tbuckley/cabot-search huggingface dataset:
Abstract 1532: Exome and transcriptome profiling of lung adenocarcinoma in female never-smokers
Authors: Sanghyuk Lee, Pora Kim, Yukyung Jun, Charny Park, Suyeon Kim, Hee-Young Lee, Juhee Keum, Yeonhwa Jung, Yeonjoo Jung, Chaehwa Seo, Kyoohyoung Rho, Jong-Eun Lee, Wankyu Kim, Jaesang Kim, Jhingook Kim
Journal: Cancer Research (2014)

Abstract Background: Lung cancer is the leading cause of cancer-related mortality in the world. TCGA projects for lung adenocarcinoma and squamous cell carcinoma are the largest datasets publicly available so far. They include diverse subtypes and population groups and thus small population groups such as female never-smokers in Asian are under-represented. Female never-smokers are an important population cohort where mutations due to genetic factors are enriched rather than environmental factors such as smoking. We applied the high throughput deep sequencing strategy to catalog somatic mutations and to profile gene expression levels for Korean patients. Results: Deep sequencing data of exome and transcriptome were generated for tumor and matched normal tissues from 100 non-small-cell lung cancer (NSCLC) patients in female never-smokers. The mutational catalogue includes numerous somatic mutations, indels, and gene-fusion events. Comparison with TCGA lung cancer data shows that our patients harbor much less and homogeneous somatic mutations as expected. Mutational frequency and driver gene analyses identified many novel candidates of causal genetic variations. For example, our mutation spectrum reveals 5 key modules of enriched somatic mutations such as EGFR, p53, Wnt signaling pathways, ECM organization, and cell cycle checkpoints. Furthermore, network analysis of integrating mutation and expression data illustrates the detailed mechanism of dysregulation in tumorigenesis of lung adenocarcinoma. Conclusion: Our study elucidates clinically important mutations and regulatory elements in NSCLC. It is expected that our dataset would serve as an important resource for lung cancer research especially in Asian populations. Citation Format: Sanghyuk Lee, Pora Kim, Yukyung Jun, Charny Park, Suyeon Kim, Hee-Young Lee, Juhee Keum, Yeonhwa Jung, Yeonjoo Jung, Chaehwa Seo, Kyoohyoung Rho, Jong-Eun Lee, Wankyu Kim, Jaesang Kim, Jhingook Kim. Exome and transcriptome profiling of lung adenocarcinoma in female never-smokers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1532. doi:10.1158/1538-7445.AM2014-1532
Photosensitive mycosis fungoides or actinic reticuloid?
Authors: B.D. De Silva, K. Mclaren, G.M. Kavanagh
Journal: British Journal of Dermatology (2000)

Abstract We report two patients who satisfied the diagnostic criteria for actinic reticuloid (AR) on initial presentation, in whom genotypic analysis of early skin biopsies failed to show T-cell gene receptor rearrangements. Both patients progressed to widespread skin involvement associated with histopathological and genotypic features of mycosis fungoides (MF). Arguably, these patients may have had photosensitive MF from the outset, but their clinical features, phototesting, and subsequent demonstration of a T-cell gene receptor rearrangement in the skin could also suggest progression of AR to MF.
Abstract 1454: Differentiated Cardiomyocytes Divide in Response to Neuregulin1 by Disassembling The Contractile Apparatus
Authors: Bernhard Kuhn, Kevin Bersell, Salvatore Mancarella, Shima Arab
Journal: Circulation (2008)

Introduction: Cardiomyocytes carry the pump function of the heart. What molecular and cellular mechanisms control proliferation of cardiomyocytes is an unresolved question with high impact on regenerative medicine. Hypothesis: The growth factor neuregulin1 (NRG1) and its tyrosine kinase receptor ErbB4 control cardiomyocyte proliferation during prenatal development. NRG1 and ErbB4 are expressed in the adult heart. We hypothesized that activating NRG1 signaling stimulates cell cycle reentry and division of a subpopulation of differentiated cardiomyocytes. Methods: We determined cardiomyocyte cell cycle reentry and division in vitro using immunofluorescence microscopy and live cell imaging as read-out assays. We tested the in vivo proliferative effect of controlling NRG1 signaling at the level of its receptor using inducible cardiomyocyte-specific ErbB4 knockout mice and ErbB4 transgenic mice. Results: NRG1 induced cell cycle reentry of large, striated, and rod-shaped cardiomyocytes that express cardiac contractile proteins, consistent with a differentiated phenotype. Live cell imaging demonstrated in real time that NRG1 induces differentiated cardiomyocytes to undergo karyokinesis (nuclear division) and cytokinesis (cytoplasmic division), followed by separation into two differentiated daughter cardiomyocytes. During cell division, cardiomyocytes disassembled their contractile fibrils in the regions of the mitotic spindle and the cleavage furrow. NRG1 induced karyokinesis in 33% of mononucleated and in 1% of binucleated cardiomyocytes. Mononucleated cardiomyocytes completed cytokinesis, while binucleated cardiomyocytes did not. In vivo, postnatal genetic inactivation of the NRG1 receptor ErbB4 reduced cycling of differentiated mononucleated cardiomyocytes (Ctr. 5% vs. ko 0%, P &lt; 0.01). In contrast, transgenic expression of ErbB4 increased cycling of differentiated mononucleated cardiomyocytes (Ctr. 7.2% vs. tg 22.6%, P &lt; 0.05). Conclusions: ErbB4 is required and NRG1 and ErbB4 are sufficient to induce proliferation of a subpopulation of differentiated cardiomyocytes. NRG1 and the pathway that it regulates may provide new therapeutic targets to enhance mammalian cardiac regeneration. This research has received full or partial funding support from the American Heart Association, AHA Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).
Harnessing endogenous pathways and metabolites to treat or prevent neurodegenerative disease
Authors: Todd E Golde, Kevin Felsenstein, Paramita Chakrabarty, Andy Li, Brenda Moore, Jung Joo In, Pedor Cruz, Ashely Price, David Borchelt, Christopher Janus, Carolina Cebballos-Diaz, Awilda Rosario
Journal: Molecular Neurodegeneration (2013)

As the field moves towards earlier interventions in preclinical stages of AD or even envisions true primary prevention strategies, the therapeutic strategies employed must be “safe enough”. Whether any current therapeutic (e.g., β-secretase inhibitors, γ-secretase modulators (GSM) or anti-Aβ immunotherapies) being tested for disease modification is sufficiently safe is not known. In order to try and identify “safe enough” therapeutics, we have been evaluating whether endogenous regulators of Aβ can be harnessed as therapeutics. We have identified a cholesterol metabolite, cholestenoic acid (CA), as potent GSM, and have genetic data from mice that are consistent with a role for CA in regulating Aβ42 levels in the brain. We will discuss our ongoing studies exploring how we might utilize CA or the CA metabolic pathway to safely lower Aβ42 levels. In addition, we have been evaluating how we can use soluble forms of endogenous innate immune receptors to alter Aβ deposition and modulate neuroinflammation in mouse models of AD. We have also been exploring the utility of such strategy in other neurodegenerative models. Effects of soluble toll-like receptors and soluble TREM2 will be presented. Our current data establish that soluble TLR4 and 5 both dramatically inhibit Aβ deposition but that soluble TLR2 and 6 do not. We also have data that suggest the utility of these soluble receptors in α-synucleinopathies. By using endogenous metabolites and receptors, we hope that the likelihood of adverse toxicities will be diminished and that these or endogenous factors can be safely developed for prophylactic or early intervention in AD and perhaps other neurodegenerative disorders.
Inflation pressures are associated with outcomes in ventilated patients after lung transplantation
Authors: Louit Thakuria, Rosada Davey, Rosalba Romano, Martin Carby, Sundeep Kaul, Mark Griffiths, Andre Simon, Anna Reed, Nandor Marczin
Journal: European Respiratory Journal (2014)

Introduction   The injurious effects of large tidal volumes during mechanical ventilation in ARDS are well established, but the impact and determinants of injurious ventilation in lung transplantation are unknown.   Methods   124 bilateral lung transplants between June 2010 and April 2013 were reviewed. Patients were retrospectively assigned to high (≥25cm H 2 O) and low pressure ( 2 O) groups based on the average inflation pressures used in the first 6 hours after surgery. Average tidal volumes and lung compliance were also recorded. The median values [with interquartile ranges] for ICU length of stay (LOS) and lung function (% predicted FEV 1  at 3 months) were documented for each group. The 6 month survival rate was also recorded.   Results   The low-pressure group (n=76) had a LOS of 5 days [4-19], FEV 1  of 79.2% [62.7-92.6] and 6 month survival rate of 95%. The high-pressure group (n=48) had a prolonged LOS of 12 days ([4-36], p=0.012), a lower FEV 1  at 61.4% ([51.3-67.0], p 2 O, [28-39]) than the high pressure group (24ml/cmH 2 O, [20-27], p   Discussion   Reduced lung compliance and mechanical ventilation with high inflation pressures in the first hours following lung transplantation are significantly associated with poorer outcomes for months after surgery. This may reflect early lung injury necessitating the use of higher inflation pressures. Alternatively, ventilation with higher inflation pressures might have inflicted lung injury that adversely affected clinical outcomes.
P-Q-R-S-T. A Guide to Electrocardiogram Interpretation.
Authors: Joseph E. F. Riseman
Journal: Annals of Internal Medicine (1969)

The demand for a simple presentation of electrocardiography suitable for the beginner has led to the publication of a number of compends. The present volume, which has gone into a second edition within three years, is among the best. Of course it has all the faults, as the author recognizes, that come with an attempt to condense a large mass of data into a small space. The text is illustrated with diagrams, some of which are inaccurate, e. g. that on auricular flutter on page 19, that on digitalis T waves on page 41 and the chest lead of left and right heart strain on page 55. It is regrettable that the author suggests that the electrocardiogram may be taken on a seated patient. It is an error to consider that an ST depression of any extent in the chest leads is normal; it is also an error to consider
The JNC 7 Hypertension GuidelinesThe JNC 7 Hypertension Guidelines
Authors: Hean Teik Ong
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Implantable Chip Approved
Authors: Tracy Hampton
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Negative predictive value of skin tests to neuromuscular blocking agents
Authors: L. F. Ramirez, A. Pereira, A. M. Chiriac, M.‐C. Bonnet‐Boyer, P. Demoly
Journal: Allergy (2011)

To cite this article: Ramirez LF, Pereira A, Chiriac AM, Bonnet‐Boyer M‐C, Demoly P. Negative predictive value of skin tests to neuromuscular blocking agents. Allergy 2012; 67: 439–441. Abstract Allergy to neuromuscular blocking agents (NMBAs) is the most important caue of perioperative anaphylaxis in France. The diagnosis relies on a careful clinical history, the search of serum IgE antibodies, and the realization of skin tests. Although the skin tests are the most important tool and their sensitivity is widely recognized, the lack of information about their negative predictive value represents an important issue in the management of patients who require a new procedure with NMBA injection. We present a series of 49 patients with confirmed allergy to NMBAs, six of whom required a subsequent surgery with neuromuscular blockade. Negative skin tests allowed the selection of an alternative NMBA, which was well tolerated in all 6 cases. We found an excellent negative predictive value of skin tests in our series but larger studies are required to properly address this question.
A Clinical Trial Comparing Primary Coronary Angioplasty with Tissue Plasminogen Activator for Acute Myocardial Infarction
Authors: Maarten Simoons, Stephen Ellis
Journal: New England Journal of Medicine (1997)

Among physicians who treat patients with acute myocardial infarction, there is controversy about the magnitude of the clinical benefit of primary (i.e., immediate) coronary angioplasty as compared with thrombolytic therapy.
Managing Family Planning in General Practice, by Sam Rowlands
Authors: T. Carney
Journal: BMJ (1997)

Football is a global game which is constantly evolving, showing substantial increases in physical and technical demands. Nutrition plays a valuable integrated role in optimising performance of elite players during training and match-play, and maintaining their overall health throughout the season. An evidence-based approach to nutrition emphasising, a ‘food first’ philosophy (ie, food over supplements), is fundamental to ensure effective player support. This requires relevant scientific evidence to be applied according to the constraints of what is practical and feasible in the football setting. The science underpinning sports nutrition is evolving fast, and practitioners must be alert to new developments. In response to these developments, the Union of European Football Associations (UEFA) has gathered experts in applied sports nutrition research as well as practitioners working with elite football clubs and national associations/federations to issue an expert statement on a range of topics relevant to elite football nutrition: (1) match day nutrition, (2) training day nutrition, (3) body composition, (4) stressful environments and travel, (5) cultural diversity and dietary considerations, (6) dietary supplements, (7) rehabilitation, (8) referees and (9) junior high-level players. The expert group provide a narrative synthesis of the scientific background relating to these topics based on their knowledge and experience of the scientific research literature, as well as practical experience of applying knowledge within an elite sports setting. Our intention is to provide readers with content to help drive their own practical recommendations. In addition, to provide guidance to applied researchers where to focus future efforts.
762. Human Papillomavirus Type 16 Helper Functions for Adeno-Associated Virus Type 2 Replication
Authors: Paul L. Hermonat, Yong Liu, Jawahar L. Mehta, Hong You
Journal: Molecular Therapy (2004)

Top of pageAbstract
Human papillomavirus (HPV) is known to “help” adeno-associated virus (AAV) to replicate to high levels during skin co-infection. However, unlike AAV's other helper viruses adenovirus and herpes simplex, very little is known about the HPV genes which help AAV. In this study we surveyed four HPV-16 early genes, E1, E2, E6, and E7, for their ability to increase the basal level of AAV replication in a stratifying squamous epithelium. It was found that the HPV-16 E1, E2, and E6 genes were able to stimulate higher AAV replication in keratinocytes cultures upon co-transfection during wild type AAV-2 infection. E1 had the strongest enhancing effect upon AAV DNA replication (Southern blot), RNA expression (RT-PCR), protein expression (Western blot) and AAV virion production (2 plate-Southern blot). Further study of partial E1 sequence mutants showed that the carboxy-half of E1, the helicase/ATPase domain, was the main contributor to HPV E1 helper activity. These latter data suggest that helicase activity may be E1's mechanism of action for helping AAV replication. These data are important for understanding the HPV-AAV interaction and its effect on cervical cancer risk. These data are also important as HPV helper genes may be potentially useful in generating recombinant AAV virions for gene therapy purposes as the adenovirus and herpes virus genes are now used.
Fixed-Dose Combination Therapy With Daclatasvir, Asunaprevir, and Beclabuvir for Noncirrhotic Patients With HCV Genotype 1 Infection
Authors: Fred Poordad, William Sievert, Lindsay Mollison, Michael Bennett, Edmund Tse, Norbert Bräu, James Levin, Thomas Sepe, Samuel S. Lee, Peter Angus, Brian Conway, Stanislas Pol, Nathalie Boyer, Jean-Pierre Bronowicki, Ira Jacobson, Andrew J. Muir, K. Rajender Reddy, Edward Tam, Grisell Ortiz-Lasanta, Victor de Lédinghen, Mark Sulkowski, Navdeep Boparai, Fiona McPhee, Eric Hughes, E. Scott Swenson, Philip D. Yin
Journal: JAMA (2015)

<h3>Importance</h3> The antiviral activity of all-oral, ribavirin-free, direct-acting antiviral regimens requires evaluation in patients with chronic hepatitis C virus (HCV) infection. <h3>Objective</h3> To determine the rates of sustained virologic response (SVR) in patients receiving the 3-drug combination of daclatasvir (a pan-genotypic NS5A inhibitor), asunaprevir (an NS3 protease inhibitor), and beclabuvir (a nonnucleoside NS5B inhibitor). <h3>Design, Setting, and Participants</h3> This was an open-label, single-group, uncontrolled international study (UNITY-1) conducted at 66 sites in the United States, Canada, France, and Australia between December 2013 and August 2014. Patients without cirrhosis who were either treatment-naive (n = 312) or treatment-experienced (n = 103) and had chronic HCV genotype 1 infection were included. <h3>Interventions</h3> Patients received a twice-daily fixed-dose combination of daclatasvir, 30 mg; asunaprevir, 200 mg; and beclabuvir, 75 mg. <h3>Main Outcomes and Measures</h3> The primary study outcome was SVR12 (HCV-RNA &lt;25 IU/mL at posttreatment week 12) in patients naive to treatment. A key secondary outcome was SVR12 in the treatment-experienced cohort. <h3>Results</h3> Baseline characteristics were comparable between the treatment-naive and treatment-experienced cohorts. Patients were 58% male, 26% had<i>IL28B</i>(rs12979860) CC genotype, 73% were infected with genotype 1a, and 27% were infected with genotype 1b. Overall, SVR12 was observed in 379 of 415 patients (91.3%; 95% CI, 88.6%-94.0%): 287 of 312 treatment-naive patients (92.0%; 95% CI, 89.0%-95.0%) and 92 of 103 treatment-experienced patients (89.3%; 95% CI, 83.4%-95.3%). Virologic failure occurred in 34 patients (8%) overall. One patient died at posttreatment week 3; this was not considered related to study medication. There were 7 serious adverse events, all considered unrelated to study treatment, and 3 adverse events (&lt;1%) leading to treatment discontinuation, including 2 grade 4 alanine aminotransferase elevations. The most common adverse events (in ≥10% of patients) were headache, fatigue, diarrhea, and nausea. <h3>Conclusions and Relevance</h3> In this open-label, nonrandomized, uncontrolled study, a high rate of SVR12 was achieved in treatment-naive and treatment-experienced noncirrhotic patients with chronic HCV genotype 1 infection who received 12 weeks of treatment with the oral fixed-dose regimen of daclatasvir, asunaprevir, and beclabuvir. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01979939
Anson Jones: The Last President of Texas
Authors: F. Guerra
Journal: JAMA (1949)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
600. Fusion of HSV-1 Thymidine Kinase to an 11 aa-peptide from the HIV-1 Tat Protein Promotes Intercellular Trafficking and Enhances Anti-Tumoral Activity In Vivo
Authors: Ennio Tasciotti, Mauro Giacca
Journal: Molecular Therapy (2004)

Suicide gene therapy using herpes simplex virus type -1 (HSV-1) thymidine kinase (TK) is a widely exploited approach for gene therapy of cancer and other hyperproliferative disorders. Despite its popularity, clinical success has been so far hampered mostly by the relative inefficiency of TK gene transfer and its limited bystander effect.