tbuckley/cabot-search huggingface dataset:
The TREatment of severe Atopic eczema Trial (TREAT)
Authors: A.D. Irvine, A.P. Jones, P. Beattie, S. Baron, F. Browne, F. Ashoor, L. O'Neill, A. Rosala-Hallas, T. Sach, C. Spowart, L. Taams, C. Walker, M. Wan, N. Webb, P. Williamson, C. Flohr
Journal: British Journal of Dermatology (2018)

Atopic eczema is a skin disease affecting around 20% of UK children, 16% of whom have moderate to severe disease. Severe atopic eczema can cause sleep disturbance, poor school attendance and social withdrawal, as well as attention‐deficit hyperactivity disorder, anxiety and clinical depression. Skin can become infected and this can be a reason for hospital admission. Although most cases of atopic eczema can be treated with emollients, topical anti‐inflammatory treatments and/or ultraviolet (UV) therapy, around 2% of children require oral (taken by mouth) immuno‐suppressive treatment. The main treatment options of this type (called systemic agents) are Ciclosporin (CyA) and Methotrexate (MTX) and there is concern about their potential short‐ and long‐term side effects. This article explains an upcoming clinical trial called “The TREatment of severe Atopic eczema Trial” (TREAT). TREAT addresses key clinical questions for the management of children with severe atopic eczema using systemic medication, in particular whether there is a difference in speed of onset (how long the drug takes to start working), effectiveness, side‐effect profile and reduction in flares post‐treatment between CyA and MTX, and the cost‐effectiveness of the drugs. Furthermore, TREAT examines how both drugs go about reducing inflammation in the body and on the skin. The study will involve 102 children aged 2 to 16 years.
α-Gal Syndrome vs Chronic Urticaria
Authors: Karlyn Pollack, Barrett J. Zlotoff, Larry C. Borish, Scott P. Commins, Thomas A. E. Platts-Mills, Jeffrey M. Wilson
Journal: JAMA Dermatology (2018)

α-Gal Syndrome vs Chronic UrticariaGalactose-α-1,3-galactose (α-gal) is an oligosaccharide expressed on glycoproteins and glycolipids of nonprimate mammals and is the causal epitope of an IgE-mediated allergy to mammalian meat. 1,2First reported in 2009, the α-gal syndrome is an increasingly appreciated problem across the southeastern United States and other parts of the world. 2 It is clear that tick bites, specifically relating to Amblyomma americanum (lone star tick), are causal in many, if not most, cases of α-gal sensitization in the United States. 3Following sensitization, many individuals will experience allergic symptoms on ingestion of meat or other products (eg, dairy) derived from nonprimate mammals.In contrast to typical IgE-mediated reactions, which occur within minutes of exposure, the α-gal allergy typically has a delayed onset of 2 to 6 hours. 2 The severity of the reaction varies from general urticaria to anaphylaxis, and individuals may not react to every exposure.Because of these atypical features, proper diagnosis can prove challenging.An epidemiological investigation of a pediatric population reported that α-gal may be misdiagnosed as recurrent urticaria or idiopathic anaphylaxis. 4While a recent report postulated that α-gal syndrome might represent a novel cause of chronic urticaria, further research failed to find such an association. 5,6Nevertheless, in areas where α-gal sensitization is prevalent, the potential for misdiagnosing cases of α-gal syndrome as chronic urticaria still exists.Here, we report cases labeled as chronic urticaria or chronic idiopathic urticaria within a cohort of patients in central Virginia being evaluated for α-gal syndrome.
Abstract P176: Impact of Serious Adverse Event Risks on the Cost-effectiveness of Intensive Blood Pressure Goals in Patients Aged ≥75 Years
Authors: Natalia Ruiz-Negron, Brandon K Bellows, Adam P Bress, Jordan B King, Rachel Hess, Srinivasan Beddhu, Zugui Zhang, Dan R Berlowitz, Mark A Supiano, William S Weintraub, Andrew E Moran
Journal: Circulation (2017)

Background: Compared to the overall Systolic Blood Pressure Intervention Trial (SPRINT) results, patients aged ≥75 years at baseline had a greater reduction in cardiovascular disease (CVD) events and all-cause mortality with an intensive systolic blood pressure (SBP) goal (&lt;120 mmHg) compared to a standard SBP goal (&lt;140 mmHg). Applying an intensive SBP goal in high-risk older patients represents a major shift in clinical practice and may increase concern for medication-related severe adverse events (SAEs). We hypothesized that the benefits of reduced CVD risk would outweigh the increased costs and SAE risk of intensive vs. standard SBP goals in SPRINT-eligible patients aged ≥75 years even when considering variable SAE risks. Methods: A microsimulation health-state transition model of 10,000 patients was created to estimate the CVD events, SAEs, quality-adjusted life years (QALYs), and direct healthcare costs of intensive vs. standard SBP goals. The model assumed patients were adherent to treatment during the median SPRINT follow-up, but that all patients would become non-adherent over 5 years. While adherent, CVD and SAE risks were derived from published SPRINT effect estimates for the ≥75 subgroup. Due to uncertainty in the SAE risk associated with intensive SBP goals in older adults, the intensive arm SAE risk was varied to determine the point at which treatment costs and harms outweighed CVD benefits at accepted willingness-to-pay thresholds. Healthcare costs and health state utilities were derived from national sources and other published estimates. Results: If SAE risk was equal to the observed rates in SPRINT, mean lifetime costs and QALYs were $268,000 and 7.85 for the intensive arm, and $262,000 and 7.60 for the standard arm. The resulting incremental cost-effectiveness ratio (ICER) was about $26,000 per QALY gained. However, as SAE risk in the intensive arm increased by 1.5, 2, and 2.5 times, the ICER increased to $33,000, $43,000, and $55,000 per QALY gained, respectively. Conclusion: Intensive SBP goals may be a cost-effective way to reduce CVD events and improve survival in patients aged ≥75 years, but safety and cost-effectiveness depend on medication-related SAE risk. However, these results are based on summary data and do not account for clustering of risks at the individual patient level. Thus, more precise prediction of risks and benefits is needed to guide selection of older patients for intensive SBP treatment goals.
Anatomy and Physiology of Primary Care Teams
Authors: Thomas Bodenheimer
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Professionalism, Performance, and the Future of Physician Incentives
Authors: Dhruv Khullar, Daniel Wolfson, Lawrence P. Casalino
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Consensus on molecular imaging and theranostics in prostate cancer
Authors: Stefano Fanti, Silvia Minozzi, Gerald Antoch, Ian Banks, Alberto Briganti, Ignasi Carrio, Arturo Chiti, Noel Clarke, Matthias Eiber, Johann De Bono, Karim Fizazi, Silke Gillessen, Sam Gledhill, Uwe Haberkorn, Ken Herrmann, Rodney J Hicks, Frederic Lecouvet, Rodolfo Montironi, Piet Ost, Joe M O'Sullivan, Anwar R Padhani, Jack A Schalken, Howard I Scher, Bertrand Tombal, R Jeroen A van Moorselaar, Heindrik Van Poppel, Hebert Alberto Vargas, Jochen Walz, Wolfgang A Weber, Hans-Jürgen Wester, Wim J G Oyen
Journal: The Lancet Oncology (2018)
Mucin Concentrations and Peripheral Airway Obstruction in Chronic Obstructive Pulmonary Disease
Authors: Mehmet Kesimer, Benjamin M. Smith, Agathe Ceppe, Amina A. Ford, Wayne H. Anderson, R. Graham Barr, Wanda K. O’Neal, Richard C. Boucher, Prescott G. Woodruff, MeiLan K. Han, Eric A. Hoffman, Fernando Martinez, Jeffrey L. Curtis, Robert Paine, Christopher B. Cooper, Eugene R. Bleecker
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

anti-tumor necrosis factor treatment.If previous Mtb exposure is diagnosed, chemoprophylaxis may be indicated to prevent active TB.Regarding the research implications, the host-pathogen interaction is finely balanced, with only a small subset of Mtbexposed individuals developing pulmonary disease to continue transmission (1, 4).The clinical observations that are emerging from the biologic treatment era provide entirely novel and highly relevant insights into human immune function and host-pathogen interactions.The increase in active TB after immune checkpoint inhibition suggests that excessive immunity may be just has harmful as insufficient immunity.Supporting this concept, Comstock and colleagues demonstrated in a study of 82,000 individuals that a strong response to TB antigens, which should be considered protective, actually associates with progression to active TB (8).Infection of mice deficient in PD-1 results in rapidly lethal inflammation (9, 10), consistent with a protective role in TB.Perhaps the most sobering implication is that it reinforces the finely balanced knife edge of the human-Mtb interaction.Simply driving an exaggerated immune response, without first defining determinants of progression versus protection in TB, risks inadvertently accelerating transmission and worsening the pandemic in the longer term (4).
Quantification of thioredoxin-1 by MALDI-TOF-MS using stable isotope labeled human thioredoxin-1.
Authors: Min He, Young-Mi Go, Matthew S. Reed, Jan Pohl, Dean P. Jones
Journal: Cancer Research (2005)

395  Thioredoxin-1 (Trx-1) is commonly overexpressed in cancer cells and has been applied as a target for anticancer therapy and a biomarker for prediction of cancer survival. However, quantitative methodology suitable for measurement of Trx-1 in clinical samples is not available. Therefore, in this study we developed a method to quantify the amount of Trx-1 using 13C, 15N-labeled recombinant human thioredoxin-1 as internal standard for Matrix Assisted Laser Desorption/Ionization (MALDI)- Time of Flight (TOF)- Mass spectrometry (MS). The stable isotope labeled Trx-1 was obtained from E.Coli following culture in medium containing 13C-glucose and 15N-ammonium chloride. The results from mass spectra showed all of the predicted fragments following digestion by trypsin for both the native and stable isotope labeled Trx-1. The method was validated by varying the amount of native and stable isotope labeled Trx-1, which showed that the height of peptide peaks changed accordingly. Moreover, the amount of Trx-1 analyzed by MALDI-TOF was consistent with that obtained from western blotting. Taken together, this method allows for high throughput quantitative analysis for clinical studies of the absolute amount and modification of Trx-1 in tumor cells as well as blood and tissues. Application of this method to tumor analysis could potentially enhance the specificity of cancer therapy by allowing use of Trx-1 targeted drugs for tumors with high Trx-1 expression.
NRF2 through RPS6 Activation Is Related to Anti-HER2 Drug Resistance in <i>HER2</i>-Amplified Gastric Cancer
Authors: Valentina Gambardella, Francisco Gimeno-Valiente, Noelia Tarazona, Carolina Martinez Ciarpaglini, Desamparados Roda, Tania Fleitas, Pablo Tolosa, Juan Miguel Cejalvo, Marisol Huerta, Susana Roselló, Josefa Castillo, Andrés Cervantes
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Despite the clinical advantage of the combination of trastuzumab and platinum-based chemotherapy in HER2-amplified tumors, resistance will eventually develop. The identification of molecular mechanisms related to primary and acquired resistance is needed. Experimental Design: We generated lapatinib- and trastuzumab-resistant clones deriving from two different HER2-amplified gastric cancer cell lines. Molecular changes such as protein expression and gene-expression profile were evaluated to detect alterations that could be related to resistance. Functional studies in vitro were corroborated in vivo. The translational relevance of our findings was verified in a patient cohort. Results: We found RPS6 activation and NRF2 to be related to anti-HER2 drug resistance. RPS6 or NRF2 inhibition with siRNA reduced viability and resistance to anti-HER2 drugs. In knockdown cells for RPS6, a decrease of NRF2 expression was demonstrated, suggesting a potential link between these two proteins. The use of a PI3K/TORC1/TORC2 inhibitor, tested in vitro and in vivo, inhibited pRPS6 and NRF2 expression and caused cell and tumor growth reduction, in anti–HER2-resistant models. In a cohort of HER2-amplified patients treated with trastuzumab and chemotherapy, a high level of NRF2 at baseline corresponds with worse progression-free survival. Conclusions: NRF2 through the PI3K/AKT/mTOR/RPS6 pathway could be a potential effector of resistance to anti-HER2 drugs in our models. RPS6 inhibition decreases NRF2 expression and restores sensitivity in HER2-amplified gastric cancer in vitro and in vivo. High NRF2 expression in gastric cancer patients predicts resistance to treatment. RPS6 and NRF2 inhibition could prevent resistance to anti-HER2 drugs.
INTERLEUKIN-10 IS PIVOTAL TO THE "DYSREGULATED" INFLAMMATORY RESPONSE OF ACUTE LIVER FAILURE
Authors: Charalambos G. Antoniades, Philip A. Berry, Ivana Carey, Serena Longhi, Timothy J. Cross, Munther J. Hussain, Alberto Quaglia, Julia Wendon, Diego Vergani
Journal: Hepatology (2008)
Simulating Inflammation in a Wound Microenvironment Using a Dermal Wound‐on‐a‐Chip Model
Authors: Sahar Biglari, Thi Y. L. Le, Richard P. Tan, Steven G. Wise, Alessandro Zambon, Gaia Codolo, Marina De Bernard, Majid Warkiani, Aaron Schindeler, Sina Naficy, Peter Valtchev, Ali Khademhosseini, Fariba Dehghani
Journal: Advanced Healthcare Materials (2018)

Abstract Considerable progress has been made in the field of microfluidics to develop complex systems for modeling human skin and dermal wound healing processes. While microfluidic models have attempted to integrate multiple cell types and/or 3D culture systems, to date they have lacked some elements needed to fully represent dermal wound healing. This paper describes a cost‐effective, multicellular microfluidic system that mimics the paracrine component of early inflammation close to normal wound healing. Collagen and Matrigel are tested as materials for coating and adhesion of dermal fibroblasts and human umbilical vein endothelial cells (HUVECs). The wound‐on‐chip model consists of three interconnecting channels and is able to simulate wound inflammation by adding tumor necrosis factor alpha (TNF‐α) or by triculturing with macrophages. Both the approaches significantly increase IL‐1β, IL‐6, IL‐8 in the supernatant ( p &lt; 0.05), and increases in cytokine levels are attenuated by cotreatment with an anti‐inflammatory agent, Dexamethasone. Incorporation of M1 and M2 macrophages cocultured with fibroblasts and HUVECs leads to a stimulation of cytokine production as well as vascular structure formation, particularly with M2 macrophages. In summary, this wound‐on‐chip system can be used to model the paracrine component of the early inflammatory phase of wound healing and has the potential for the screening of anti‐inflammatory compounds.
Annals Story Slam - Baby Code White
Authors: Lesley Wiesenfeld
Journal: Annals of Internal Medicine (2018)

Web Exclusives4 December 2018Annals Story Slam - Baby Code WhiteFREELesley Wiesenfeld, MDLesley Wiesenfeld, MDUniversity of Toronto and Mt. Sinai Hospital, Toronto, Ontario, Canada (L.W.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W18-0029 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Baby Code White "Baby Code White," by Lesley Wiesenfeld, MD (Duration 7:19)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of Toronto and Mt. Sinai Hospital, Toronto, Ontario, Canada (L.W.)Current Author Address: Lesley Wiesenfeld, MD; e-mail, lesley.[email protected]ca. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 December 2018Volume 169, Issue 11Page: SS1 ePublished: 4 December 2018 Issue Published: 4 December 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.Loading ...
Biomarker-driven strategy for MCL1 inhibition in T-cell lymphomas
Authors: Raphael Koch, Amanda L. Christie, Jennifer L. Crombie, Adam C. Palmer, Deborah Plana, Kay Shigemori, Sara N. Morrow, Alexandria Van Scoyk, Wenchao Wu, Elizabeth A. Brem, J. Paul Secrist, Lisa Drew, Alwin G. Schuller, Justin Cidado, Anthony Letai, David M. Weinstock
Journal: Blood (2018)
Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor–experienced adult patients with PNH: the 302 study
Authors: Austin G. Kulasekararaj, Anita Hill, Scott T. Rottinghaus, Saskia Langemeijer, Richard Wells, F. Ataulfo Gonzalez-Fernandez, Anna Gaya, Jong Wook Lee, Emilio Ojeda Gutierrez, Caroline I. Piatek, Jeff Szer, Antonio Risitano, Shinji Nakao, Eric Bachman, Lori Shafner, Andrew I. Damokosh, Stephan Ortiz, Alexander Röth, Regis Peffault de Latour
Journal: Blood (2018)
Abstract MP37: Diet Quality and Lifetime Risk of Total Cardiovascular Disease in US Adults
Authors: Victor W Zhong, Hongyan Ning, Linda V Van Horn, John T Wilkins, Donald M Lloyd-Jones, Norrina B Allen
Journal: Circulation (2018)

Introduction: Suboptimal diet is a leading risk factor for cardiovascular disease (CVD). Yet, the relationship between diet quality and lifetime CVD risk, and whether it differs by age, are unclear. Methods: Diet data from 10 US prospective cohorts were harmonized according to a standard protocol. Three diet quality indices were calculated within each cohort: Dietary Approaches to Stop Hypertension (DASH) diet, alternate Healthy Eating Index 2010 (aHEI-2010), and alternate Mediterranean (aMED) diet. CVD included coronary heart disease, stroke and heart failure. Study sample was divided into younger (&lt;40 years old), middle-aged (40-60) and older (&gt;60) groups based on age at the first dietary assessment. Cumulative CVD risk according to 5-year interval was estimated using modified Kaplan-Meier analysis, adjusting for competing risk of death. Multivariable proportional hazards regression was applied to determine the association between the three diet quality indices and CVD by sex and age. Results: A total of 129,892 participants with 1,603,199 person years of follow-up were analyzed. The adjusted cumulative CVD risk was lower in younger and middle-aged men and all women who had higher DASH score (Figure 1). Age modified the diet-CVD association in both men and women (P &lt;0.0005). Compared to the lowest DASH score quintile (poorest diet), the adjusted hazard ratio (HR) for CVD decreased with increasing quintile of diet quality. The HR for the highest quintile was 0.41 (95% CI: 0.20-0.87) in younger men, 0.97 (0.82-1.16) in middle-aged men, 1.03 (0.89-1.19) in older men, 0.47 (0.21-1.05) in younger women, 0.73 (0.63-0.84) in middle-aged women, and 0.82 (0.76-0.88) in older women. Results were similar for aMED and aHEI-2010 score. Conclusions: Better diet quality is associated with lower lifetime CVD risk in all women and men except older men. Stronger inverse diet quality-CVD association in younger than middle-aged and older adults suggests that relative benefits of a healthy diet for CVD risk reduction may be greater at younger ages.