tbuckley/cabot-search huggingface dataset:
TIAM1 Antagonizes TAZ/YAP Both in the Destruction Complex in the Cytoplasm and in the Nucleus to Inhibit Invasion of Intestinal Epithelial Cells
Authors: Zoi Diamantopoulou, Gavin White, Muhammad Z.H. Fadlullah, Marcel Dreger, Karen Pickering, Joe Maltas, Garry Ashton, Ruth MacLeod, George S. Baillie, Valerie Kouskoff, Georges Lacaud, Graeme I. Murray, Owen J. Sansom, Adam F.L. Hurlstone, Angeliki Malliri
Journal: Cancer Cell (2017)
Insulin-Induced Distant Site Lipoatrophy
Authors: Aki Kondo, Akinobu Nakamura, Jun Takeuchi, Hideaki Miyoshi, Tatsuya Atsumi
Journal: Diabetes Care (2017)

A 46-year-old Japanese woman with type 2 diabetes noticed a depression in her right anterior abdomen where she had previously injected insulin for approximately 9 months (human neutral protamine Hagedorn insulin and insulin lispro), and this lesion expanded to her right groin. About 18 months after the insulin injections were stopped, a second depression lesion appeared on her left buttock where she had never injected insulin (Fig. 1 A–C ). Computed tomography showed lipoatrophy of the right submandibular region, right anterior abdomen, and left buttock sites (Fig. 1 D and E ). Laboratory data showed high values of HbA1c (8.9% [73 mmol/mol]) and fasting insulin levels (1,163 µU/mL). The insulin antibody titer was over 5,000 nU/mL, and the binding rate was 86.7%. Insulinoma was negative, with no increase in her fasting C-peptide level, …
Clinical Studies of Sequential Dreams
Journal: JAMA (1963)

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
Peaches and cream in a multi-ethnic society
Authors: Pip Fisher
Journal: BMJ (2017)

We had worked systematically from general inspection to examination of the hands, taken the pulse, and now we were on the face. We were revising the signs of thyroid disease. 

“Peaches and cream complexion in hypothyroidism.” offered one of the students. 

The answer was correct according to the textbooks, but as I looked at the …
What is hot …
Authors: Elizabeth Batalla-Duran
Journal: Thorax (2017)

It is not unusual for high sensitivity cardiac troponin (cTnT) to be measured when a patient presents to hospital with chest symptoms. Often the result can be slightly raised despite the primary problem not being cardiac. It seems logical that a severe pneumonia may cause a troponin leak by causing strain on the heart. This study by Vestjens et al (http://dx.doi.org/10.1111/resp.12996) sought to see if elevated troponin is a prognostic marker in patients admitted with community-acquired pneumonia (CAP).The study looked at cTnT levels on admission in 295 patients admitted with CAP. Levels were elevated (>14 ng/L) in 45%. Short-term (30 days) and long-term (up to 4.1 years) mortality were significantly higher in those with elevated cTnT. Elevated cTNT >28 ng/L was found to be a strong independent risk factor for mortality both short-term (OR 21.9, 95% CI 4.7 to 101.4) and long-term (OR 10.7, 95% CI 5.0 to 22.8). The study also combined troponin levels with the Pneumonia Severity Index (PSI) and found this was a stronger predictor of short-term mortality than PSI score alone. …
A Phase I Study of ABC294640, a First-in-Class Sphingosine Kinase-2 Inhibitor, in Patients with Advanced Solid Tumors
Authors: Carolyn D. Britten, Elizabeth Garrett-Mayer, Steven H. Chin, Keisuke Shirai, Besim Ogretmen, Tricia A. Bentz, Alan Brisendine, Kate Anderton, Susan L. Cusack, Lynn W. Maines, Yan Zhuang, Charles D. Smith, Melanie B. Thomas
Journal: Clinical Cancer Research (2017)

Purpose: Sphingosine kinases (SK1 and SK2) regulate tumor growth by generating the mitogenic and proinflammatory lipid sphingosine 1-phosphate (S1P). This phase I study investigated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of ABC294640, a first-in-class orally available inhibitor of SK2.Experimental Design: Escalating doses of ABC294640 were administered orally to patients with advanced solid tumors in sequential cohorts at the following dose levels: 250 mg qd, 250 mg bid, 500 mg bid, and 750 mg bid, continuously in cycles of 28 days. Serial blood samples were obtained to measure ABC294640 concentrations and sphingolipid profiles.Results: Twenty-two patients were enrolled, and 21 received ABC294640. The most common drug-related toxicities were nausea, vomiting, and fatigue. Among the 4 patients at 750 mg bid, one had dose-limiting grade 3 nausea and vomiting, and 2 were unable to complete cycle 1 due to diverse drug-related toxicities. The 500 mg bid dose level was established as the recommended phase II dose. ABC294640 administration resulted in decreases in S1P levels over the first 12 hours, with return to baseline at 24 hours. The best response was a partial response in a patient with cholangiocarcinoma at 250 mg qd, and stable disease was observed in 6 patients with various solid tumors across dose levels.Conclusions: At 500 mg bid, ABC294640 is well tolerated and achieves biologically relevant plasma concentrations. Changes in plasma sphingolipid levels may provide a useful pharmacodynamic biomarker for ABC294640. Clin Cancer Res; 23(16); 4642-50. ©2017 AACR.
The emerging role of maxillofacial radiology in the diagnosis and management of patients with complex periodontitis
Authors: William C. Scarfe, Bruno Azevedo, Lucas R. Pinheiro, Menik Priaminiarti, Marcelo A. O. Sales
Journal: Periodontology 2000 (2017)

Abstract Contemporary periodontal therapy has evolved to become more interdisciplinary and increasingly involves more complex treatments, including bone and soft‐tissue regenerative procedures. Therapeutic options require an imaging modality or combination of techniques that are capable of providing a diagnostic osseous baseline and facilitating quantification of smaller increments of bony change, both loss and additive, which are comparable over time. Intra‐oral and panoramic radiography are the modalities most commonly used to identify the location, quantify the amount and the pattern of alveolar bone loss and determine response to therapy. Cone‐beam computed tomography imaging offers specific advantages for periodontal diagnosis in that three‐dimensional images of dental and alveolar bone structures can be rendered with accuracy. Cone‐beam computed tomography has been shown to be clinically efficacious in demonstrating localized defects, such as furcation involvement and intrabony vertical and buccal/lingual defects, and in assessing the effects of regenerative therapy. In these situations, limited‐field‐of‐view, high‐resolution protocols are indicated.
Direct Pharmacological Targeting of a Mitochondrial Ion Channel Selectively Kills Tumor Cells In Vivo
Authors: Luigi Leanza, Matteo Romio, Katrin Anne Becker, Michele Azzolini, Livio Trentin, Antonella Managò, Elisa Venturini, Angela Zaccagnino, Andrea Mattarei, Luca Carraretto, Andrea Urbani, Stephanie Kadow, Lucia Biasutto, Veronica Martini, Filippo Severin, Roberta Peruzzo, Valentina Trimarco, Jan-Hendrik Egberts, Charlotte Hauser, Andrea Visentin, Gianpietro Semenzato, Holger Kalthoff, Mario Zoratti, Erich Gulbins, Cristina Paradisi, Ildiko Szabo
Journal: Cancer Cell (2017)
No Advantages of Fractionated Versus Single Dose(s) of Gemtuzumab Ozogamicin (GO) As Part of the Midam Salvage Regimen in Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients
Authors: Pierre Peterlin, Thierry Guillaume, Jacques Delaunay, Mohamad Mohty, Alice Garnier, Fanny Rialland, Marion Strullu, Beatrice Mahe, Viviane Dubruille, Nicolas Blin, Maud Voldoire, Cyrille Touzeau, Thomas Gastinne, Steven Le Gouill, Philippe Moreau, Patrice Chevallier
Journal: Blood (2015)
Are More Young People Having Strokes?—A Simple Question With an Uncertain Answer
Authors: James F. Burke, Lesli E. Skolarus
Journal: JAMA Neurology (2017)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Neurology journal
When Good Intentions Are Not Enough
Authors: Jinan Usta
Journal: JAMA Pediatrics (2017)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal
Convergent Balancing Selection on the Mu-Opioid Receptor in Primates
Authors: Carolyn G. Sweeney, Juliette M. Rando, Helen N. Panas, Gregory M. Miller, Donna M. Platt, Eric J. Vallender
Journal: Molecular Biology and Evolution (2017)

The mu opioid receptor is involved in many natural processes including stress response, pleasure, and pain. Mutations in the gene also have been associated with opiate and alcohol addictions as well as with responsivity to medication targeting these disorders. Two common and mutually exclusive polymorphisms have been identified in humans, A118G (N40D), found commonly in non-African populations, and C17T (V6A), found almost exclusively in African populations. Although A118G has been studied extensively for associations and in functional assays, C17T is much less well understood. In addition to a parallel polymorphism previously identified in rhesus macaques (Macaca mulatta), C77G (P26R), resequencing in additional non-human primate species identifies further common variation: C140T (P47L) in cynomolgus macaques (Macaca fascicularis), G55C (D19H) in vervet monkeys (Chlorocebus aethiops sabeus), A111T (L37F) in marmosets (Callithrix jacchus), and C55T (P19S) in squirrel monkeys (Saimiri boliviensis peruviensis). Functional effects on downstream signaling are observed for each of these variants following treatment with the endogenous agonist β-endorphin and the exogenous agonists morphine, DAMGO ([d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin), and fentanyl. In addition to demonstrating the importance of functional equivalency in reference to population variation for minority health, this also shows how common evolutionary pressures have produced similar phenotypes across species, suggesting a shared response to environmental needs and perhaps elucidating the mechanism by which these organism-environment interactions are mediated physiologically and molecularly. These studies set the stage for future investigations of shared functional polymorphisms across species as a new genetic tool for translational research.
Erratum: Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy
Authors: Frank H Yu, Massimo Mantegazza, Ruth E Westenbroek, Carol A Robbins, Franck Kalume, Kimberly A Burton, William J Spain, G Stanley McKnight, Todd Scheuer, William A Catterall
Journal: Nature Neuroscience (2006)
Abstract 316: Enhanced Cardiac Proteasome Function in the Naked Mole-rat, the Longest-lived Rodent
Authors: David A Kramer, Kelly M Grimes, Rochelle Buffenstein
Journal: Circulation Research (2015)

The ubiquitin-proteasome system (UPS) is responsible for the recycling of misfolded proteins. Dysfunction of the UPS has been implicated in the pathophysiology of multiple heart disorders, including heart failure and reperfusion injury, but the basic science of cardiac UPS function remains unclear. An attractive mode of inquiry into the cardiac proteasome is the long-lived naked mole rat (NMR), which maintains intact cardiac reserve and diastolic function exceptionally late into its lifespan; equivalent to a 90 year old human with a 30 year old’s heart. In this study, we investigated whether the long-lived and healthful NMR had upregulated aspects of UPS function in comparison to the short-lived well-characterized mouse. NMR hearts have more than twofold (p&lt;0.001) greater proteasome-mediated chymotrypsin-like activity than mouse hearts. NMR hearts also have significantly greater levels of proteasome subunits than mice, including α7 and Rpt5, suggesting that the greater numbers of proteasomes could contribute to the high chymotrypsin-like activity, alternatively, the naked mole-rat heart may also have more immunoproteasomes which are more efficient. The UPS is energy-dependent, with its activity significantly influenced by available ATP. Interestingly, basal ATP levels were 40 to 50 fold higher in NMR hearts than in those of mice. This is consistent with the much larger pools of mitochondria observed in the NMR heart than in the mouse heart. Considering that both high and low ATP levels are associated with a decline in proteasome activity, we next asked whether the remarkably high basal ATP levels of the NMR heart caused a qualitative difference in UPS function between NMRs and mice. Levels of ubiquitinated protein were significantly lower in the NMR heart than in the mouse heart, suggesting that the NMR cardiac UPS system is more effective at destroying ubiquitin-tagged damaged proteins than that of the mouse, and that the NMR heart’s elevated ATP levels may play a physiological role in maintaining this enhanced UPS functionality. Overall these data suggest a high basal level of proteasome activity in the NMR heart that may be of paramount importance in this animal’s ability to withstand and/or prevent age-related cardiovascular functional declines.
ACCF/AHA 2007 Clinical Competence Statement on Vascular Imaging With Computed Tomography and Magnetic Resonance
Authors: Christopher M Kramer, Matthew J Budoff, Zahi A Fayad, Victor A Ferrari, Corey Goldman, John R Lesser, Edward T Martin, Sanjay Rajogopalan, John P Reilly, George P Rodgers, Lawrence Wechsler, Mark A Creager, David R Holmes, Geno Merli, L Kristin Newby, Ileana Piña, Howard H Weitz
Journal: Circulation (2007)
Rapid and Parallel Adaptive Evolution of the Visual System of Neotropical Midas Cichlid Fishes
Authors: Julián Torres-Dowdall, Michele E.R. Pierotti, Andreas Härer, Nidal Karagic, Joost M. Woltering, Frederico Henning, Kathryn R. Elmer, Axel Meyer
Journal: Molecular Biology and Evolution (2017)

Midas cichlid fish are a Central American species flock containing 13 described species that has been dated to only a few thousand years old, a historical timescale infrequently associated with speciation. Their radiation involved the colonization of several clear water crater lakes from two turbid great lakes. Therefore, Midas cichlids have been subjected to widely varying photic conditions during their radiation. Being a primary signal relay for information from the environment to the organism, the visual system is under continuing selective pressure and a prime organ system for accumulating adaptive changes during speciation, particularly in the case of dramatic shifts in photic conditions. Here, we characterize the full visual system of Midas cichlids at organismal and genetic levels, to determine what types of adaptive changes evolved within the short time span of their radiation. We show that Midas cichlids have a diverse visual system with unexpectedly high intra- and interspecific variation in color vision sensitivity and lens transmittance. Midas cichlid populations in the clear crater lakes have convergently evolved visual sensitivities shifted toward shorter wavelengths compared with the ancestral populations from the turbid great lakes. This divergence in sensitivity is driven by changes in chromophore usage, differential opsin expression, opsin coexpression, and to a lesser degree by opsin coding sequence variation. The visual system of Midas cichlids has the evolutionary capacity to rapidly integrate multiple adaptations to changing light environments. Our data may indicate that, in early stages of divergence, changes in opsin regulation could precede changes in opsin coding sequence evolution.
Thymosin α1 represents a potential potent single-molecule-based therapy for cystic fibrosis
Authors: Luigina Romani, Vasilis Oikonomou, Silvia Moretti, Rossana G Iannitti, Maria Cristina D'Adamo, Valeria R Villella, Marilena Pariano, Luigi Sforna, Monica Borghi, Marina M Bellet, Francesca Fallarino, Maria Teresa Pallotta, Giuseppe Servillo, Eleonora Ferrari, Paolo Puccetti, Guido Kroemer, Mauro Pessia, Luigi Maiuri, Allan L Goldstein, Enrico Garaci
Journal: Nature Medicine (2017)
Molecular Heterogeneity of the FIP1L1-PDGFRA Fusion Gene in Chronic Eosinophilic Leukemia (CEL) and Systemic Mastocytosis with Eosinophilia (SME): A Study of 43 Cases.
Authors: Christoph Walz, Daniela Cilloni, Simona Soverini, Catherine Roche, Emanuela Ottaviani, Giovanni Martinelli, Giuseppe Saglio, Claude Preudhomme, Peter Paschka, Jane Apperley, Andreas Hochhaus, Rüdiger Hehlmann, Nicholas C.P. Cross, David Grimwade, Andreas Reiter
Journal: Blood (2004)
Detection of interferon alpha protein reveals differential levels and cellular sources in disease
Authors: Mathieu P. Rodero, Jérémie Decalf, Vincent Bondet, David Hunt, Gillian I. Rice, Scott Werneke, Sarah L. McGlasson, Marie-Alexandra Alyanakian, Brigitte Bader-Meunier, Christine Barnerias, Nathalia Bellon, Alexandre Belot, Christine Bodemer, Tracy A. Briggs, Isabelle Desguerre, Marie-Louise Frémond, Marie Hully, Arn M.J.M. van den Maagdenberg, Isabelle Melki, Isabelle Meyts, Lucile Musset, Nadine Pelzer, Pierre Quartier, Gisela M. Terwindt, Joanna Wardlaw, Stewart Wiseman, Frédéric Rieux-Laucat, Yoann Rose, Bénédicte Neven, Christina Hertel, Adrian Hayday, Matthew L. Albert, Flore Rozenberg, Yanick J. Crow, Darragh Duffy
Journal: The Journal of Experimental Medicine (2017)

Type I interferons (IFNs) are essential mediators of antiviral responses. These cytokines have been implicated in the pathogenesis of autoimmunity, most notably systemic lupus erythematosus (SLE), diabetes mellitus, and dermatomyositis, as well as monogenic type I interferonopathies. Despite a fundamental role in health and disease, the direct quantification of type I IFNs has been challenging. Using single-molecule array (Simoa) digital ELISA technology, we recorded attomolar concentrations of IFNα in healthy donors, viral infection, and complex and monogenic interferonopathies. IFNα protein correlated well with functional activity and IFN-stimulated gene expression. High circulating IFNα levels were associated with increased clinical severity in SLE patients, and a study of the cellular source of IFNα protein indicated disease-specific mechanisms. Measurement of IFNα attomolar concentrations by digital ELISA will enhance our understanding of IFN biology and potentially improve the diagnosis and stratification of pathologies associated with IFN dysregulation.
867 Chemokines protect against paracetamol hepatotoxicity in model systems
Authors: C MAREK, J FREW, K SIMPSON, M WRIGHT
Journal: Hepatology (2003)

Cholangiocytes (ie, the epithelial cells that line the bile ducts) are an important subset of liver cells. They are actively involved in the modification of bile volume and composition, are activated by interactions with endogenous and exogenous stimuli (eg, microorganisms, drugs), and participate in liver injury and repair. The term cholangiopathies refers to a category of chronic liver diseases that share a central target: the cholangiocyte. The cholangiopathies account for substantial morbidity and mortality given their progressive nature, the challenges associated with clinical management, and the lack of effective medical therapies. Thus, cholangiopathies usually result in end-stage liver disease requiring liver transplant to extend survival. Approximately 16% of all liver transplants performed in the United States between 1988 and 2014 were for cholangiopathies. For all these reasons, cholangiopathies are an economic burden on patients, their families, and society. This review offers a concise summary of the biology of cholangiocytes and describes a conceptual framework for development of the cholangiopathies. We also present the recent progress made in understanding the pathogenesis of and how this knowledge has influenced therapies for the 6 common cholangiopathies—primary biliary cirrhosis, primary sclerosing cholangitis, cystic fibrosis involving the liver, biliary atresia, polycystic liver disease, and cholangiocarcinoma—because the latest scientific progress in the field concerns these conditions. We performed a search of the literature in PubMed for published papers using the following terms: cholangiocytes, biliary epithelia, cholestasis, cholangiopathy, and biliary disease. Studies had to be published in the past 5 years (from June 1, 2009, through May 31, 2014), and non-English studies were excluded.