tbuckley/cabot-search huggingface dataset:
Differential Expression of Alpha3Beta1 and Alpha6Beta4 Integrin Molecules on Different Rat and Human Esophageal Cell Lines
Authors: Roudabeh J. Jamasbi, Arup R. Chakraborty, Brian F. Schmidt, Steven J. Kennel
Journal: Cancer Research (2006)

2226  Integrins are heterodimeric transmembrane glycoproteins comprised of α and β subunits. These adhesive receptors interact with extracellular matrix proteins and influence the cell survival and proliferation processes. The main objective of this study was to determine the differential expression of α3β1 and α6β4 integrin molecules on rat tumorigenic esophageal cell lines (RE-B2T) and nontumorigenic transformed cell lines (RE-79, RE-149 and RE- 282). Rat kidney, trachea and fibroblast cells served as controls. In addition, the expression of these molecules on human esophageal cancer cell lines, established from well-to-poorly differentiated human cancers, was investigated. The expression of these integrin molecules was determined at the protein antigen level by ELISA and Western blot using monoclonal antibodies; and at the mRNA level by RT-PCR. The expression of these integrin molecules was higher on non-tumorigenic transformed cell lines, than on the tumorigenic one on the rat cell lines. The expression of β1 integrin also appeared to be higher on nontumorigenic rat cell lines at mRNA level. Although differential expression of these integrin molecules on human lines was observed, correlation between the degree of differentiation and the integrin expression was not established. It appears that the expression of these two molecules is down-regulated in invasive cancer cells, which may contribute to the metastatic capability of these cancers in vivo.
FibroScan Identifies Patients With Nonalcoholic Fatty Liver Disease and Cardiovascular Damage
Authors: Rosa Lombardi, Salvatore Petta, Giuseppina Pisano, Paola Dongiovanni, Luca Rinaldi, Luigi Elio Adinolfi, Carlo Acierno, Luca Valenti, Roberta Boemi, Federica Spatola, Antonio Craxì, Silvia Fargion, Anna Ludovica Fracanzani
Journal: Clinical Gastroenterology and Hepatology (2018)
Time Interval to Biochemical Failure as a Surrogate End Point in Locally Advanced Prostate Cancer: Analysis of Randomized Trial NRG/RTOG 9202
Authors: James J. Dignam, Daniel A. Hamstra, Herbert Lepor, David Grignon, Harmar Brereton, Adam Currey, Seth Rosenthal, Kenneth L. Zeitzer, Varagur M. Venkatesan, Eric M. Horwitz, Thomas M. Pisansky, Howard M. Sandler
Journal: Journal of Clinical Oncology (2018)

In prostate cancer, end points that reliably portend prognosis and treatment benefit (surrogate end points) can accelerate therapy development. Although surrogate end point candidates have been evaluated in the context of radiotherapy and short-term androgen deprivation (AD), potential surrogates under long-term (24 month) AD, a proven therapy in high-risk localized disease, have not been investigated.In the NRG/RTOG 9202 randomized trial (N = 1,520) of short-term AD (4 months) versus long-term AD (LTAD; 28 months), the time interval free of biochemical failure (IBF) was evaluated in relation to clinical end points of prostate cancer-specific survival (PCSS) and overall survival (OS). Survival modeling and landmark analysis methods were applied to evaluate LTAD benefit on IBF and clinical end points, association between IBF and clinical end points, and the mediating effect of IBF on LTAD clinical end point benefits.LTAD was superior to short-term AD for both biochemical failure (BF) and the clinical end points. Men remaining free of BF for 3 years had relative risk reductions of 39% for OS and 73% for PCSS. Accounting for 3-year IBF status reduced the LTAD OS benefit from 12% (hazard ratio [HR], 0.88; 95% CI, 0.79 to 0.98) to 6% (HR, 0.94; 95% CI, 0.83 to 1.07). For PCSS, the LTAD benefit was reduced from 30% (HR, 0.70; 95% CI, 0.52 to 0.82) to 6% (HR, 0.94; 95% CI, 0.72 to 1.22). Among men with BF, by 3 years, 50% of subsequent deaths were attributed to prostate cancer, compared with 19% among men free of BF through 3 years.The IBF satisfied surrogacy criteria and identified the benefit of LTAD on disease-specific survival and OS. The IBF may serve as a valid end point in clinical trials and may also aid in risk monitoring after initial treatment.
A First in COPD Treatment
Authors: Rebecca Voelker
Journal: JAMA (2018)

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
Donald Irvine: the only GP to date to become president of the General Medical Council
Authors: Rebecca Wallersteiner
Journal: BMJ (2018)

Nick Sinclair’s 1996 portrait of Donald Irvine was given by The BMJ to the National Portrait Gallery

Credit: Nick Sinclair

Born in 1935 in Ashington, Northumberland, in a coal mining community where his father was a family doctor, the studious young Donald Irvine was educated at King Edward VI Grammar School in Morpeth. His father’s surgery was part of the house, and medicine was discussed every day. He recalled in his memoir, Medical Professionalism and the Public Interest ,1 that, “In those days there was a common assumption in medical families that son would follow father.” From childhood he helped unpack drugs that were delivered to the house in large glass containers. He and his sister, who also became a doctor, would often visit patients with their father.

Irvine remembered travelling to and from primary school in the early 1940s with miners on the bus still covered in coal dust. There were no supermarkets, no laundries, few telephones, no television, nor many of the things we take for granted today. At the age of 10, Irvine developed rheumatic fever and spent nearly a year in hospital. He always remembered the excellent care he received from …
Genetic association of non-MHC region with ankylosing spondylitis in a Chinese population
Authors: Jing Liu, Weilin Pu, Yuan Li, Yanyun Ma, Qi Zhu, Wei Wan, Chengde Yang, Xiaofeng Wang, Xingdong Chen, Xiaodong Zhou, John D Reveille, Li Jin, Hejian Zou, Jiucun Wang
Journal: Annals of the Rheumatic Diseases (2018)

Ankylosing spondylitis (AS) is a chronic inflammatory disease mainly affecting the sacroiliac joints and spine.1 In order to examine overall genetic susceptibility of AS, several genome-wide association studies (GWASs) were performed in Caucasian populations, and a number of genetic polymorphisms in non-major histocompatibility complex (MHC) regions were found, such as ERAP1 , IL23R as well as many others.2–6 However, only a small portion of the single nucleotide polymorphisms (SNPs) were validated in East Asian (EA) populations.2 In recent years, multiple studies indicated significant genetic differences between different European and EA populations.2 7 To resolve this further, we have examined all reported AS-associated SNPs in non-MHC regions in Chinese patients with AS. A total of 1289 patients with AS and 1536 controls were included in this analysis, which have not been included in prior analyses.2 7 The sociodemographic and clinical characteristics of the cohort are presented in online supplementary table S1.### Supplementary data

[annrheumdis-2018-214625supp001.docx] 

In this study, the candidate SNPs were mainly selected from six GWAS studies published from 2007 to 2016.2–6 8 Overall, 69 …
Childhood Body Composition Trajectories and Adolescent Lung Function. Findings from the ALSPAC study
Authors: Gabriela P. Peralta, Elaine Fuertes, Raquel Granell, Osama Mahmoud, Célina Roda, Ignasi Serra, Deborah Jarvis, John Henderson, Judith Garcia-Aymerich
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Body composition changes throughout life may explain the inconsistent associations reported between body mass index and lung function in children.
Self-Luminescing Theranostic Nanoreactors with Intraparticle Relayed Energy Transfer for Tumor Microenvironment Activated Imaging and Photodynamic Therapy
Authors: Ming Wu, Lingjie Wu, Jiong Li, Da Zhang, Shanyou Lan, Xiaolong Zhang, Xinyi Lin, Gang Liu, Xiaolong Liu, Jingfeng Liu
Journal: Theranostics (2018)

The low tissue penetration depth of external excitation light severely hinders the sensitivity of fluorescence imaging (FL) and the efficacy of photodynamic therapy (PDT) in vivo; thus, rational theranostic platforms that overcome the light penetration depth limit are urgently needed. To overcome this crucial problem, we designed a self-luminescing nanosystem (denoted POCL) with near-infrared (NIR) light emission and singlet oxygen (1O2) generation abilities utilizing an intraparticle relayed resonance energy transfer strategy. Methods: Bis[3,4,6-trichloro-2-(pentyloxycarbonyl) phenyl] oxalate (CPPO) as a chemical energy source with high reactivity toward H2O2, poly[(9,9'-dioctyl-2,7-divinylene-fluorenylene)-alt-2-methoxy- 5-(2-ethyl-hexyloxy)-1,4-phenylene] (PFPV) as a highly efficient chemiluminescence converter, and tetraphenylporphyrin (TPP) as a photosensitizer with NIR emission and 1O2 generation abilities were coencapsulated by self-assembly with poly(ethyleneglycol)-co-poly(caprolactone) (PEG-PCL) and folate-PEG-cholesterol to form the POCL nanoreactor, with folate as the targeting group. A series of in vitro and in vivo analyses, including physical and chemical characterizations, tumor targeting ability, tumor microenvironment activated imaging and photodynamic therapy, as well as biosafety, were systematically investigated to characterize the POCL. Results: The POCL displayed excellent NIR luminescence and 1O2 generation abilities in response to H2O2. Therefore, it could serve as a specific H2O2 probe to identify tumors through chemiluminescence imaging and as a chemiluminescence-driven PDT agent for inducing tumor cell apoptosis to inhibit tumor growth due to the abnormal overproduction of H2O2 in the tumor microenvironment. Moreover, the folate ligand on the POCL surface can further improve the accumulation at the tumor site via a receptor-mediated mechanism, thus enhancing tumor imaging and the therapeutic effects both in vitro and in vivo but without any observable systemic toxicity. Conclusion: The nanosystem reported here might serve as a targeted, smart, precise, and noninvasive strategy triggered by the tumor microenvironment rather than by an outside light source for cancer NIR imaging and PDT treatment without limitations on penetration depth.
Validation of Diagnostic and Performance Characteristics of the Wireless Motility Capsule in Patients With Suspected Gastroparesis
Authors: Allen A. Lee, Satish Rao, Linda A. Nguyen, Baharak Moshiree, Irene Sarosiek, Michael I. Schulman, John M. Wo, Henry P. Parkman, Gregory E. Wilding, Richard W. McCallum, William L. Hasler, Braden Kuo
Journal: Clinical Gastroenterology and Hepatology (2018)
Abstract 2679: Recombinant Human Interleukin-1 Receptor Antagonist- Anakinra Attenuates The Deterioration Of Motor Function Induced By Spinal Cord Ischemia In Rabbits
Authors: Satoshi Akuzawa, Teruhisa kazui, Enyi Shi, Katsushi Yamashita, Abul H Bashar, Hitoshi Terada, Naoki Washiyama, Takayasu Suzuki, Kazuhiro Ohkura
Journal: Circulation (2007)

Objective: In certain patients, thoracic and thoracoabdominal aortic surgery is complicated by subacute or delayed paraplegia. Pro-inflammatory cytokine interleukin-1β(IL-1β) has been implicated in...
Absence of Cardiomyocyte Differentiation Following Transplantation of Adult Cardiac-Resident Sca-1 <sup>+</sup> Cells Into Infarcted Mouse Hearts
Authors: Mark H. Soonpaa, Pascal J. Lafontant, Sean Reuter, John A. Scherschel, Edward F. Srour, Marc-Michael Zaruba, Michael Rubart-von der Lohe, Loren J. Field
Journal: Circulation (2018)

Although several lines of evidence suggest that the glycosyl phosphatidylinositol-anchored cell surface protein Sca-1 marks cardiac-resident stem cells, a critical analysis of the literature raises some concerns regarding their cardiomyogenic potential. 1Here, isolated adult cardiac-resident Sca-1 + cells were engrafted into infarcted hearts and monitored for cardiomyogenic differentiation.Donor cells were prepared from ACT-EGFP; MHC-nLAC double-transgenic mice ([C57/Bl6J x DBA/2J] F1 genetic background; all procedures followed were in accordance with Institutional Guidelines).The ACT-EGFP transgene targets ubiquitous expression of an enhanced green fluorescent protein reporter, and the MHC-nLAC transgene targets cardiomyocyte-restricted expression of a nuclear-localized βgalactosidase reporter.Donor cell survival was monitored via EGFP fluorescence, while cardiomyogenic differentiation was monitored by reacting with the chromogenic βgalactosidase substrate 5-bromo-4-chloro-3-indolyl-β-D-galactoside (X-GAL), which gives rise to a blue product. 2 Double-transgenic hearts were dispersed with Blendzyme and the resulting cells reacted with an APC-conjugated anti-Sca-1 antibody and a PE-conjugated cocktail of antibodies recognizing hematopoietic lineage markers. 3Sca-1 + , EGFP + , lineage - cells were then isolated via fluorescence-activated cell sorting (FACS; characterization of the donor cells is provided in Figure 1A), and 100,000 cells were injected into the infarct border zone of non-transgenic [C57/Bl6J x DBA/2J] F1 mice immediately following permanent coronary artery occlusion.
Abstract 17178: The Influence of Fontan-associated Protein-losing Enteropathy on Outcomes in Patients Referred for Heart Transplant: a Multicenter Study
Authors: Kurt R Schumacher, Sunkyung Yu, Ray Lowery, Ryan J Butts, Chesney Castleberry, Sharon Chen, Erik Edens, Justin Godown, Jonathan N Johnson, Mariska Kemna, Kimberly Y Lin, Kathleen Simpson, Shawn West, Ivan Wilmot, Jeffrey G Gossett
Journal: Circulation (2016)

Introduction: Fontan-associated protein-losing enteropathy (PLE) is an indication for heart transplant (HTx). Timing of referral varies widely, and the influence of PLE’s severity, duration, and tr...
Molecular Epidemiologic Associations in Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) within the United States
Authors: Adam Zrinski Albitar, Neil Shah, James K McCloskey, Jamie L. Koprivnikar, Jianhua Zhao, Chirag Desai, Sucha Sudarsanam, Maher Albitar, Catherine E. Lai
Journal: Blood (2018)
CG'806, a First-in-Class Pan-FLT3/Pan-BTK Inhibitor, Exhibits Broader and Greater Potency Than Ibrutinib Against Primary and Cultured Malignant B Cells
Authors: Hongying Zhang, Andrea Local, Khalid Benbatoul, Peter Folger, Susan Sheng, Taryn McLaughlin, Alexey V Danilov, Stephen E Kurtz, Jeffrey W. Tyner, Stephen Howell, William G Rice
Journal: Blood (2018)
Advancements in Life Cycle Human Exposure and Toxicity Characterization
Authors: Peter Fantke, Lesa Aylward, Jane Bare, Weihsueh A. Chiu, Robin Dodson, Robert Dwyer, Alexi Ernstoff, Brett Howard, Matti Jantunen, Olivier Jolliet, Richard Judson, Nienke Kirchhübel, Dingsheng Li, Aubrey Miller, Greg Paoli, Paul Price, Lorenz Rhomberg, Beverly Shen, Hyeong-Moo Shin, Justin Teeguarden, Daniel Vallero, John Wambaugh, Barbara A. Wetmore, Rosemary Zaleski, Thomas E. McKone
Journal: Environmental Health Perspectives (2018)

The Life Cycle Initiative, hosted at the United Nations Environment Programme, selected human toxicity impacts from exposure to chemical substances as an impact category that requires global guidance to overcome current assessment challenges. The initiative leadership established the Human Toxicity Task Force to develop guidance on assessing human exposure and toxicity impacts. Based on input gathered at three workshops addressing the main current scientific challenges and questions, the task force built a roadmap for advancing human toxicity characterization, primarily for use in life cycle impact assessment (LCIA).The present paper aims at reporting on the outcomes of the task force workshops along with interpretation of how these outcomes will impact the practice and reliability of toxicity characterization. The task force thereby focuses on two major issues that emerged from the workshops, namely considering near-field exposures and improving dose–response modeling.The task force recommended approaches to improve the assessment of human exposure, including capturing missing exposure settings and human receptor pathways by coupling additional fate and exposure processes in consumer and occupational environments (near field) with existing processes in outdoor environments (far field). To quantify overall aggregate exposure, the task force suggested that environments be coupled using a consistent set of quantified chemical mass fractions transferred among environmental compartments. With respect to dose–response, the task force was concerned about the way LCIA currently characterizes human toxicity effects, and discussed several potential solutions. A specific concern is the use of a (linear) dose–response extrapolation to zero. Another concern addresses the challenge of identifying a metric for human toxicity impacts that is aligned with the spatiotemporal resolution of present LCIA methodology, yet is adequate to indicate health impact potential.Further research efforts are required based on our proposed set of recommendations for improving the characterization of human exposure and toxicity impacts in LCIA and other comparative assessment frameworks. https://doi.org/10.1289/EHP3871.
Modulation of Insulin Resistance in Nonalcoholic Fatty Liver Disease
Authors: Reenam S. Khan, Fernando Bril, Kenneth Cusi, Philip N. Newsome
Journal: Hepatology (2018)

Nonalcoholic fatty liver disease (NAFLD) has an estimated prevalence of 25% in the general population, and cirrhosis secondary to nonalcoholic steatohepatitis (NASH) is predicted to become the leading cause of liver transplantation, yet there is a lack of effective licensed treatments for these conditions. There is a close relationship between insulin resistance (IR) and NAFLD, with prevalence of NAFLD being 5-fold higher in patients with diabetes compared to those without. IR is implicated both in pathogenesis of NAFLD and in disease progression from steatosis to NASH. Thus, modulation of IR represents a potential strategy for NAFLD treatment. This review highlights key proposed mechanisms linking IR and NAFLD, such as changes in rates of adipose tissue lipolysis and de novo lipogenesis, impaired mitochondrial fatty acid β-oxidation (FAO), changes in fat distribution, alterations in the gut microbiome, and alterations in levels of adipokines and cytokines. Furthermore, this review will discuss the main pharmacological strategies used to treat IR in patients with NAFLD and their efficacy based on recently published experimental and clinical data. These include biguanides, glucagon-like peptide 1 receptor (GLP-1) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors, peroxisome proliferator-activated receptor (PPAR-γ/α/δ) agonists, sodium glucose cotransporter 2 (SGLT2) inhibitors, and farnesoid X receptor (FXR) agonists, with further novel treatments on the horizon. Ideally, treatment would improve IR, reduce cardiovascular risk, and produce demonstrable improvements in NASH histology-this is likely to be achieved with a combinatorial approach.
Dancing Dorsal Quadrilaterals
Authors: Karlo J. Lizarraga, Philip D. Thompson, Henry P. Moore, Gabriel Mizraji, Oscar S. Gershanik, Carlos Singer, Anthony E. Lang
Journal: JAMA Neurology (2018)

Recognized peripherally induced movement disorders include the painful legs moving toes syndrome, postamputation dyskinesias, and belly dancer dyskinesias.To introduce and characterize the dancing dorsal quadrilaterals, a novel peripherally induced movement disorder that predominantly affects dorsal quadrilateral muscles (trapezius and rhomboids) after upper spine instrumentation.Between 1990 and 2015, a total of 4 patients who developed abnormal movements of the dorsal quadrilateral muscles after upper spine instrumentation were referred to movement disorders clinics at 3 academic medical centers in the United States, Canada, and Argentina. A prospective and retrospective analysis of the clinical and electrophysiologic characteristics of their abnormal movements is presented in this brief report. Data were analyzed between July 2015 and January 2018.Extensive upper spine instrumentation complicated with misalignment and prolonged postsurgical neuropathic pain.Video documentation of clinical and electrophysiologic characteristics of dancing dorsal quadrilaterals.Four patients with upper spine disease (2 women and 2 men, ranging in age from early 30s to early 70s) required extensive surgical manipulation and instrumentation that was complicated by misalignment, prolonged dorsal neuropathic pain, and unusual abnormal movements. These movements consisted of semirhythmic, repetitive writhing, and jerky movements of the scapular region with distinctive rotatory motions. They are referred to as the dancing dorsal quadrilaterals because they predominantly affected the bilateral trapezius and rhomboids (dorsal quadrilateral muscles) but could spread to adjacent muscles, and they are similar in appearance and possibly pathogenesis to "belly dancer" dyskinetic movements. The movements of the dancing dorsal quadrilaterals occur when upright but not when lying down or during voluntary muscle activation. Sensory stimulation also diminishes the movements. Long-duration bursts of normal motor unit potentials with normal recruitment pattern were evidenced.The dancing dorsal quadrilaterals syndrome represents a further example of a peripherally induced movement disorder characterized by neuropathic pain preceding a regional movement disorder following soft-tissue or nerve injury.