tbuckley/cabot-search huggingface dataset:
Abstract A41: Role of UHRF1 in tumorigenesis and metastasis of osteosarcoma
Authors: Stephanie C. Wu, Claudia A. Benavente
Journal: Cancer Research (2018)

Abstract Osteosarcoma is the eighth most common form of childhood cancer, with very limited advances in treatment over the past three decades. Osteosarcoma is a highly metastatic cancer, with 15-20% of osteosarcoma patients diagnosed after the cancer has already metastasized, causing the survival rate to be little over 50%. Common sites of metastasis include lung and liver. Loss of the retinoblastoma protein (RB) is associated with poor prognosis in osteosarcoma, as defined by shorter life span and heavier tumor burden. Ubiquitin Like with PHD and Ring Finger Domains 1 (UHRF1) has been identified as a critical downstream effector of the RB/E2F pathway that is overexpressed in various cancers. We have confirmed using human mesenchymal stem cells (MSCs) and osteosarcoma cell lines that UHRF1 is directly regulated by the RB/E2F pathway in the bone lineage, and found that the UHRF1 gene is upregulated and its protein overexpressed in osteosarcoma. Using gain/loss-of-function assays to study the role of UHRF1 in osteosarcoma, we observed that UHRF1 is involved in promoting cell migration. To study the role of UHRF1 in osteosarcoma tumor development, we generated Uhrf1 conditional knockout mice. In this system, we use an Osterix-driven Cre recombinase (Osx-cre) to facilitate preosteoblast-specific loss of various combinations of genes. Osx-cre Tp53; Rb1 double knockout mice give rise to osteosarcoma and have a median survival of 26.7 weeks. Additional loss of Uhrf1 in Osx-cre Tp53; Rb1 double knockout mice (Osx-cre Tp53; Rb1; Uhrf1 triple knockout mice) significantly delays the age of tumor onset to &amp;gt;47 weeks. Furthermore, triple knockout mice have a decreased frequency and number of lung and liver metastasis. In conclusion, we have strong evidences both in vitro and in vivo that UHRF1 is a crucial component in aiding osteosarcoma progression, and have identified its novel role in tumor metastasis. The high metastatic rate and low 5-year survival rate following metastasis of osteosarcoma make UHRF1 a promising target for therapeutics. Further studies on the mechanism by which UHRF1 overexpression contributes to osteosarcomagenesis, including tumor growth and dissemination, will strongly aid the process of drug development for anticancer treatment. Citation Format: Stephanie C. Wu, Claudia A. Benavente. Role of UHRF1 in tumorigenesis and metastasis of osteosarcoma [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr A41.
Annals Graphic Medicine - The Tale of a Wannabe Superhero
Authors: Michelle Sayad
Journal: Annals of Internal Medicine (2019)

Web Exclusives5 February 2019Annals Graphic Medicine - The Tale of a Wannabe SuperheroFREEMichelle Sayad, MDMichelle Sayad, MDBaltimore, Maryland (M.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G18-0011 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Baltimore, Maryland (M.S.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G18-0011.Corresponding Author: Michelle Sayad, MD; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAnnals Graphic Medicine - Team Doctor Shruti Sudhakar Annals Graphic Medicine - What It Is Like Gazi M. Rashid Reimagining the Cape: Exploring New Metaphors for Emerging Medical Professionals Michael J. Green Reimagining the Cape: Exploring New Metaphors for Emerging Medical Professionals Michael J. Green Annals Graphic Medicine - The Med Student Mollie Kotzen Metrics Cited byThe 7 Habits of Highly Effective Cost-of-Care ConversationsCaroline E. Sloan, MD and Peter A. Ubel, MDTools to Help Overcome Barriers to Cost-of-Care ConversationsC. Jessica Dine, MD, MSHP, Domitilla Masi, MS, and Cynthia D. Smith, MDReimagining the Cape: Exploring New Metaphors for Emerging Medical ProfessionalsMichael J. Green, MD, MS 5 February 2019Volume 170, Issue 3Page: W54-W62KeywordsConflicts of interestDisclosureHealth care ePublished: 5 February 2019 Issue Published: 5 February 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Bio‐adrenomedullin as a marker of congestion in patients with new‐onset and worsening heart failure
Authors: Jozine M. ter Maaten, Daan Kremer, Biniyam G. Demissei, Joachim Struck, Andreas Bergmann, Stefan D. Anker, Leong L. Ng, Kenneth Dickstein, Marco Metra, Nilesh J. Samani, Simon P.R. Romaine, John Cleland, Nicolas Girerd, Chim C. Lang, Dirk J. van Veldhuisen, Adriaan A. Voors
Journal: European Journal of Heart Failure (2019)
Neurologist must pay damages for not telling former colleague’s wife about drug side effects
Authors: Clare Dyer
Journal: BMJ (2019)

A consultant neurologist must pay damages to the wife of a former colleague he was treating privately without charge, after failing to fully discuss the side effects of medication she was taking, a High Court judge has ruled.1

Hazel Kennedy, then aged 44, developed an upper limb tremor in 2006. Jonathan Frankel diagnosed Parkinson’s disease and treated her from 2007 to 2013 at the request of her husband, Philip Kennedy, who had retired as a consultant neurologist in 2006. Frankel, unlike Kennedy, was a specialist in movement disorders.

Hazel Kennedy developed impulse control disorder, a side effect of the drug she was given, and eventually went on to develop psychosis. This led her to make serious unfounded allegations against her husband, to leave the family home, and to start divorce proceedings.

The damages will be decided by the court later …
Abstract 16253: Distinctive Functions of PI3Kβ in Endothelial Cells and Cardiomyocytes in Response to Myocardial Infarction: Complications for Targeting PI3Kβ in Myocardial Infarction Treatment
Authors: Xueyi Chen, Pavel Zhabyeyev, Jessica DesAulniers, Xiuhua Wang, Faqi Wang, Allan G Murray, Zamaneh Kassiri, Bart Vanhaesebroeck, Gavin Y Oudit
Journal: Circulation (2016)

Introduction: Differential cellular responses and signaling cascades contribute to cardiac remodeling after myocardial infarction (MI). The phosphoinositide 3-kinase (PI3K)/Akt pathway regulates multiple pathways in post-MI remodeling. Hypothesis: The PI3K isoform, p110β, in endothelial cells and cardiomyocytes mediates distinct responses to MI. Methods: Mice with kinase-dead p110β expressed specifically in cardiomyocytes (p110β-αMHC) or endothelial cells (p110β-Tie2) were generated; p110β-Flx was used as littermate controls. Intraperitoneal injection of Tamoxifen (2mg/mouse for 5 days) was given to 9-week-old p110β-Tie2 to activate kinase-dead p110β expression. Sham- or MI-operation on 12-week-old mice and 7-day post-operated echocardiography were performed in a blinded fashion. Triphenyl tetrazolium chloride (TTC), CD31, and wheat germ agglutinin (WGA) staining were performed to examine the infarct size, vascular density, and hypertrophy on 7-day post-operated mice. Signaling pathways were assessed by W...
Validation of the Khorana Score in Acute Myeloid Leukemia Patients: A Single Institution Experience
Authors: Sayeef Mirza, Seongseok Yun, Najla Al Ali, Maher Elharake, Nathan Visweshwar, Daniel Schwartz, Katherine Robinson, Ethan Nowell, Grace Engle, Ibraahim Badat, Thomas Brimer, Amra Kuc, Ashton Sequeira, Sabbir Mirza, Dhiraj Sikaria, Jesus Diaz Vera, Noah Hackney, Rami S. Komrokji, Michael Jaglal
Journal: Blood (2018)
Efficacy of Lanadelumab in Hereditary Angioedema Patients Switching From C1 Inhibitor Long-Term Prophylaxis: Interim Results From the HELP Open-Label Extension Study
Authors: Marc A. Riedl, John T. Anderson, Marco Cicardi, H. Henry Li, Richard F. Lockey, Hilary Longhurst, Marcus Maurer, Peng Lu, James Hao, Aleena Banerji
Journal: Journal of Allergy and Clinical Immunology (2019)
Association of Nonsteroidal Anti-inflammatory Drug Prescriptions With Kidney Disease Among Active Young and Middle-aged Adults
Authors: D. Alan Nelson, Eric S. Marks, Patricia A. Deuster, Francis G. O’Connor, Lianne M. Kurina
Journal: JAMA Network Open (2019)

IMPORTANCE Concern about the renal effects of nonsteroidand al anti-inflammatory drugs (NSAIDs) among young, healthy adults has been limited, but more attention may be warranted given the prevalent use of these agents. OBJECTIVETo test for associations between dispensed NSAIDs and incident acute kidney injury and chronic kidney disease while controlling for other risk factors.DESIGN, SETTING, AND PARTICIPANTS This retrospective, longitudinal cohort study used deidentified medical and administrative data on 764 228 active-duty US Army soldiers serving between January 1, 2011, and December 31, 2014.Analysis was conducted from August 1 to November 30, 2018.All individuals new to Army service were included in the analysis.Persons already serving in January 2011 were required to have at least 7 months of observable time to eliminate those with kidney disease histories.EXPOSURES Mean total defined daily doses of prescribed NSAIDs dispensed per month in the prior 6 months.MAIN OUTCOMES AND MEASURES Incident outcomes were defined by diagnoses documented in health records and a military-specific digital system.RESULTS Among the 764 228 participants (655 392 [85.8%] men; mean [SD] age, 28.6 [7.9] years; median age, 27.0 years [interquartile range, 22.0-33.0years]), 502 527 (65.8%) were not dispensedprescription NSAIDs in the prior 6 months, 137 108 (17.9%) were dispensed 1 to 7 mean total defined daily doses per month, and 124 594 (16.3%) received more than 7 defined daily doses per month.There were 2356 acute kidney injury outcomes (0.3% of participants) and 1634 chronic kidney disease outcomes (0.2%) observed.Compared with participants who received no medication, the highest exposure level was associated with significantly higher adjusted hazard ratios (aHRs) for acute kidney injury (aHR, 1.2; 95% CI, 1.1-1.4)and chronic kidney disease (aHR, 1.2; 95% CI, 1.0-1.3),with annual outcome excesses per 100 000 exposed individuals totaling 17.6 cases for acute kidney injury and 30.0 cases for chronic kidney disease. CONCLUSIONS AND RELEVANCEModest but statistically significant associations were noted between the highest observed doses of NSAID exposure and incident kidney problems among active young and middle-aged adults.
Abstract 17586: Effect of Myocardial Infiltration of Dendritic Cells, Macrophages and T Lymphocytes on Long-term Prognosis in Patients With Dilated Cardiomyopathy
Authors: Takafumi Nakayama, Yasuo Sugano, Masao Takigami, Tetsuo Yokokawa, Toshiyuki Nagai, Hideaki Kanzaki, Keiko O Ogo, Taka-aki Matsuyama, Yoshihiko Ikeda, Hatsue I Ueda, Takeshi Nakatani, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
Journal: Circulation (2014)

Background: Dilated cardiomyopathy (DCM) is considered to be multifactorial, and its disease progression is diverse in each patient clinically. Recent reports have provided suggestive pathological ...
Peripheral and Central Sensitization of Pain in Individuals With Hand Osteoarthritis and Associations With Self‐Reported Pain Severity
Authors: Pernille Steen Pettersen, Tuhina Neogi, Karin Magnusson, Hilde Berner Hammer, Till Uhlig, Tore K. Kvien, Ida K. Haugen
Journal: Arthritis & Rheumatology (2019)

Pain sensitization, an important osteoarthritis (OA) pain mechanism, has not been substantially investigated in patients with hand OA. It is unknown how peripheral and central sensitization are related to self-reported hand pain.
The Lysine Histone Methyltransferase SETD2 Is Required for Appropriate Immunoglobulin VDJ Recombination
Authors: S. Haihua Chu, Jonathan Chabon, Janna Minehart, Chloe N Matovina, Jian Zhang, Bo-Ruei Chen, Elsa Callen-Moreu, Putzer J Hung, Zhaohui Feng, Richard Koche, X. Shirley Liu, Jayanta Chaudhuri, Andre Nussenzweig, Barry Sleckman, Scott A. Armstrong
Journal: Blood (2018)
TP53 Mutations Predict Poorer Responses to CPX-351 in Acute Myeloid Leukemia
Authors: Aaron D Goldberg, Chetasi Talati, Pinkal Desai, Christopher Famulare, Sean M Devlin, Noushin Farnoud, David A Sallman, Jeffrey E. Lancet, Gail J. Roboz, Kendra L. Sweet, Martin S. Tallman
Journal: Blood (2018)
Management of Hypertension in Chronic Kidney Disease
Authors: Dan Pugh, Peter J. Gallacher, Neeraj Dhaun
Journal: Drugs (2019)

Abstract Chronic kidney disease (CKD) is an increasingly prevalent condition globally and is strongly associated with incident cardiovascular disease (CVD). Hypertension is both a cause and effect of CKD and affects the vast majority of CKD patients. Control of hypertension is important in those with CKD as it leads to slowing of disease progression as well as reduced CVD risk. Existing guidelines do not offer a consensus on optimal blood pressure (BP) targets. Therefore, an understanding of the evidence used to create these guidelines is vital when considering how best to manage individual patients. Non-pharmacological interventions are useful in reducing BP in CKD but are rarely sufficient to control BP adequately. Patients with CKD and hypertension will often require a combination of antihypertensive medications to achieve target BP. Certain pharmacological therapies provide additional BP-independent renoprotective and/or cardioprotective action and this must be considered when instituting therapy. Managing hypertension in the context of haemodialysis and following kidney transplantation presents further challenges. Novel therapies may enhance treatment in the near future. Importantly, a personalised and evidence-based management plan remains key to achieving BP targets, reducing CVD risk and slowing progression of CKD.
Drugging RB1 Deficiency: Synthetic Lethality with Aurora Kinases
Authors: Frederick A. Dick, Shawn Shun-Cheng Li
Journal: Cancer Discovery (2019)

Two recent reports describe pharmacologic approaches to specifically treat RB1-mutant cancers. The basis of this approach is a synthetic lethal relationship between RB1 mutations and inhibition of Aurora kinases A or B.See related article by Oser et al., p. 230.See related article by Gong et al., p. 248.
Medical cannabis: no NHS patients have benefited from law change, say campaigners
Authors: Richard Hurley
Journal: BMJ (2019)

Very few UK patients have gained access to previously illegal cannabis based medicinal products since doctors were given permission to prescribe them in November 2018, and patients are complaining.

“The situation is appalling. Not one patient has benefited from a cannabis prescription on the NHS,” Mike Barnes, honorary professor of neurological rehabilitation at Newcastle University, told The BMJ . “The legislation has had no impact on the health of people who remain criminalised due to the lack of education of the medical community and overcautious guidelines produced by the Royal College of Physicians and the British Paediatric Neurology Association.”

Links to the guidelines were given in a letter to doctors from the Department of Health and Social Care and NHS England in October last year.1

Campaigners say that the guidelines, together with doctors’ and NHS managers’ fear of and lack of training in prescribing cannabis products, are major barriers.

Since 1 November 2018 doctors have been able to legally prescribe unlicensed products containing tetrahydrocannabinol (box). But the British Paediatric Neurology Association’s guidelines recommend against prescribing any product containing this cannabinoid, rendering the law change meaningless if doctors follow the recommendation.

In an open letter the parents of 39 children with intractable epilepsy recently called for the association to …
Incidence rates of inflammatory bowel disease in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis treated with secukinumab: a retrospective analysis of pooled data from 21 clinical trials
Authors: Stefan Schreiber, Jean-Frederic Colombel, Brian G Feagan, Kristian Reich, Atul A Deodhar, Iain B McInnes, Brian Porter, Ayan Das Gupta, Luminita Pricop, Todd Fox
Journal: Annals of the Rheumatic Diseases (2019)

Objectives Here, we present the reported incidence rates of inflammatory bowel disease (IBD) in patients receiving treatment with secukinumab for psoriasis (PsO), psoriatic arthritis (PsA) or ankylosing spondylitis (AS), in a pooled analysis of 21 clinical trials. Methods Data from all patients who had received at least one dose of secukinumab were included. Safety analyses were conducted to evaluate cumulative IBD rates as well as per-year rates, by indication. Crohn’s disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU) events were analysed using exposure-adjusted incidence rates (patient incidence rates per 100 patient-years (PY)). Results A total of 7355 patients with a cumulative exposure of 16 226.9 PY were included in the pooled analysis. Among 5181 patients with PsO, there were 14 cases of UC, 5 cases of CD and 1 case of IBDU, with exposure adjusted incidence rates (EAIRs) of 0.13, 0.05 and 0.01, respectively. Of these 20 cases, 14 were new-onset. In 1380 patients with PsA, there were 3 cases of UC, 3 cases of CD and 2 cases of IBDU (EAIRs 0.08, 0.08 and 0.05); 7 of these represented new-onset cases. Among 794 patients with AS, there were 4 cases of UC, 8 cases of CD and 1 case of IBDU (EAIRs 0.2, 0.4 and 0.1); 9 were new-onset cases. In the per year analysis, the EAIRs for each indication did not increase over time with secukinumab treatment. Conclusions In this pooled secukinumab safety analysis of 7355 patients across 21 clinical trials, cases of IBD events (including CD, UC and IBDU) were uncommon.
Acculturation is associated with asthma burden and pulmonary function in Latino youth: The GALA II study
Authors: Neeta Thakur, Luisa N. Borrell, Morgan Ye, Sam S. Oh, Celeste Eng, Kelley Meade, Pedro C. Avila, Harold J. Farber, Denise Serebrisky, Emerita Brigino-Buenaventura, William Rodriguez-Cintron, Rajesh Kumar, Kirsten Bibbins-Domingo, Shannon Thyne, Saunak Sen, Jose R. Rodriguez-Santana, Esteban G. Burchard
Journal: Journal of Allergy and Clinical Immunology (2019)
Noninvasive temperature monitoring for dual-modal tumor therapy based on lanthanide-doped up-conversion nanocomposites
Authors: Xueke Sun, Jiao Sun, Biao Dong, Gaosheng Huang, Li Zhang, Wanhui Zhou, Jiekai Lv, Xinran Zhang, Min Liu, Lin Xu, Xue Bai, Wen Xu, Yudan Yang, Xiuling Song, Hongwei Song
Journal: Biomaterials (2019)
Development of Novel Micro-dystrophins with Enhanced Functionality
Authors: Julian N. Ramos, Katrin Hollinger, Niclas E. Bengtsson, James M. Allen, Stephen D. Hauschka, Jeffrey S. Chamberlain
Journal: Molecular Therapy (2019)

Gene therapies using adeno-associated viral (AAV) vectors have advanced into clinical trials for several diseases, including Duchenne muscular dystrophy (DMD). A limitation of AAV is the carrying capacity (∼5 kb) available for genes and regulatory cassettes (RCs). These size constraints are problematic for the 2.2-Mb dystrophin gene. We previously designed a variety of miniaturized micro-dystrophins (μDys) that displayed significant, albeit incomplete, function in striated muscles. To develop μDys proteins with improved performance, we explored structural modifications of the dystrophin central rod domain. Eight μDys variants were studied that carried unique combinations of between four and six of the 24 spectrin-like repeats present in the full-length protein, as well as various hinge domains. Expression of μDys was regulated by a strong but compact muscle-restricted RC (CK8e) or by the ubiquitously active cytomegalovirus (CMV) RC. Vectors were evaluated by intramuscular injection and systemic delivery to dystrophic mdx4cv mice, followed by analysis of skeletal muscle pathophysiology. Two μDys designs were identified that led to increased force generation compared with previous μDys while also localizing neuronal nitric oxide synthase to the sarcolemma. An AAV vector expressing the smaller of these (μDys5) from the CK8e RC is currently being evaluated in a DMD clinical trial.
Sex and Genotype in Long QT Syndrome Risk Stratification
Authors: Wojciech Zareba
Journal: JAMA Cardiology (2019)

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 Cardiology 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 Cardiology journal
Hepatic Encephalopathy: Definition, Clinical Grading and Diagnostic Principles
Authors: Karin Weissenborn
Journal: Drugs (2019)

In general, hepatic encephalopathy (HE) is defined as a brain dysfunction caused by liver insufficiency and/or portal-systemic blood shunting. This article relates to the so-called type C HE: that is, HE in patients with liver cirrhosis. It manifests as a wide spectrum of neurological or psychiatric abnormalities, ranging from subclinical alterations, detectable only by neuropsychological or neurophysiological assessment, to coma. Several scales have been developed for grading the extent of HE. The most often used is the West Haven criteria (WHC), which differentiate between four grades of clinically overt HE. Patients with liver cirrhosis without clinically overt symptoms of HE but neuropsychological or neurophysiological findings indicating brain dysfunction are considered to have minimal hepatic encephalopathy (MHE). For simplification, some experts suggest differentiating between covert HE (MHE plus grade I HE according to WHC) and overt HE (WHC grades II–IV). Diagnosis of both MHE and overt HE is hampered by the fact that none of the symptoms of HE or the findings in the various diagnostic measures applied are specific. Thus, a diagnosis of HE or MHE can only be made after exclusion of other possible causes of brain dysfunction.
Abstract 17028: Screening Collegiate Athletes: The Reliability of the Preparticipation Survey. The Dartmouth College Athletic Screening Registry
Authors: Timothy A Beaver, Christopher R Russo, Tracy A Purcell, David J Malenka
Journal: Circulation (2016)

Introduction: Screening for risk of sudden cardiac death in highly conditioned athletes is a requirement for all students prior to participation in an NCAA sanctioned sport. However, despite the Am...
Dynamic BH3 Profiling Predicts Patient Response and MRD Status in Chronic Lymphocytic Leukemia (CLL) Patients Undergoing Frontline Treatment with Kinase Inhibitor Plus FCR (KI+FCR)
Authors: Timothy Z. Lehmberg, Rebecca Valentin, Stacey M. Fernandes, Jennifer R. Brown, Matthew S Davids
Journal: Blood (2018)