: Nellie K. McDaniel, Mari Iida, Kwangok P. Nickel, Colin A. Longhurst, Samantha R. Fischbach, Tamara S. Rodems, Carlene A. Kranjac, Amber Y. Bo, Qianyun Luo, Meghan M. Gallagher, Noah B. Welke, Kaitlyn R. Mitchell, Alison E. Schulz, Jaimee C. Eckers, Rong Hu, Ravi Salgia, Seungpyo Hong, Justine Y. Bruce, Randall J. Kimple, Deric L. Wheeler
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Radiation and cetuximab are therapeutics used in management of head and neck squamous cell carcinoma (HNSCC). Despite clinical success with these modalities, development of both intrinsic and acquired resistance is an emerging problem in the management of this disease. The purpose of this study was to investigate signaling of the receptor tyrosine kinase AXL in resistance to radiation and cetuximab treatment. Experimental Design: To study AXL signaling in the context of treatment-resistant HNSCC, we used patient-derived xenografts (PDXs) implanted into mice and evaluated the tumor response to AXL inhibition in combination with cetuximab or radiation treatment. To identify molecular mechanisms of how AXL signaling leads to resistance, three tyrosine residues of AXL (Y779, Y821, Y866) were mutated and examined for their sensitivity to cetuximab and/or radiation. Furthermore, reverse phase protein array (RPPA) was employed to analyze the proteomic architecture of signaling pathways in these genetically altered cell lines. Results: Treatment of cetuximab- and radiation-resistant PDXs with AXL inhibitor R428 was sufficient to overcome resistance. RPPA analysis revealed that such resistance emanates from signaling of tyrosine 821 of AXL via the tyrosine kinase c-ABL. In addition, inhibition of c-ABL signaling resensitized cells and tumors to cetuximab or radiotherapy even leading to complete tumor regression without recurrence in head and neck cancer models. Conclusions: Collectively, the studies presented herein suggest that tyrosine 821 of AXL mediates resistance to cetuximab by activation of c-ABL kinase in HNSCC and that targeting of both EGFR and c-ABL leads to a robust antitumor response.
The Architecture of Metabolism Maximizes Biosynthetic Diversity in the Largest Class of Fungi
Authors: Emile Gluck-Thaler, Sajeet Haridas, Manfred Binder, Igor V Grigoriev, Pedro W Crous, Joseph W Spatafora, Kathryn Bushley, Jason C Slot
Journal: Molecular Biology and Evolution (2020)

Abstract Ecological diversity in fungi is largely defined by metabolic traits, including the ability to produce secondary or “specialized” metabolites (SMs) that mediate interactions with other organisms. Fungal SM pathways are frequently encoded in biosynthetic gene clusters (BGCs), which facilitate the identification and characterization of metabolic pathways. Variation in BGC composition reflects the diversity of their SM products. Recent studies have documented surprising diversity of BGC repertoires among isolates of the same fungal species, yet little is known about how this population-level variation is inherited across macroevolutionary timescales. Here, we applied a novel linkage-based algorithm to reveal previously unexplored dimensions of diversity in BGC composition, distribution, and repertoire across 101 species of Dothideomycetes, which are considered the most phylogenetically diverse class of fungi and known to produce many SMs. We predicted both complementary and overlapping sets of clustered genes compared with existing methods and identified novel gene pairs that associate with known secondary metabolite genes. We found that variation among sets of BGCs in individual genomes is due to nonoverlapping BGC combinations and that several BGCs have biased ecological distributions, consistent with niche-specific selection. We observed that total BGC diversity scales linearly with increasing repertoire size, suggesting that secondary metabolites have little structural redundancy in individual fungi. We project that there is substantial unsampled BGC diversity across specific families of Dothideomycetes, which will provide a roadmap for future sampling efforts. Our approach and findings lend new insight into how BGC diversity is generated and maintained across an entire fungal taxonomic class.
Prevention of Ischemic Stroke
Authors: N H Shear, C Appel
Journal: New England Journal of Medicine (1995)

To the Editor: Smith et al. (Feb.9 issue) 1 report the use of transesophageal echocardiography to diagnose aortic trauma in a series of 121 patients at the University of Kentucky Medical Center over a 24-month period.The same authors have reported on two similar series in the past two years from the same institution. 2,3 The first article, by Kearney et al., describes a series of 69 patients followed for 18 months, and the second, by Buckmaster et al., a series of 160 patients followed for 33 months.The findings in these studies are similar and demonstrate the high sensitivity and specificity of transesophageal echocardiography for the detection of traumatic rupture of the aorta.The authors do not indicate in the most recent paper 1 whether these series were consecutive or whether, in fact, these studies all involve the same patients.From the methods described, it would appear that the latter may be the case.These are important studies, because they suggest that transesophageal echocardiography could replace aortography as the gold-standard investigation for aortic trauma.The conclusions of the papers will obviously be much stronger if the studies involved consecutive series with a total sample of 350 patients.We request that the authors describe more clearly the patients in these three series.
Topical 5-aminolaevulinic acid photodynamic therapy for extensive scalp actinic keratoses
Authors: T. Markham, P. Collins
Journal: British Journal of Dermatology (2008)

Scalp actinic keratoses (AKs) are common, particularly in elderly bald males. Cryotherapy and 5‐fluorouracil are effective for localized AKs but are limited in extensive disease. Topical 5‐aminolaevulinic acid photodynamic therapy (5‐ALA PDT) is an alternative. We treated four patients with extensive scalp AKs with low light dose, low dose‐rate topical 5‐ALA PDT using a broad‐spectrum visible light source. Three patients cleared and one showed significant improvement. Remission lasted 6 months.
Abstract 17582: Association Between Anatomical Situation Surrounding the Esophagus and the Prevalence of Transmural Thermal Injury After Pulmonary Vein Isolation With Cryoballoon Ablation
Authors: Yoshiyuki Matsumoto, Takashi Kaneshiro, Minoru Nodera, Masashi Kamioka, Hitoshi Suzuki, Akiomi Yoshihisa, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2017)

Background: Transmural thermal injury (TTI), such as esophageal erythema and periesophageal nerve injury leading to gastric hypomotility, is an important complication of pulmonary vein isolation (P...
RNA structural dynamics regulate early embryogenesis through controlling transcriptome fate and function
Authors: Boyang Shi, Jinsong Zhang, Jian Heng, Jing Gong, Ting Zhang, Pan Li, Bao-Fa Sun, Ying Yang, Ning Zhang, Yong-Liang Zhao, Hai-Lin Wang, Feng Liu, Qiangfeng Cliff Zhang, Yun-Gui Yang
Journal: Genome biology (2020)

Abstract Background Vertebrate early embryogenesis is initially directed by a set of maternal RNAs and proteins, yet the mechanisms controlling this program remain largely unknown. Recent transcriptome-wide studies on RNA structure have revealed its pervasive and crucial roles in RNA processing and functions, but whether and how RNA structure regulates the fate of the maternal transcriptome have yet to be determined. Results Here we establish the global map of four nucleotide-based mRNA structures by icSHAPE during zebrafish early embryogenesis. Strikingly, we observe that RNA structurally variable regions are enriched in the 3′ UTR and contain cis -regulatory elements important for maternal-to-zygotic transition (MZT). We find that the RNA-binding protein Elavl1a stabilizes maternal mRNAs by binding to the cis -elements. Conversely, RNA structure formation suppresses Elavl1a’s binding leading to the decay of its maternal targets. Conclusions Our study finds that RNA structurally variable regions are enriched in mRNA 3′ UTRs and contain cis -regulatory elements during zebrafish early embryogenesis. We reveal that Elavl1a regulates maternal RNA stability in an RNA structure-dependent fashion. Overall, our findings reveal a broad and fundamental role of RNA structure-based regulation in vertebrate early embryogenesis.
Methylation pattern of multiple genes in urine sediment DNA from bladder cancer cases and controls by high throughput quantitative methylation specific PCR (QMSP)
Authors: Mohammad O. Hoque, Shahnaz Begum, Ozlem Topaloglu, Aditi Chatterjee, Eli Rosenbaum, Wim Van Criekinge, William H. Westra, Mark P. Schoenberg, David Sidransky
Journal: Cancer Research (2005)

3150   Background: The early diagnosis of bladder cancer and the early detection of recurrence are central to effective treatment, as prognosis is directly related to the stage of disease. Promoter hypermethylation is now recognized as an important and common epigenetic pathway of gene inactivation. Because bladder cancer cells and DNA are shed into the urine, we sought to test the value of a quantitative methylation assay in urine sediment for the detection of bladder cancer. Methods: We examined primary tumor and matched urine DNA for aberrant methylation of nine gene promoters ( APC, ARF, CDH1, GSTP1, MGMT, p16, RAR-β2, Rassf1A  and  TIMP3 ) from 15 patients with bladder cancer by quantitative fluorogenic real-time PCR. We then tested an additional 160 urine sediment DNA samples (Total 175 urine) from bladder cancer patients of different stages and grades. 94 age-matched patients without any evidence of genitourinary cancer were used as a control. Result: In cases with matched tumor, the promoter methylation pattern found in urine matched the pattern in the primary tumors. 121 of 175(69%) patients with bladder cancer displayed methylation in at least one of four genes ( p16, ARF, MGMT  and  GSTP1 ), whereas all controls were negative for methylation at the established cut off (100% specificity). When we considered any one of these latter four genes and/or  RAR-β2  methylation, the sensitivity and specificity were 82% and 97% respectively (positive likelihood ratio 24.19 and negative likelihood ratio 0.19). Using established cut off values for all the nine genes, 85% sensitivity and 96% specificity was achieved with a positive and negative likelihood ratio of 18.97 and 0.16 respectively.  MGMT, ARF , and  TIMP3  methylation in urine correlated with primary tumor invasion and metastasis (p= ≤ 0.05, by logistic regression). The risk of death was statistically significantly higher in patients with  TIMP3  methylation (hazard ratio [HR] =1.97, 95% confidence interval [CI] =1.14 to 3.4; p= 0.01) than in patients without  TIMP3  methylation in urine. Conclusion: Testing a small panel of genes with the QMSP (Quantitative Methylation Specific PCR) assay in urine sediment DNA represents a powerful noninvasive approach for the detection of bladder cancer on a high throughput-automated platform. Methylation patterns in urine may also help predict the natural history of detected disease. Larger cohorts with longitudinal follow up will be required in future studies to define the impact of this technology on detection, prognosis and disease monitoring.
Medicines with one seller and many buyers: strategies to increase the power of the payer
Authors: Andrew Rintoul, Allison Colbert, Sarah Garner, Anita Kotwani, Sabine Vogler, Jacoline Bouvy, Andrew Hill
Journal: BMJ (2020)

Medicines with one seller and many buyers: strategies to increase the power of the payer Andrew Rintoul and colleagues argue that collaboration and transparency increase the market power of buyers who face a monopoly H ealth system budgets face increasing pressures from ageing populations, epidemiological transitions, and technological innovation.One area for buyers to find savings is in questioning whether the price they negotiate for a medicine is fair.This challenge of high prices is particularly acute for medicines that are available from a single source, where there is no alternative with a similar indication.Monopolies can use several techniques to consolidate their market power and maintain a high price. 1For example, they may emphasise slightly different indications of their medicine from those of competitors, marketing small differences in benefits and risks that may not be clinically meaningful.Health systems face consequences when markets fail because of a lack of competition: budgets need to increase, the needs of some patients are prioritised over others, out-of-pocket spending increases, and some patients do not receive treatment. 2-
Resiliency and Our Cardio-Oncology Community
Authors: Bonnie Ky, MD, MSCE, FACC
Journal: JACC CardioOncology (2020)

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Resiliency. If there is one quality that I hope for in my mentees, it is resiliency. Why? Because, as care providers in medicine, we have all experienced the sincere pain and the feelings of failure that come with loss—our patient who succumbed to a terrible metastatic
The Neandertal Progesterone Receptor
Authors: Hugo Zeberg, Janet Kelso, Svante Pääbo
Journal: Molecular Biology and Evolution (2020)

The hormone progesterone is important for preparing the uterine lining for egg implantation and for maintaining the early stages of pregnancy. The gene encoding the progesterone receptor (PGR) carries introgressed Neandertal haplotypes with two missense substitutions and a mobile Alu element. These Neandertal gene variants have reached nearly 20% frequency in non-Africans and have been associated with preterm birth. Here, we show that one of the missense substitutions appears fixed in Neandertals, while the other substitution as well as the Alu insertion were polymorphic among Neandertals. We show that two Neandertal haplotypes carrying the PGR gene entered the modern human population and that present-day carriers of the Neandertal haplotypes express higher levels of the receptor. In a cohort of present-day Britons, these carriers have more siblings, fewer miscarriages, and less bleeding during early pregnancy suggesting that the Neandertal progesterone receptor alleles promote fertility. This may explain their high frequency in modern human populations.
GLP-1 Receptor Signaling in Astrocytes Regulates Fatty Acid Oxidation, Mitochondrial Integrity, and Function
Authors: Katharina Timper, Almudena del Río-Martín, Anna Lena Cremer, Stephan Bremser, Jens Alber, Patrick Giavalisco, Luis Varela, Christian Heilinger, Hendrik Nolte, Aleksandra Trifunovic, Tamas L. Horvath, Peter Kloppenburg, Heiko Backes, Jens C. Brüning
Journal: Cell Metabolism (2020)

Astrocytes represent central regulators of brain glucose metabolism and neuronal function. They have recently been shown to adapt their function in response to alterations in nutritional state through responding to the energy state-sensing hormones leptin and insulin. Here, we demonstrate that glucagon-like peptide (GLP)-1 inhibits glucose uptake and promotes β-oxidation in cultured astrocytes. Conversely, postnatal GLP-1 receptor (GLP-1R) deletion in glial fibrillary acidic protein (GFAP)-expressing astrocytes impairs astrocyte mitochondrial integrity and activates an integrated stress response with enhanced fibroblast growth factor (FGF)21 production and increased brain glucose uptake. Accordingly, central neutralization of FGF21 or astrocyte-specific FGF21 inactivation abrogates the improvements in glucose tolerance and learning in mice lacking GLP-1R expression in astrocytes. Collectively, these experiments reveal a role for astrocyte GLP-1R signaling in maintaining mitochondrial integrity, and lack of GLP-1R signaling mounts an adaptive stress response resulting in an improvement of systemic glucose homeostasis and memory formation.
(13) Familial angio-oedema—C1 esterase inhibitor deficiency
Authors: M.J. Cheesbrough, P.D.C. Kinmont
Journal: British Journal of Dermatology (1978)

Journal Article (13) Familial angio‐oedema—C1 esterase inhibitor deficiency Get access M.J. Cheesbrough, M.J. Cheesbrough General Hospital, Nottingham Search for other works by this author on: Oxford Academic Google Scholar P.D.C. Kinmont P.D.C. Kinmont General Hospital, Nottingham Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 99, Issue s16, 1 December 1978, Pages 38–39, https://doi.org/10.1111/j.1365-2133.1978.tb15235.x Published: 01 December 1978
SETD5-Coordinated Chromatin Reprogramming Regulates Adaptive Resistance to Targeted Pancreatic Cancer Therapy
Authors: Zhentian Wang, Simone Hausmann, Ruitu Lyu, Tie-Mei Li, Shane M. Lofgren, Natasha M. Flores, Mary E. Fuentes, Marcello Caporicci, Ze Yang, Matthew Joseph Meiners, Marcus Adrian Cheek, Sarah Ann Howard, Lichao Zhang, Joshua Eric Elias, Michael P. Kim, Anirban Maitra, Huamin Wang, Michael Cory Bassik, Michael-Christopher Keogh, Julien Sage, Or Gozani, Pawel K. Mazur
Journal: Cancer Cell (2020)
Airway inflammation in COPD: physiological outcome measures and induced sputum
Authors: R.O. Crapo, R.L. Jensen, F.E. Hargreave
Journal: European Respiratory Journal (2003)

Chronic obstructive pulmonary disease (COPD) is a result of airway inflammation, and the best predictor of COPD is the early detection of airflow limitation by spirometry. The Global Initiative for Obstructive Lung Disease Workshop Report defines airflow limitation using simple spirometric indices. Available guidelines categorise the severity of COPD using forced expiratory volume in one second (FEV<sub>1</sub>) and forced vital capacity (FVC), with symptoms playing a minor role in the assessment. Current standards define COPD by progressive loss of FEV<sub>1</sub>, and thus longitudinal decline in FEV<sub>1</sub> will be the primary outcome variable for intervention studies aimed at preventing or reducing the loss of pulmonary function. There is evidence, however, that the variable FEV<sub>1</sub>/FVC and FEV<sub>1</sub> are often not measured properly in all settings. This article will discuss the roles of physiological measurements in diagnosing COPD and physiological outcome measures for COPD. It does not formally compare physiological measures with other outcome measures, such as symptoms or quality of life. Additionally, improved treatment of established disease requires a better understanding of the inflammatory process and its clinical effects and treatment. The inflammatory process, and how drugs affect it, can be studied noninvasively or relatively noninvasively by using refined methods of examining spontaneous or induced sputum. Enhanced understanding of the use of induced sputum will assist in predicting patients9 responses to short- and long-term inhaled corticosteroid treatment, and the methods of sputum examination need to be simplified so that they can be applied more easily to clinical practice.
144P Patient-reported outcomes (PROs) in advanced breast cancer (ABC) treated with ribociclib (RIB) + fulvestrant (FUL) as first-line (1L) and second-line (2L) therapy in MONALEESA-3 (ML-3)
Authors: P. Fasching, P. Neven, G. Jerusalem, J.T. Beck, A. Chan, M. De Laurentiis, G.V. Bianchi, M. Martin Jimenez, S. Chia, A. Gaur, M. Sondhi, K. Rodriguez-Lorenc, B. Lanoue, D. Chandiwana, A. Nusch
Journal: Annals of Oncology (2020)