tbuckley/cabot-search huggingface dataset:
Abstract 487: MicroRNA regulation of oral squamous cell carcinoma
Authors: Gary Guishan Xiao, Min Cao
Journal: Cancer Research (2018)

Abstract Oral squamous cell carcinoma (OSCC) remains the sixth most common human cancer with high mortality rate worldwide. Understanding the molecular mechanisms is important for development of an effective treatment for the disease. MicroRNA is a short, noncoded nucleotide playing an important role in tumorigenesis and metastasis. This study is to identify novel microRNAs and their targets in order to understand the molecular mechanisms underlying OSCC and metastasis using label-free proteomics and microRNA microarray techniques. Human oral tissue biopsies from three groups of subjects who had benign, localized carcinoma and distal carcinoma were collected from the archived tissue bank at Pathology in Creighton University. Total RNA and proteins were extracted from the core biopsy of the same subject. MicroRNA identification was performed by using Affymetrix GeneChip miRNA arrays and comprehensive data analysis. Protein was analyzed by using label-free LTQ orbit trap mass spectrometry. Forty-four miRNAs were upregulated significantly, including let-7b, miR-720, miR-21, and miR-1274b, while 41 miRNAs were remarkably downregulated, including miR-195, and miR-932, at localized and distal carcinoma compared to benign tissues. Additionally, as compared to benign, 38 miRNAs upregulated at local carcinoma were downregulated significantly at distal carcinoma, while other 17 miRNAs downregulated significantly at localized carcinoma were upregulated gigantically at distal carcinoma. Those miRNAs were further validated by qRT-PCR and FISH. Among those upregulated at both local and distal, miR-720 was further studied, and tryptase alpha-1 as its target was identified. MicroRNA-720 mimics suppressed significantly the expression of tryptase alpha-1 in cultured human OSCC stem cell lines. Results from miR-720 tissue microarray analysis showed that 98.8% of sensitivity and 100% of specificity for OSCC detection were achieved, suggesting that miR-720 may be developed as a novel biomarker for detection of human OSCC. Citation Format: Gary Guishan Xiao, Min Cao. MicroRNA regulation of oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 487.
Long-term Consequences of Kawasaki Disease
Authors: HirohisaKato, TetsuSugimura, TeijiAkagi, NoboruSato, KanokoHashino, YasukiMaeno, TakeyoKazue, GenzyuEto, RumiYamakawa
Journal: Circulation (1996)

Background The long-term consequences of the cardiovascular sequelae in Kawasaki disease remain uncertain. Methods and Results We identified 594 consecutive children with acute Kawasaki disease between 1973 and 1983, and this cohort was followed up for 10 to 21 years (mean, 13.6 years). In all patients, we evaluated coronary lesions by coronary angiography just after the acute stage. One hundred and forty-six patients (24.6%) were diagnosed as having coronary aneurysms. A second angiogram was performed 1 to 2 years later in all 146 patients who previously had coronary aneurysms, which demonstrated that 72 (49.3%) of these 146 had regression in the coronary aneurysm. A third angiogram was performed for 62 patients, a fourth for 29, and a fifth for 17. By 10 to 21 years after the onset of the illness, stenosis in the coronary aneurysm had developed in 28 patients. Myocardial infarction occurred in 11 patients, 5 of whom died. In the 26 patients with giant coronary aneurysms, stenotic lesions developed in 12...
Laparoscopic Transabdominal Adrenalectomy—A Procedure That Has Stood the Test of Time
Authors: Masha J. Livhits, Michael W. Yeh
Journal: JAMA Surgery (2018)

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Abstract 11449: Influence of Exonic Variation on Heparin-Induced Thrombocytopenia
Authors: Jason H Karnes, Joshua C Denny, Robert M Cronin, Christian M Shaffer, Erica A Bowton, James D Cowan, Jonathan D Mosley, Sara L Van Driest, Peter E Weeke, Quinn S Wells, Dan M Roden
Journal: Circulation (2014)

Introduction: Heparin-induced thrombocytopenia (HIT) is an immune-mediated, potentially fatal adverse effect of heparin treatment. Here we test the hypotheses that exonic variants are associated wi...
Abstract 10864: Effect of Fructose vs Sucrose and Sucralose on Glucose, Insulin and Triglyceride Levels in a Solid Mixed Meal in Healthy People
Authors: Clare Gallagher, Peter Clifton, Eva Pedersen, Jennifer Keogh
Journal: Circulation (2015)

Background: Fructose, a nutritive sweetener with a low GI has been shown in previous studies to elevate TGs when compared to a glucose control. There is limited data available on the effect of fructose in a mixed meal. The aim of this study was to determine the effects of sucrose, fructose and sucralose on triglyceride, glucose and insulin response in an acute study in healthy individuals. Methods: This study was a randomised cross-over design. Twenty-seven participants with a median age of 40, and a BMI of 26.3kg/m2 completed the study. Fructose (52g), sucrose (65g) and Sucralose (6g of Splenda) were delivered as sweet taste-balanced muffins with a standardised fat load (66g). Blood samples were taken at baseline and every 30 minutes for 4 hours. Glucose, triglyceride and insulin concentrations over time, area under the curve (AUC) and incremental area under the curve (iAUC) were analysed. Results: No significant difference was found between the three sweeteners for triglyceride and glucose concentrations, AUC and iAUC. A significant difference was found for insulin treatment (p = 0.001), time*treatment (p = 0.035), AUC (p =0.000) and iAUC (p =0.000). Post hoc analysis showed that fructose had a significantly lower response than either sucrose (p = 0.006) or sucralose (p = 0.041). Conclusion: Fructose at a moderate dose did not significantly elevate triglycerides in comparison to sucrose or sucralose. No significant difference in the glycaemic response between the meals was found. These results indicate that these sweeteners can be safely interchanged for normal mixed meals. Fructose showed a lower insulin response which may be beneficial long-term in those at risk of type 2 diabetes.
Cumulative antibiotic use and efficacy of immune checkpoint inhibitors in patients with advanced cancer.
Authors: Nadina Tinsley, Cong Zhou, Shaun Villa, Grace Tan, Paul Lorigan, Fiona Helen Blackhall, Tony Elliott, Matthew Krebs, Louise Carter, Fiona Thistlethwaite, Andrew Hughes, Natalie Cook
Journal: Journal of Clinical Oncology (2018)

3010 Background: Efficacy of immune checkpoint inhibitors (CKIs) for treatment of cancer may be affected by the use of antibiotics (ABX). The gut microbiome is involved in immunotherapy responses therefore ABX known to alter the gut microbiome may affect tumour inflammation and microenvironment, leading to decreased CKI efficacy. Methods: Retrospective data analysis was undertaken on metastatic cancer patients (pts) treated with CKIs between January 2015 and March 2017 at the Christie NHS Foundation Trust. Melanoma, renal and non-small cell lung cancer (NSCLC) pts were included. Demographics, prior systemic treatment, extent of disease, CKI agent and use of ABX (route, duration, multiple concurrent/successive courses) were collected. Progression free survival (PFS) and overall survival (OS) were compared between ABX groups (ABX + defined as pts treated with ABX within 2 weeks of CKI initiation or 6 weeks after, ABX – as pts with no ABX during specified period). Statistical analyses were performed with univariate and multivariate models. Results: Of 303 included pts (201 (66%) melanoma, 56 (18%) NSCLC and 46 (15%) renal) 94 (31%) received ABX (commonest beta-lactam ABX and macrolides). In multivariate analysis, ABX + pts had shorter PFS and OS when compared to ABX – pts: PFS 97 days (95% CI 84-122) vs 178 days (95% CI 155-304) p = 0.049; OS 317 days (95% CI 221-584) vs 651 days (95% CI 477-998) p = 0.001. Cumulative ABX ( > 10 days, multiple concurrent/successive courses) demonstrated particularly shortened PFS 87 days (95% CI 83-122) p = 0.0093 and OS 193 days (95% CI 96-355) p = 0.00021. Pts treated with ABX prior to CKI initiation had shorter PFS and OS than those treated after CKI initiation (HR 1.37 and HR 1.72) p = 0.29 and 0.08 respectively. Conclusions: To our knowledge, this is the largest multivariate analysis showing ABX use is an independent predictor of shorter PFS and OS in cancer pts treated with CKI. It is the first analysis to demonstrate cumulative ABX use is associated with even poorer outcomes across multiple tumour types independent of clinical factors. The data suggests a trend towards reduced PFS in pts who received ABX prior to CKI initiation, warranting further validation in a larger cohort.
Abstract 2311: Determinants of CDK4 target engagement by palbociclib, ribociclib and abemaciclib
Authors: Jennifer L. Green, Tyzoon Nomanbhoy
Journal: Cancer Research (2018)

Abstract Palbociclib, ribociclib and abemaciclib compose a class of ATP-competitive CDK4 and CDK6 inhibitors that have demonstrated preclinical and clinical efficacy against various tumor types. While these inhibitors have favorably altered the landscape of cancer therapeutics, identification of patients likely to respond to CDK4/6 inhibition remains a challenge. Previously, we used our chemoproteomics platform (KiNativ), which measures competition of an ATP- or ADP-acyl-phosphate probe, to profile lysates generated from cells that were treated with palbociclib. We showed that palbociclib-CDK4 target engagement is cell line specific and that engagement correlates with sensitivity of the cell line to palbociclib-mediated growth inhibition. However, the circumstances that determine whether target engagement is achieved were not understood. In an effort to understand the molecular mechanisms that influence CDK4 target engagement, we used the same proteomics platform to interrogate the contribution of various known CDK regulators. We identified a family of proteins that prevents palbociclib target engagement upon overexpression and whose lack of expression correlates with palbociclib sensitivity. This interaction is specific for CDK4/6 as modulation of the drug's interaction with off-target kinases was not affected by overexpression of these proteins. Furthermore, we found that these proteins similarly prevent CDK4 target engagement by ribociclib and abemaciclib. Incorporation of the proteins identified here into a biomarker strategy should help to enrich for patients likely to respond to CDK4/6 inhibition therapy and expand the utility of these inhibitors. Citation Format: Jennifer L. Green, Tyzoon Nomanbhoy. Determinants of CDK4 target engagement by palbociclib, ribociclib and abemaciclib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2311.
BMA negotiator calls for more male medical students
Authors: S. Walker
Journal: BMJ (2002)

Unhappy doctors Medical education must reassert its claim to academic high groundEditor-Ham and Alberti place the current crisis in medicine in context. 1 Let us hope that the public, the profession, and the government can rise to the challenges that they laid down.They showed remarkable restraint in describing the politicisation of the NHS, but I was surprised that they did not emphasise the crucial importance of medical education and the role of our medical schools in understanding what is going wrong with medicine.The General Medical Council has repeatedly called for radical reforms of the curriculums in undergraduate medicine, some of which have now been implemented.But whether our medical schools can instil the personal attributes and professional attitudes that are necessary for graduating students to engage with the complex sociopolitical agenda described by Ham and Alberti is less clear.The teaching and assessment of attitudes is a real challenge, but if we continue to rely on role modelling then medical education will remain hopelessly out of step with the changes taking place in society and the profession.Medical schools have a crucial role in preparing their students for participation in the new compact described by Ham and Alberti.In an attempt to bolster a reduced and demoralised medical workforce in the United Kingdom new medical schools are being opened and student numbers increased in the old ones.At the same time higher education funding is being squeezed as never before.Many established medical schools are reeling from the financial consequences of the 2001 research assessment exercise.Staffing cuts are inevitable, and many will probably fall on clinical academics, who give most to undergraduate education; those who work for research deans obsessed by their ratings in the research assessment exercise, however, will probably be spared.It must be a matter of public concern that higher education funding streams to support undergraduate medical education are being diverted to prop up faltering research enterprises.Medical education now needs to reassert its claim to the academic high ground in our medical schools, on which so much depends.
Abstract 1800: Progesterone receptor attenuates STAT1-mediated interferon signaling in breast cancer
Authors: Merit Goodman, Gloria Trinca, Katherine Walter, Evangelia Papachristou, Clive D'Santos, Tianbao Li, Qi Liu, Zhao Lai, Prabhakar Chalise, Rashna Madan, Victor Jin, Jason Carroll, Christy Hagan
Journal: Cancer Research (2018)

Abstract Why some tumors remain indolent and others progress to clinical relevance remains a major unanswered question in cancer biology. Interferon signaling in nascent tumors, mediated by STAT1, is a critical step through which the surveilling immune system can recognize and destroy developing tumors, thereby blocking their progression. We used an unbiased approach aimed at identifying nuclear protein interactions, called RIME, to identify novel progesterone receptor (PR) protein-protein interactions in T47D breast cancer cells. Using this technique, we identified a novel interaction between PR and STAT1. This interaction led to decreased interferon-induced STAT1 phosphorylation, a phenotype that was further potentiated in the presence of PR ligand. In human breast cancer samples, PR-positive tumors exhibited lower levels of phospho-STAT1 as compared to their PR-negative counterparts, indicating that this phenotype translates to human tumors. Breast cancer cells lacking PR expression exhibited higher levels of interferon-stimulated gene (ISG) RNA, the transcriptional endpoint of interferon activation, indicating that unliganded PR alone could decrease transcription of ISGs. Moreover, the absence of PR led to increased recruitment of STAT1, STAT2 and IRF9 (key transcription factors necessary for ISG transcription) to ISG promoters. These data indicate that PR, both in the presence and absence of ligand, attenuates interferon-induced STAT1 signaling, culminating in significantly abrogated activation of genes transcribed in response to interferons. PR-positive tumors may use downregulation of STAT1-mediated interferon signaling to escape immune surveillance, leading to the development of clinically relevant PR-positive tumors. Selective immune evasion of PR-positive tumors may be one explanation as to why over 70% of breast cancers are PR-positive at the time of diagnosis. Citation Format: Merit Goodman, Gloria Trinca, Katherine Walter, Evangelia Papachristou, Clive D'Santos, Tianbao Li, Qi Liu, Zhao Lai, Prabhakar Chalise, Rashna Madan, Victor Jin, Jason Carroll, Christy Hagan. Progesterone receptor attenuates STAT1-mediated interferon signaling in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1800.
Responses of the Sino-atrial Node to Change in Pressure in the Sinus Node Artery
Authors: Korokuhashimoto, Shigeotanaka, Minoruhirata, Shigeotoshichiba
Journal: Circulation Research (1967)

The sino-atrial node area was perfused selectively through the right atrial artery in 76 dogs. The relationship between changes in the blood pressure in this artery and sinus node rhythmicity was studied in 56 hearts in which the major blood supply to the sinus node artery came from the right atrial artery. A reciprocal relation was observed between changes of blood pressure in the sinus node artery and the sinus rate. Some characteristics were: (1) The negative chronotropic effect induced by raising the blood pressure was linearly related to the Degrees of pressure change and more prominent than the positive chronotropic effect induced by reducing the pressure. (2) This relationship was most prominent in a limited range between 20 and 100 mm Hg. (3) Dichloroisoproterenol, atropine, hexamethonium, reserpine and vagotomy did not modify these responses. It is concluded that this localized mechanosensitivity of the sinus node to changes in arterial pressure may be responsible for the regulation of the heart ...
Heterogeneity in Lung <sup>18</sup> FDG Uptake in Pulmonary Arterial Hypertension
Authors: Lan Zhao, Ali Ashek, Lei Wang, Wei Fang, Swati Dabral, Olivier Dubois, John Cupitt, Soni Savai Pullamsetti, Emanuele Cotroneo, Hazel Jones, Gianpaolo Tomasi, Quang-De Nguyen, Eric O. Aboagye, Mona A. El-Bahrawy, Gareth Barnes, Luke S. Howard, J. Simon R. Gibbs, Willy Gsell, Jian-Guo He, Martin R. Wilkins
Journal: Circulation (2013)

Pulmonary arterial hypertension (PAH) is a disease of progressive vascular remodeling, characterized by dysregulated growth of pulmonary vascular cells and inflammation. A prevailing view is that abnormal cellular metabolism, notably aerobic glycolysis that increases glucose demand, underlies the pathogenesis of PAH. Increased lung glucose uptake has been reported in animal models. Few data exist from patients with PAH.Dynamic positron emission tomography imaging with fluorine-18-labeled 2-fluoro-2-deoxyglucose ((18)FDG) ligand with kinetic analysis demonstrated increased mean lung parenchymal uptake in 20 patients with PAH, 18 with idiopathic PAH (IPAH) (FDG score: 3.27±1.22), and 2 patients with connective tissue disease (5.07 and 7.11) compared with controls (2.02±0.71; P<0.05). Further compartment analysis confirmed increased lung glucose metabolism in IPAH. Lung (18)FDG uptake and metabolism varied within the IPAH population and within the lungs of individual patients, consistent with the recognized heterogeneity of vascular pathology in this disease. The monocrotaline rat PAH model also showed increased lung (18)FDG uptake, which was reduced along with improvements in vascular pathology after treatment with dicholoroacetate and 2 tyrosine kinase inhibitors, imatinib and sunitinib. Hyperproliferative pulmonary vascular fibroblasts isolated from IPAH patients exhibited upregulated glycolytic gene expression, along with increased cellular (18)FDG uptake; both were reduced by dicholoroacetate and imatinib.Some patients with IPAH exhibit increased lung (18)FDG uptake. (18)FDG positron emission tomography imaging is a tool to investigate the molecular pathology of PAH and its response to treatment.
Abstract 18972: Are Three Weeks of Oral Anticoagulation Necessary in Patients With Paroxysmal AF Undergoing Ablation With Uninterrupted NOACs?
Authors: Luigi Di Biase, David Briceno, Chintan Trivedi, Sanghamitra Mohanty, Carola Gianni, Rodney Horton, J. David Burkhardt, Javier Sanchez, G. Joseph Gallinghouse, Shane Bailey, Jason Zagrodzky, Amin Al-Ahmad, Patrick Hranitzky, Salwa Beheiry, Richard Hongo, Dhanunjaya Lakkireddy, Andrea Natale
Journal: Circulation (2016)

Background: The duration of pre-procedure anticoagulation before AF ablation with the use of uninterrupted non vitamin K antagonist (NOACs) is unclear in the literature. Hypothesis: We sought to ev...
Flow Through Collapsible Tubes: Augmented Flow Produced by Resistance at the Outlet
Authors: Simonrodbard
Journal: Circulation (1955)

The physical laws describing the character of flow through blood vessels may depart radically from those which have been developed by engineers and physicists for uniform flow through rigid tubes of uniform diameter. These deviations are marked in the case of flow through collapsible tubes,such as blood vessels and valves. At critically high velocities, the flow pattern may be transformed from a quiet, uniform smooth-flowing stream to an interrupted series of jets with the production of audible sound and with marked energy losses. The present study deals primarily with the paradoxically increased flow which may take place through collapsible tubes when a resistance is added to the outlet from the system. This marked deviation from the laws for rigid tubes is attributed to the vessel-distending effects of the added resistance, and to the inhibition of the phenomenon of recurrent collapsibility. The present in vitro experiments are used to attempt to explain certain paradoxical findings in flow through th...