tbuckley/cabot-search huggingface dataset:
Development of a gene expression-based test for the detection of endometrial cancer in uterine aspirates.
Authors: E. Rosell, C. Pérez, A. Ortega, C. Nieto, A. Doll, A. Gil, J. Ponce, M. Abal, J. Reventós, T. Maes
Journal: Journal of Clinical Oncology (2010)

5066 Background: We report the development of a gene expression (GE) based test to detect endometrial cancer (EC). Validation of the test in a multicenter validation study conducted in over 10 different hospitals in Spain is ongoing. Methods: Discovery: Seventy tissue samples (60 EC + 10 normal) were collected from women with abnormal uterine bleeding (AUB) that were submitted to biopsy or tumor resection. Microarray based GE analysis was performed at Oryzon to yield a candidate gene set. Initial validation: An independent cohort of normal (n = 20) and tumor tissue (n = 20) samples as well normal (n = 48) and tumor (n = 33) uterine aspirate samples was obtained for validation. GE analysis was performed using TaqMan LDAs containing an EC-specific signature in a 64-gene assay format. Expression profiles from 9 tumor tissue and aspirates from the same patients were compared. ROC scores of the individual markers as secretory/proliferative and/or tumor/no tumor markers were assessed. The best markers and endogenous controls were selected and 5 test score algorithms (4, 5, 6, 12, 20 genes) developed. Multi-center validation: a cohort of 350-500 patients with AUB (20% is expected of being affected by EC) is being enrolled in a multicentric double blind study to evaluate the 5 test algorithms. Results: The 5 scoring algorithms classified the 81 aspirates from subjects in the validation cohort as positive or negative for EC with high specificities and sensitivities (near 100%). Inclusion of markers that distinguish between secretory and proliferative phase is essential to correctly diagnose pre or perimenopausal women. One sample recorded a negative on histologic basis was classified as tumor according to our algorithms. Histologic revision of the EC-negative sample led to a reclassification of the sample, which may indicate that the GE assay could reduce diagnostic errors. Conclusions: The uterine aspirate based GE test shows high diagnostic potential. Inclusion of EC subtype specific and prognostic marker is expected to further increase the utility of the proposed diagnostic method. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Grupo Reig Jofré, Hospital Bellvitge, Hospital Vall d'Hebron, Oryzon Genomics SA Oryzon Genomics SA
Junior doctors’ strike next week is suspended, BMA announces
Authors: Abi Rimmer
Journal: BMJ (2016)

The BMA has decided to suspend planned industrial action by junior doctors in England next week, after discussions with NHS England.

The BMA said that although it had provided more than the legally required seven days’ notice ahead of industrial action, NHS England had said that it needed more time to plan for the escalated action.

Earlier this month the BMA …
Performance of the Tobacco, Alcohol, Prescription Medication, and Other Substance Use (TAPS) Tool for Substance Use Screening in Primary Care Patients
Authors: Jennifer McNeely, Li-Tzy Wu, Geetha Subramaniam, Gaurav Sharma, Lauretta A. Cathers, Dace Svikis, Luke Sleiter, Linnea Russell, Courtney Nordeck, Anjalee Sharma, Kevin E. O'Grady, Leah B. Bouk, Carol Cushing, Jacqueline King, Aimee Wahle, Robert P. Schwartz
Journal: Annals of Internal Medicine (2016)

Background: Substance use, a leading cause of illness and death, is underidentified in medical practice. Objective: The Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) tool was developed to address the need for a brief screening and assessment instrument that includes all commonly used substances and fits into clinical workflows. The goal of this study was to assess the performance of the TAPS tool in primary care patients. Design: Multisite study, conducted within the National Drug Abuse Treatment Clinical Trials Network, comparing the TAPS tool with a reference standard measure. (ClinicalTrials.gov: NCT02110693) Setting: 5 adult primary care clinics. Participants: 2000 adult patients consecutively recruited from clinic waiting areas. Measurements: Interviewer- and self-administered versions of the TAPS tool were compared with a reference standard, the modified World Mental Health Composite International Diagnostic Interview (CIDI), which measures problem use and substance use disorder (SUD). Results: Interviewer- and self-administered versions of the TAPS tool had similar diagnostic characteristics. For identifying problem use (at a cutoff of 1+), the TAPS tool had a sensitivity of 0.93 (95% CI, 0.90 to 0.95) and specificity of 0.87 (CI, 0.85 to 0.89) for tobacco and a sensitivity of 0.74 (CI, 0.70 to 0.78) and specificity of 0.79 (CI, 0.76 to 0.81) for alcohol. For problem use of illicit and prescription drugs, sensitivity ranged from 0.82 (CI, 0.76 to 0.87) for marijuana to 0.63 (CI, 0.47 to 0.78) for sedatives; specificity was 0.93 or higher. For identifying any SUD (at a cutoff of 2+), sensitivity was lower. Limitations: The low prevalence of some drug classes led to poor precision in some estimates. Research assistants were not blinded to participants' TAPS tool responses when they administered the CIDI. Conclusion: In a diverse population of adult primary care patients, the TAPS tool detected clinically relevant problem substance use. Although it also may detect tobacco, alcohol, and marijuana use disorders, further refinement is needed before it can be recommended broadly for SUD screening. Primary Funding Source: National Institute on Drug Abuse.
Effects of Social Needs Screening and In-Person Service Navigation on Child Health
Authors: Laura M. Gottlieb, Danielle Hessler, Dayna Long, Ellen Laves, Abigail R. Burns, Anais Amaya, Patricia Sweeney, Christine Schudel, Nancy E. Adler
Journal: JAMA Pediatrics (2016)

Social determinants of health shape both children's immediate health and their lifetime risk for disease. Increasingly, pediatric health care organizations are intervening to address family social adversity. However, little evidence is available on the effectiveness of related interventions.To evaluate the effects of social needs screening and in-person resource navigation services on social needs and child health.Patients were randomized to intervention or active control conditions by the day of the week. Primary outcomes observed at 4 months after enrollment included caregivers' reports of social needs and child health status. Recruitment occurred between October 13, 2013, and August 27, 2015, in pediatric primary and urgent care clinics in 2 safety-net hospitals. Participants were English-speaking or Spanish-speaking caregivers accompanying minor children to nonacute medical visits.After standardized screening, caregivers either received written information on relevant community services (active control) or received in-person help to access services with follow-up telephone calls for further assistance if needed (navigation intervention).Change in reported social needs and in caregiver assessment of child's overall health reported 4 months later.Among 1809 patients enrolled in the study, evenly split between the 2 sites, 31.6% (n = 572) were enrolled in a primary care clinic and 68.4% (n = 1237) were enrolled in an urgent care setting. The children were primarily Hispanic white individuals (50.9% [n = 921]) and non-Hispanic black individuals (26.2% [n = 473]) and had a mean (SD) age of 5.1 (4.8) years; 50.5% (n = 913) were female. The reported number of social needs at baseline ranged from 0 to 11 of 14 total possible items, with a mean (SD) of 2.7 (2.2). At 4 months after enrollment, the number of social needs reported by the intervention arm decreased more than that reported by the control arm, with a mean (SE) change of -0.39 (0.13) vs 0.22 (0.13) (P < .001). In addition, caregivers in the intervention arm reported significantly greater improvement in their child's health, with a mean (SE) change of -0.36 (0.05) vs -0.12 (0.05) (P < .001).To our knowledge, this investigation is the first randomized clinical trial to evaluate health outcomes of a pediatric social needs navigation program. Compared with an active control at 4 months after enrollment, the intervention significantly decreased families' reports of social needs and significantly improved children's overall health status as reported by caregivers. These findings support the feasibility and potential effect of addressing social needs in pediatric health care settings.clinicaltrials.gov Identifier: NCT01939704.
Case 51-1969
Authors: John D. Stoeckle, Austin L. Vickery
Journal: New England Journal of Medicine (1969)

Presentation of CaseAn eighty-one-year-old woman was admitted to the hospital because of hemoptysis.For the previous four months she had had gradually increasing anorexia, weight loss and weakness. An x-ray film of the chest taken two months before admission (Fig. 1) showed an infiltrate in the right middle lobe, with slight loss of volume of the lobe; on a lateral film a 13-mm nodular shadow was visible in the region of the superior segment of one of the lower lobes (Fig. 2); the remainder of the lungs was clear; the cardiac silhouette and pulmonary vasculature were normal. One week . . .
Oral Cryotherapy for Preventing Oral Mucositis in Patients Receiving Cancer Treatment
Authors: Philip Riley, Martin G. McCabe, Anne-Marie Glenny
Journal: JAMA Oncology (2016)

<h3>Clinical Question</h3> In patients receiving treatment for cancer, does oral cryotherapy prevent oral mucositis? <h3>Bottom Line</h3> Oral cryotherapy is effective for the prevention of oral mucositis in adults receiving fluorouracil-based chemotherapy for solid cancers, and for the prevention of severe oral mucositis in adults receiving high-dose melphalan-based chemotherapy before hematopoietic stem cell transplantation (HSCT).
Unnecessary angiography could be reduced by using non-invasive imaging, study finds
Authors: Jacqui Wise
Journal: BMJ (2016)

Unnecessary angiography could be reduced in patients with suspected coronary heart disease by using non-invasive imaging rather than following the current UK guidelines, a study in JAMA has concluded.1

Invasive coronary angiography has been commonly used early in diagnostic pathways in patients with suspected coronary heart disease even though evidence has shown that most patients presenting with chest pain will not have significant obstructive coronary disease.

The randomised controlled trial compared non-invasive cardiovascular magnetic resonance …
Radiologic progression types are treatment specific: An exploratory analysis of a phase 3 study of bevacizumab <i>plus</i> radiotherapy <i>plus</i> temozolomide for patients with newly diagnosed glioblastoma (AVAglio).
Authors: Martha Nowosielski, Olivier L. Chinot, Alexander Radbruch, Guenther Stockhammer, Josep Garcia, Cedric Revil, Ryo Nishikawa, Warren P. Mason, Roger Henriksson, Frank Saran, Martin Bendszus, Lauren E. Abrey, Timothy Francis Cloughesy, Wolfgang Wick
Journal: Journal of Clinical Oncology (2016)

2048 Background: Thetype of radiological progression following bevacizumab treatment failure is related to outcome in patients with progressive glioblastoma. In an exploratory analysis of the randomized, placebo-controlled phase III clinical trial in newly diagnosed glioblastoma of bevacizumab (bev) plus radiotherapy/temozolomide (AVAglio) we aimed to investigate whether these progression types (PT) are induced by therapy (anti-angiogenic versus sole cytotoxic chemotherapy), are related to outcome and may therefore reflect a particular resistance mechanism. Methods: MRI scans (baseline until IRF progress) of 621 patients (bev arm, n = 299; placebo arm, n = 322) were available for analysis in sufficient detail and quality. PT were categorized according to contrast enhancement behavior in T1 and T2 hyper-intense signal change as published before (Nowosielski et al, Neurology 2014). Frequencies of the 5 PTs (cT1 flare-up, classic T1 progress, T2-diffuse, T2-circumscribed and primary non-responder), time to development (PFS) and overall survival (OS) were assessed within each treatment arm. Results: Classic T1 progress and primary non responder were more common in the placebo than in the bev arm (56.8 % versus 25.1% and 21.7% versus 3.3%, respectively.) In the bev arm, cT1 flare up and the T2 circumscribed PT were more common (37.5% versus 10.9% and 21.7%. versus 3.4%, respectively). T2 diffuse was equally distributed between the treatment arms and showed longer PFS compared to the other PTs in both arms. In the bev arm, cT1 flare up as well as T2 diffuse showed longer OS than all the other PTs (17.8 months vs median in T2 diffuse not yet reached). Conclusions: Exploratory analysis of AVAglio imaging data showed that radiologic progression types seem to be specific for anti-angiogenic or temozolomide treatment failure. These progression types show differences in PFS and OS and may therefore reflect a particular resistance mechanism that may guide further post progression therapy. Clinical trial information: NCT00943826.
The Treatment of Mild Hypertension Study
Authors: Kamyar Safdari
Journal: JAMA (1993)

<h3>To the Editor.</h3> —Neaton et al<sup>1</sup>reported that the use of combined pharmacologic and nonpharmacologic intervention is more efficacious and equally safe in the treatment of mild hypertension than nonpharmacologic interventions alone. In a report of the study design,<sup>2</sup>TOMHS investigators included cigarette smoking among "etiologically significant major risk factors" for coronary heart disease and cited Multiple Risk Factor Intervention Trial data, which illustrated the increased rate of coronary heart disease mortality among smokers. An article characterizing TOMHS participants<sup>3</sup>reported that 10.9% were cigarette smokers. A subsequent article<sup>4</sup>reporting results through the first 12 months of the study indicated that cigarette smokers were proportionately randomized to treatment and placebo groups. The TOMHS investigators did not comment on whether sustained nutritional-hygienic advice to reduce weight, dietary sodium intake, and alcohol intake, and to increase physical activity was accompanied by advice to smokers that they should stop smoking.
Assessing Cartilage Biomechanical Properties: Techniques for Evaluating the Functional Performance of Cartilage in Health and Disease
Authors: Benjamin A. Lakin, Brian D. Snyder, Mark W. Grinstaff
Journal: Annual Review of Biomedical Engineering (2017)

Osteoarthritis (OA) affects millions of people and results in weakened hyaline cartilage due to overloading. During joint articulation, hyaline cartilage must withstand high loads while maintaining low friction to prevent wear and tissue loss. Thus, cartilage compressive stiffness and the coefficient of friction are important indicators of the tissue's functional performance. These mechanical properties are often measured ex vivo using mechanical testing regimens, but arthroscopic handheld probes (e.g., for indentation testing, ultrasound, and optical coherence tomography) and noninvasive imaging modalities (e.g., magnetic resonance imaging and computed tomography) provide opportunities for either direct or indirect in vivo assessment of cartilage mechanical properties. In this review, we examine the application of these techniques for evaluating cartilage, with a focus on measuring mechanical properties for early-stage OA diagnosis. For each approach, we discuss the advantages, disadvantages, current and potential clinical utility, and promising technological improvement.
Echocardiographic variables as prognostic indicators and therapeutic monitors in chronic congestive heart failure: Veterans affairs cooperative studies V-HeFT I and II
Authors: Maylene Wong, Gary Johnson, Ralph Shabetai, Vincent Hughes, Geetha Bhat, Becky Lopez, Jay N. Cohn
Journal: Circulation (1993)

Background. Echocardiographic indexes of ventricular function have become indispensable in clinical cardiology but have not been tested as prognostic markers or therapeutic monitors in clinical trials. In two Veterans Administration trials on heart failure (Vasodilator-Heart Failure Trials I and II, V-HeFT I and II), echocardiographic variables were analyzed as predictors and monitors and were compared with other indicators of cardiac peformance. Methods and Results. Echocardiograms were recorded before randomization and at follow-up intervals
Reduced Affinity To VWF Induced By a Novel Mutation At Pro1809Leu (factor VIII-Tenri) Is The Cause Of Mild Hemophilia A Developing Anti-Factor VIII Inhibitor
Authors: Koji Yada, Keiji Nogami, Masahiro Takeyama, Hiroaki Minami, Philip J. Fay, Midori Shima
Journal: Blood (2013)
Proresolving lipid mediators resolvin D1, resolvin D2, and maresin 1 are critical in modulating T cell responses
Authors: Valerio Chiurchiù, Alessandro Leuti, Jesmond Dalli, Anders Jacobsson, Luca Battistini, Mauro Maccarrone, Charles N. Serhan
Journal: Science Translational Medicine (2016)

Specialized proresolving lipid mediators reduce human T cell activation and prevent T H 1 and T H 17 cell differentiation from naïve T cells while promoting de novo T reg induction.
Cooperation Between the CD20 Receptor and hIFN-Alpha Receptor in Overriding the Blocked CD20 Cell-Signaling in Rituximab-Resistant B-NHL By the Fusion Protein Anti-CD20-hIFN-Alpha
Authors: Gabriel G Vega, Luz A Franco-Cea, Sara Huerta-Yepez, Hector Mayani, Otoniel Martinez-Maza, Benjamin Bonavida, Mario I. Vega
Journal: Blood (2015)
Abstract 11938: Long-term Population-based Outcomes of Novel Oral Anticoagulants Compared to Warfarin Among Long-term Anticoagulated Patients: A Propensity Matched Analysis
Authors: Victoria Jacobs, Heidi T May, Tami L Bair, Jeffrey L Anderson, Brian G Crandall, Michael Cutler, John D Day, Charles D Mallender, Jeffrey S Osborn, Scott M Stevens, J P Weiss, Scott C Woller, T J Bunch
Journal: Circulation (2015)

Introduction: Novel oral anticoagulants (NOACs) have been used in clinical practice in the US for the last 4 years. While NOACs may be an attractive alternative to warfarin among many patients, long-term outcomes of use of these medications are unknown. We performed a propensity matched analysis of long-term outcomes among patients taking a NOAC or warfarin. Hypothesis: NOACs will be superior to warfarin for the reduction of long-term outcomes. Methods: Patients receiving long-term anticoagulation between June 2010 and December 2014 for thromboembolism prevention with either warfarin or a single NOAC were matched 1:1 by index date (± 6 months) and propensity score (±0.01). Multivariable Cox hazard regression was performed to determine the risk of death, stroke/TIA, major bleed, and bleed by the anticoagulant therapy received. Results: Patients studied included: apixaban: 590, dabigatran: 583, rivaroxaban: 1, 454. A total of 5,254 patients were studied (2,627 per group). Average age was 72.4±10.9 and 59.0% were male. The majority of patients were receiving long-term anticoagulation for AF management (warfarin: 96.5% vs. NOAC: 92.7%, p&lt;0.0001). Rivaroxaban (n=1,454 [55.3%]) was the most commonly used NOAC, (apixaban=590 [22.5%], dabigatran=583 [22.2%]). History of stroke/TIA and prior bleed were similar between the groups, yet more NOAC patients formally had major bleeding (9.2% vs. 6.8%, p=0.002). The use of NOACs compared to warfarin were associated with a reduced risk of long-term adverse outcomes [Figure, death (p=0.09), stroke/TIA (p&lt;0.0001), major bleed (p&lt;0.0001), and bleed (p=0.14)]. No significant outcome variance was noted in NOAC type comparison. Conclusions: Our community-based results are support better long-term efficacy and safety of NOACs compared to warfarin, and are in agreement with the shorter-term results of previous clinical trials.
Transcriptomic analysis of skin in a case of ichthyosis Curth-Macklin caused by a<i>KRT1</i>mutation
Authors: O. Ortega-Recalde, D. Silgado, C. Fetiva, D.J. Fonseca, P. Laissue
Journal: British Journal of Dermatology (2016)

Ichthyosis Curth–Macklin (ICM) can be considered one of the most drastic forms of genetically-derived keratin disease. Individuals suffering from ICM mainly display severe palmoplantar keratoderma and dark spiky plaques which may affect the entire body.

This article is protected by copyright. All rights reserved.
OXIDATIVE STRESS MODULATES HEME LEVELS and INDUCES PEROXIREDOXIN-2 IN β THALASSEMIC ERYTHROPOIESIS as NOVEL CYTOPROTECTIVE RESPONSE
Authors: Lucia De Franceschi, Mariarita Bertoldi, Maria Domenica Cappellini, Luigia De Falco, Sara Santos Franco, Luisa Ronzoni, Francesco Turrini, Alessandra Colancecco, Clara Camaschella, Achille Iolascon
Journal: Blood (2010)
Adalimumab in Patients with Active Noninfectious Uveitis
Authors: Glenn J. Jaffe, Andrew D. Dick, Antoine P. Brézin, Quan Dong Nguyen, Jennifer E. Thorne, Philippe Kestelyn, Talin Barisani-Asenbauer, Pablo Franco, Arnd Heiligenhaus, David Scales, David S. Chu, Anne Camez, Nisha V. Kwatra, Alexandra P. Song, Martina Kron, Samir Tari, Eric B. Suhler
Journal: New England Journal of Medicine (2016)

Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis.This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported.The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years).In our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo. (Funded by AbbVie; VISUAL I ClinicalTrials.gov number, NCT01138657 .).
P0222 : Relevance of organic cation transporter OCT1 (SLC22A1) in diethylnitrosamine-initiated and phenobarbital-promoted hepatocellular carcinoma in OCT3-knockout mice
Authors: J. Knapstein, P. Fuchs, D. Grimm, A. Lautem, M. Hoppe-Lotichius, M.A. Woerns, H. Lang, P.R. Galle, T. Zimmermann
Journal: Journal of Hepatology (2015)
Generation of an in vitro 3D PDAC stroma rich spheroid model
Authors: Matthew J. Ware, Vazrik Keshishian, Justin J. Law, Jason C. Ho, Carlos A. Favela, Paul Rees, Billie Smith, Sayeeduddin Mohammad, Rosa F. Hwang, Kimal Rajapakshe, Cristian Coarfa, Shixia Huang, Dean P. Edwards, Stuart J. Corr, Biana Godin, Steven A. Curley
Journal: Biomaterials (2016)