tbuckley/cabot-search huggingface dataset:
Updated results of a phase 1 study of EGF816, a third-generation, mutant-selective EGFR tyrosine kinase inhibitor (TKI), in advanced non-small cell lung cancer (NSCLC) harboring T790M.
Authors: Daniel Shao-Weng Tan, James Chih-Hsin Yang, Natasha B. Leighl, Gregory J. Riely, Lecia V. Sequist, Enriqueta Felip, Takashi Seto, Juergen Wolf, Susan Elizabeth Moody, Kenneth Adams, Shu-Fang Hsu Schmitz, Eugene Y. Tan, Dong-Wan Kim
Journal: Journal of Clinical Oncology (2016)

9044 Background: Up to 60% of patients (pts) with NSCLC harboring an activating EGFR mutation (mut) and treated with a first-generation EGFR TKI develop a secondary gatekeeper T790M mut. EGF816 is an irreversible EGFR TKI that is highly potent against activating mut (L858R, ex19del) and T790M mut, while sparing wild-type EGFR. Methods: Pts with NSCLC with locally or centrally confirmed T790M status were enrolled in this multicenter, dose-escalation study to determine the safety, tolerability, and antitumor activity of EGF816 (NCT02108964). EGF816 was administered in capsule or tablet form on a continuous 28-day schedule. Dose escalation began at 75 mg QD and was guided by adaptive Bayesian logistic regression models to determine the maximum tolerated dose. Results: As of 30 Sept 2015, 132 pts had been treated (104 capsule; 28 tablet) across 7 dose levels (75, 150, 225, 300, and 350 mg QD for capsules; 100, 150, 200, and 225 mg QD for tablets), with median age 61.5 (range 32-82) years, 36% male, and 64% Asian. At the 15 June 2015 cutoff, 111 pts were evaluable for safety; 4 pts at ≥ 225 mg had a dose-limiting toxicity. The most common AEs regardless of study drug relationship ( > 20%) were diarrhea (40%), maculopapular rash (39%), pruritus (32%), dry skin (23%), stomatitis (23%), and fatigue (21%); the most common grade 3/4 AEs ( > 5%) were maculopapular rash (14%), anemia (6%), and diarrhea (6%). Hepatitis B reactivation occurred in 2 pts who were not on antiviral prophylaxis; 1 pt resumed EGF816 after starting entecavir, 1 pt died. At the 30 Sept 2015 cutoff, 127 pts were evaluable for response. The confirmed ORR was 44% (56/127, with an additional 11 responders awaiting confirmation) and disease control rate was 91%. The Kaplan-Meier (KM) estimate of median duration of response in confirmed responders was 9.2 mo. With disease progression in 38 pts and 5 deaths without disease progression, the median KM estimate of PFS was 9.2 mo (95% CI 9.0-NE). Conclusions: EGF816 is well tolerated with a manageable safety profile. Durable antitumor activity against EGFR T790M mut NSCLC was observed. Further study is ongoing to establish the optimal dose and formulation. Clinical trial information: NCT02108964.
The War Is Not Yet Won
Authors: Laura A. Young, John B. Buse
Journal: Diabetes Care (2017)

In this issue of Diabetes Care , Selvin and Ali (1) have done a masterful job of exploring and explaining both the rise in the incidence of diabetes over 20 years and the fall in the incidence of diabetes over the last 5 years in the U.S. You may want to skip this and just read their article. The bottom line is that we as clinicians can confirm that they, as epidemiologists, have almost certainly gotten it right. Importantly, their analysis has critical implications for policy makers.

There are a couple of critical definitions that need to be clarified. First, the term “incidence” refers to an annual rate of new diagnoses. That is the feature of diabetes explored in this article and here refers specifically to the number of people who report in a survey that a health care professional told them for the first time that they had diabetes in the last year. That number has dropped about 20% since 2009 (2). Incidence needs to be distinguished from “prevalence,” which refers to the number or proportion affected by a condition. For diabetes, that is a number that continues to rise and is only peripherally addressed (3).

While clinicians tend to not focus on research methodology, in this case the methods are crucial to understand. The data from which incidence rates are derived is national survey data. These data …
Human CD34+ Cells from Different Sources Disclose a Specific Stemness Signature
Authors: Maria Rosa Lidonnici, Annamaria Aprile, Marta Frittoli, Giacomo Mandelli, Ylenia Paleari, Antonello Spinelli, Bernhard Gentner, Matilde Zambelli, Cristina Parisi, Laura Bellio, Elena Cassinerio, Laura Zanaboni, Maria Domenica Cappellini, Fabio Ciceri, Sarah Marktel, Giuliana Ferrari
Journal: Blood (2016)
Abstract 035: Effects of Canola Oil and High Oleic Canola Oil-rich Diets on Abdominal Fat Mass in Individuals at Risk for Metabolic Syndrome
Authors: Xiaoran Liu, Penny M Kris-Etherton, Sheila G West, Benoit Lamarche, David J Jenkins, Jennifer A Fleming, Cindy E McCrea, Patrick Couture, Shuaihua Pu, Peter J Jones
Journal: Circulation (2013)

Introduction:  Dietary monounsaturated fatty acids (MUFA) decrease metabolic syndrome (MetS) risk factors. Therefore, novel vegetable oils high in MUFA may improve CVD risk in individuals with MetS.   Objective:  To evaluate the efficacy of five vegetable oil treatments including corn/safflower oil (69.3% LA, 17.6% MUFA), canola oil (62.8% MUFA, 29.3% PUFA: 19.5% LA, 10% ALA), high oleic canola oil (72% MUFA, 17% PUFA: 15% LA, 2% ALA), high oleic canola oil with DHA (63.8% MUFA, 13% LA, 6% DHA), and flax/safflower oil (69.4% PUFA: 37.5% LA, 32% ALA, 17.9% MUFA) on abdominal fat mass in subjects with central obesity plus at least one other risk factor for MetS.   Methods:  A multi-center, double blind, randomized, 5-period crossover, controlled feeding study was conducted to evaluate the effects of vegetable oils with different fatty acid profiles on abdominal fat mass in subjects with risk factors for MetS. Subjects (n=121: 62 women, 59 men) were fed an isocaloric heart healthy diet (50% CHO, 15% PRO, 35% FAT,    Results:  A mixed linear model demonstrated that canola and high oleic canola oils reduced abdominal fat mass by 1.6% (51.4 g) and 1.6% (50.1 g), respectively. These changes across treatments were significantly different from flax/safflower oil (p   Conclusion:  Canola oil and high oleic canola oil lowered abdominal fat mass compared to flax/safflower oil after 4 weeks in men and women with metabolic syndrome risk factors consuming an isocaloric diet. Further studies are needed to determine the mechanisms that account for the visceral fat loss in response to a high MUFA diet.
Biologic Significance of the Tolerance Dose in X-Ray and Radium Protection
Authors: Paul S. Henshaw
Journal: JNCI Journal of the National Cancer Institute (1941)

Biologic Significance of the Tolerance Dose in X-Ray and Radium Protection Paul S. Henshaw Paul S. Henshaw research fellow National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 1, Issue 6, June 1941, Pages 789–805, https://doi.org/10.1093/jnci/1.6.789 Published: 01 June 1941
Ultrathin, bioresorbable polymer sirolimus-eluting stents versus thin, durable polymer everolimus-eluting stents in patients undergoing coronary revascularisation (BIOFLOW V): a randomised trial
Authors: David E Kandzari, Laura Mauri, Jacques J Koolen, Joseph M Massaro, Gheorghe Doros, Hector M Garcia-Garcia, Johan Bennett, Ariel Roguin, Elie G Gharib, Donald E Cutlip, Ron Waksman
Journal: The Lancet (2017)
“Birdbrains” should not be ignored in studying the evolution of <i>g</i>
Authors: Irene M Pepperberg
Journal: Behavioral and Brain Sciences (2017)

Abstract The authors evaluate evidence for general intelligence ( g ) in nonhumans but lean heavily toward mammalian data. They mention, but do not discuss in detail, evidence for g in nonmammalian species, for which substantive material exists. I refer to a number of avian studies, particularly in corvids and parrots, which would add breadth to the material presented in the target article.
OP0003 Rheumatic immune related adverse events of checkpoint therapy for cancer: case series of an emerging nosologic entity
Authors: C Calabrese, E Kirchner, A Kontzias, V Velcheti, L Calabrese
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Immune checkpoint therapy is a major advance in the field of oncology. Agents targeting CTLA-4, programmed cell death protein 1 (PD-1) and PD-ligand 1 have produced significant survival benefits in patients with malignancies. With these therapies have come a unique spectrum of adverse events related to over-activation of the immune system with resultant autoimmune disease. To date reports of rheumatic immune related AEs (irAEs) have not been adequately characterized, as they are infrequently reported in clinical trials. We describe the largest series of rheumatic irAEs secondary to checkpoint inhibitors to date. <h3>Objectives</h3> To report our 22 month experience with 19 patients evaluated in the Cleveland Clinic Rheumatology department. <h3>Methods</h3> A retrospective chart review was performed on 19 patients, 16 without pre-existing autoimmune disease (AID) and 3 with pre-existing AID, seen in our rheumatology department February 2015-December 2016. 2 designated rheumatologists evaluated all patients. Recorded information included gender, age, age at malignancy diagnosis, malignancy details, checkpoint inhibitor, nature of rheumatic irAE, time of onset, diagnostic data, treatment of irAE and response to treatment. <h3>Results</h3> In the group without pre-existing AID 56% developed a rheumatic irAE within 16 weeks of starting immunotherapy, with median time to onset of 14.5 weeks (table 1). Of the 3 patients with pre-existing AID, 1 experienced a disease flare after starting immunotherapy. <h3>Conclusions</h3> Rheumatic irAEs is a new field that will continue to grow. At this stage we have more questions than answers regarding their epidemiology, natural history and pathophysiology. Our findings reinforce that rheumatic irAEs are complex, at times require aggressive immunosuppression and can impact checkpoint inhibitor therapy for the underlying malignancy. <h3>Disclosure of Interest</h3> C. Calabrese: None declared, E. Kirchner: None declared, A. Kontzias: None declared, V. Velcheti Grant/research support from: Genentech, Bristol-Myers Squibb, Merck, Astra Zeneca, Genoptix, Consultant for: Genentech, Bristol-Myers Squibb, Merck, Astra Zeneca, Celgene, Genoptix, Foundation Medicine, L. Calabrese Consultant for: Bristol-Myers Squibb
Effect of Malaria Initiative
Authors: M.J. Friedrich
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA 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
UK doctor is suspended after certifying taxi drivers without seeing medical records
Authors: Clare Dyer
Journal: BMJ (2017)

An associate specialist in orthopaedics and part time out-of-hours GP has been suspended from the UK medical register for a month after he admitted to certifying 127 taxi drivers as fit to drive a cab without seeing their medical records.

Bimal Singh assessed prospective taxi drivers in Hartlepool and Middlesbrough over a nine month period, a task normally undertaken by the driver’s own GP. On each report, he falsely signed a declaration that he had seen their medical records.

Singh failed to tell his primary or …
Light Therapy Promoting Dopamine Release by Stimulating Retina in Parkinson Disease
Authors: Zhaoming Li, Tian Tian
Journal: JAMA Neurology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Women are reluctant to seek help for perinatal distress, finds UK study
Authors: Susan Mayor
Journal: BMJ (2017)

A fear of being seen as a “bad mother,” failure to recognise or articulate a problem, and a belief that health professionals focus on the health of babies rather than mothers can all dissuade women from seeking help for perinatal psychological distress, a review of UK primary care research studies has found.1

“Psychological distress and problems are common in pregnant women and new months, but very few women access treatment,” said the review authors, led by Suzanne Lee, from the School of Health Sciences at City, University of London (formerly City University). To explore why, the authors analysed 24 qualitative studies on women’s …
ナノトポグラフィーによる異物反応の克服:ナノファイバー膜の生体適合性と免疫隔離特性【Powered by NICT】
Authors: Wang Kai, Hou Wen-Da, Wang Xi, Han Chengsheng, Vuletic Ivan, Su Ni, Zhang Wen-Xi, Ren Qiu-Shi, Chen Liangyi, Luo Ying
Journal: Biomaterials (2016)
Treatment of limited disease small cell lung cancer: the multidisciplinary team
Authors: Markus Glatzer, Achim Rittmeyer, Joachim Müller, Isabelle Opitz, Alexandros Papachristofilou, Ioannis Psallidas, Martin Früh, Diana Born, Paul Martin Putora
Journal: European Respiratory Journal (2017)

Small cell lung cancer (SCLC) presents multiple interdisciplinary challenges with several paradigm shifts in its treatment in recent years. SCLC treatment requires multidisciplinary management and timely treatment. The aim of this review is to focus on the team management aspects in the treatment of limited disease SCLC and how this can contribute towards improving outcomes.
増強されたアップ/ダウンコンバージョンルミネセンスと熱:マルチモーダル画像誘導治療法のための単一コア‐シェル構造における達成同時【Powered by NICT】
Authors: He Fei, Feng Lili, Yang Piaoping, Liu Bin, Gai Shili, Yang Guixin, Dai Yunlu, Lin Jun
Journal: Biomaterials (2016)
Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction
Authors: Sandeep Prabhu, Andrew J. Taylor, Ben T. Costello, David M. Kaye, Alex J.A. McLellan, Aleksandr Voskoboinik, Hariharan Sugumar, Siobhan M. Lockwood, Michael B. Stokes, Bhupesh Pathik, Chrishan J. Nalliah, Geoff R. Wong, Sonia M. Azzopardi, Sarah J. Gutman, Geoffrey Lee, Jamie Layland, Justin A. Mariani, Liang-han Ling, Jonathan M. Kalman, Peter M. Kistler
Journal: Journal of the American College of Cardiology (2017)
Functional Outcome After Intracranial Pressure Monitoring for Children With Severe Traumatic Brain Injury
Authors: Tellen D. Bennett, Peter E. DeWitt, Tom H. Greene, Rajendu Srivastava, Jay Riva-Cambrin, Michael L. Nance, Susan L. Bratton, Desmond K. Runyan, J. Michael Dean, Heather T. Keenan
Journal: JAMA Pediatrics (2017)

Intracranial pressure (ICP) monitoring is a mainstay of therapy for children with traumatic brain injury (TBI), but its overall association with patient outcome is unclear.To test the hypothesis that ICP monitoring is associated with improved functional survival of children with severe TBI.A propensity-weighted effectiveness analysis was conducted using 2 linked national databases with data from 30 US children's hospitals from January 1, 2007, to December 31, 2012, on 3084 children with severe TBI. Clinical events including neurosurgical procedures were identified using validated computable phenotypes. Data analysis was conducted from September 1, 2016, to March 1, 2017.Placement of an ICP monitor.A composite of hospital mortality, discharge to hospice, or survival with placement of new tracheostomy and gastrostomy tubes.Of the 3084 children in the study (1128 girls and 1956 boys; mean [SD] age, 7.03 [5.44] years), 1002 (32.4%) underwent ICP monitoring, with substantial hospital variation (6% to 50% by hospital). Overall, 484 children (15.7%) experienced the primary composite outcome. A propensity approach using matching weights generated good covariate balance between those who did and those who did not undergo ICP monitoring. Using a propensity-weighted logistic regression model clustered by hospital, no statistically significant difference was found in functional survival between monitored and unmonitored patients (odds ratio of poor outcome among those who underwent ICP monitoring, 1.31; 95% CI, 0.99-1.74). In a prespecified secondary analysis, no difference in mortality was found (odds ratio, 1.16; 95% CI, 0.89-1.50). Prespecified subgroup analyses of children younger and older than 2 years of age and among those with unintentional and inflicted (intentional) injuries also showed no difference in outcome with ICP monitoring.With the use of linked national data and validated computable phenotypes, no evidence was found of a benefit from ICP monitoring on functional survival of children with severe TBI. Intracranial pressure monitoring is a widely but inconsistently used technology with incompletely demonstrated effectiveness. A large prospective cohort study or randomized trial is needed.
グローバルDNAメチル化との間の特異的クロストークと未加工および機能化したMWCNTによる細胞型特異的ストレス応答と関連したメタボロミクス【Powered by NICT】
Authors: Chatterjee Nivedita, Yang Jisu, Yoon Dahye, Kim Suhkmann, Joo Sang-Woo, Choi Jinhee
Journal: Biomaterials (2017)
Updated Outcomes of Fludarabine/Melphalan/Bortezomib (Flu/Mel/Vel) Conditioning for Upfront Allogeneic Hematopoietic Cell Transplantation in Multiple Myeloma
Authors: Taiga Nishihori, Claudio Anasetti, Rachid Baz, Jose L Ochoa-Bayona, Kenneth H. Shain, Ryan Hillgruber, Melissa Alsina
Journal: Blood (2016)
Echocardiographic-Derived Strain-Area Loop of the Right Ventricle is Related to Pulmonary Vascular Resistance in Pulmonary Arterial Hypertension
Authors: Hugo G. Hulshof, Arie P. van Dijk, Keith P. George, Daphne Merkus, Kelly Stam, Richard W. van Duin, Koen van Tertholen, Maria T.E. Hopman, François Haddad, Dick H.J. Thijssen, David L. Oxborough
Journal: JACC. Cardiovascular imaging (2017)
Impact of Paradoxical Decrease in High-Density Lipoprotein Cholesterol Levels after Statin Therapy on Major Adverse Cardiovascular Events
Authors: Hirayama Kenshi, Ota Tomoyuki, Harada Kazuhiro, Harata Shingo, Shibata Yohei, Kawashima Kazuhiro, Kunimura Ayako, Takayama Yohei, Shinbo Yusaku, Tatami Yosuke, Kawamiya Toshiki, Yamamoto Dai, Osugi Naohiro, Suzuki Susumu, Ishii Hideki, Murohara Toyoaki
Journal: Circulation (2016)
Abstract 294: Hematopoietic Cells Are Required For Proper Development Of Coronary Vasculature
Authors: Gentian Lluri, Xiaoqian Liu, Atsushi N
Journal: Circulation Research (2013)

Objective: We examined whether the hematopoietic cells induce the coronary artery formation using genetically modified mouse models of hematopoietic ablation in vivo and ex vivo . Methods: As a model of for hematopoietic cell deficient animals, we used Runx1 (a transcription factor required for definitive hematopoiesis) knockout embryos and Vav1-cre; R26-DTA embryos, which ablates 2/3 of CD45+ hematopoietic cells. The coronary growth and the hematopoietic cells were evaluated in whole-mount, section and ex vivo explant culture. Results: The developing coronary endothelial cells form blood-island-like structure at around E12.5 in the subepicardial region. Interestingly, however, the histological analyses suggest that the first Ter119+ and CD45+ blood cells appear in the subendocardial area at E10.5, even before the formation of coronary channels. These initial hematopoietic cells in the heart are not likely derived from the epicardium, as the sorted epicardial cells yielded no hematopoietic cell in colony formation assay. These observations raised a question whether these heart-resident hematopoietic cells rather play an inductive role during coronary formation. To examine this possibility, we analyzed two hematopoietic ablation models. Both Runx1 knockout embryos and Vav1-cre; R26-DTA embryos revealed disorganized, hypoplastic microvasculature of coronary vessels on section and whole-mount stainings. Furthermore, coronary explant experiments showed that the mouse heart explants from Runx1 knockout embryos and Vav1-cre; R26-DTA embryos exhibited impaired coronary formation ex vivo. Conclusion: Hematopoietic cells are not merely transported via coronary vessels, but substantially involved in the induction of the coronary vessels during cardiogenesis.
Adipokines are dysregulated in patients with hidradenitis suppurativa
Authors: A. Malara, R. Hughes, L. Jennings, C.M. Sweeney, M. Lynch, F. Awdeh, I. Timoney, A.M. Tobin, K. Lynam-Loane, L. Tobin, A. Hogan, D. O'Shea, B. Kirby
Journal: British Journal of Dermatology (2017)

Hidradenitis suppurativa (HS), is characterized by the appearance of painful subcutaneous nodules and dermal abscesses in the axillae, perineum and inframammary folds. The development of HS has been linked to factors such as cigarette smoking and obesity1. Patients with HS are more likely to have metabolic syndrome than control populations and develop early cardiovascular diseases2. Adipokines are signalling molecules secreted by adipose tissue and peripheral blood mononuclear cells. The expression of adipokines is dysregulated in obesity and cardiovascular diseases3.

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