tbuckley/cabot-search huggingface dataset:
Improving Disclosure of Financial Conflicts of Interest for Research on Psychosocial Interventions
Authors: Ioana-Alina Cristea, John P. A. Ioannidis
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
In vivo migration of mesenchymal stem cells to burn injury sites and their therapeutic effects in a living mouse model
Authors: Eun Jung Oh, Ho Won Lee, Senthilkumar Kalimuthu, Tae Jung Kim, Hyun Mi Kim, Se Hwan Baek, Liya Zhu, Ji Min Oh, Seung Hyun Son, Ho Yun Chung, Byeong-Cheol Ahn
Journal: Journal of Controlled Release (2018)
Tobacco Smoking-Associated Alterations in the Immune Microenvironment of Squamous Cell Carcinomas
Authors: Alexis Desrichard, Fengshen Kuo, Diego Chowell, Ken-Wing Lee, Nadeem Riaz, Richard J Wong, Timothy A Chan, Luc G T Morris
Journal: JNCI Journal of the National Cancer Institute (2018)

Tobacco smoking creates DNA damage, inducing mutations and potentially altering the tumor immune microenvironment. These types of genetic and immune microenvironment alterations are critical factors known to affect tumor response to immunotherapy. Here we analyze the association between the mutational signature of tobacco smoking, tumor mutational load, and metrics of immune activity in squamous cell carcinomas arising in the head and neck and lung. Using RNA and DNA sequencing data from The Cancer Genome Atlas head and neck (HNSC; n = 287) and lung (LUSC; n = 130) squamous cell carcinoma data sets and two independent gene expression data sets (HNSC, n = 136; LUSC, n = 75), we examined associations between the mutational smoking signature, mutation count, immune cell infiltration, cytolytic activity, and interferon-γ signaling. An increasing mutational smoking signature was associated with statistically significantly increased overall mutational load in both HNSC (ρ = .33, P = 1.01 × 10−7) and LUSC (ρ = .49, P = 2.80 × 10−9). In HNSC, a higher mutational smoking signature was associated with lower levels of immune infiltration (ρ = –.37, P = 1.29 × 10−10), cytolytic activity (ρ = –.28, P = 4.07 × 10−6), and interferon-γ pathway signaling (ρ = .39, P = 3.20 × 10−11). In LUSC, these associations were reversed (ρ = .19, P = .03; ρ = .20, P = .02; and ρ = .18, P = .047, respectively). Differentially expressed genes between smoking-high and smoking-low tumors revealed broad tobacco-induced immunosuppression in HNSC, in contrast to a tumor-inflamed microenvironment in smokers with LUSC. In squamous cell carcinomas, the genetic smoking signature is associated with higher mutational load, but variable effects on tumor immunity can occur, depending on anatomic site. In HNSC, smoking is predominantly immunosuppressive; in LUSC, more pro-inflammatory. Both tumor mutation load and immune microenvironment affect clinical response to immunotherapy. Thus, the mutational smoking signature is likely to have relevance for immunotherapeutic investigation in smoking-associated cancers.
Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden
Authors: Matthew D. Hellmann, Tudor-Eliade Ciuleanu, Adam Pluzanski, Jong Seok Lee, Gregory A. Otterson, Clarisse Audigier-Valette, Elisa Minenza, Helena Linardou, Sjaak Burgers, Pamela Salman, Hossein Borghaei, Suresh S. Ramalingam, Julie Brahmer, Martin Reck, Kenneth J. O’Byrne, William J. Geese, George Green, Han Chang, Joseph Szustakowski, Prabhu Bhagavatheeswaran, Diane Healey, Yali Fu, Faith Nathan, Luis Paz-Ares
Journal: New England Journal of Medicine (2018)

Nivolumab plus ipilimumab showed promising efficacy for the treatment of non–small-cell lung cancer (NSCLC) in a phase 1 trial, and tumor mutational burden has emerged as a potential biomarker of benefit. In this part of an open-label, multipart, phase 3 trial, we examined progression-free survival with nivolumab plus ipilimumab versus chemotherapy among patients with a high tumor mutational burden (≥10 mutations per megabase).
Abstract 3262: De Novo Atrial Fibrillation in Patients with Dual Chamber Pacemakers
Authors: Richard J Keating, Jim W Cheung, Kenneth M Stein, Steven M Markowitz, Sei Iwai, Bindi K Shah, Vivian R Tan, Sandhya Dhruvakumar, David P Dobesh, Dmitry Nemirovsky, Bruce B Lerman, Suneet Mittal
Journal: Circulation (2006)

Background:  Brief atrial high rate episodes (AHREs) of even 5 minutes duration, as detected by pacemaker (PPM) diagnostics, are a reliable surrogate for atrial fibrillation (AF) and potentially identify patients at increased risk for stroke and death. However, the incidence and predictors of  de novo  AF following dual chamber PPM implantation are unknown.   Methods : We retrospectively evaluated 127 patients (71 male; 76 ± 11 years)  without  documented AF who underwent PPM implantation for management of sinus node dysfunction. Information regarding patient demographics, cardiovascular diseases, and medication history was obtained. The cumulative percentage of right ventricular pacing (Cum VP) was determined.   Results : During a mean follow-up of 599 ± 353 days, 33 (26%) patients had an AHRE ≥ 5 minutes. Age, gender, ejection fraction, co-morbid medical conditions, use of medications, and burden of atrial pacing were similar between patients with and without AHREs during the follow-up period. The only significant predictor of an AHRE was ≥ 50% Cum VP (RR 2.2; CI [1.1–4.8]; p = 0.03, Figure). The 1- and 2-year incidence of an AHRE    Conclusions:  Cumulative right ventricular pacing ≥ 50% was the sole significant predictor of  de novo  AF (defined as an AHRE ≥ 5 minutes) in patients with sinus node dysfunction following dual chamber PPM implantation and is associated with a more than two-fold increased risk of AF. The routine use of novel pacing strategies that minimize right ventricular pacing merits prospective investigation as a means of reducing the incidence of  de novo  AF in this population.
Abstract 17166: Hypertrophic Cardiomyopathy - Random Burst-like Transcription of Mutated and Wildtype Alleles as Trigger for Phenotype Development
Authors: Theresia Kraft, Kathrin Kowalski, Judith Montag, Ante Radocaj, Mirza Makul, Pia Ernstberger, Andreas Perrot, Antonio Francino, Francesco Navarro-Lopez, Bernhard Brenner
Journal: Circulation (2016)

Mutations in at least 20 different sarcomeric and some non-sarcomeric proteins have been identified in Hypertrophic Cardiomyopathy (HCM). Generally, development of the HCM phenotype is thought to result from functional effects of the respective mutation. Yet, a common mechanism has not yet been identified.  From our previous work we hypothesized that at least for mutations in the beta-myosin heavy chain (β-MyHC,  MYH7 ) contractile imbalance among individual cardiomyocytes due to cell-to-cell variation in the expression of mutated myosin triggers development of HCM-features like myocyte disarray and fibrosis. Stochastic burst-like transcription of the two  MYH7 -alleles maybe the mechanism leading to this allelic imbalance.  To test this hypothesis we analyzed (i) contractile function of cardiomyocytes of HCM-patients with β-MyHC-mutations Arg723Gly and Ala200Val, (ii) the fraction of mutant  MYH7- mRNA in individual cardiomyocytes isolated from the same patients’ samples, (iii) activity of transcription sites in individual cardiomyocytes by FISH (fluorescence in-situ hybridization), and performed (iv) model simulation of burst-like transcription.  For both mutations, altered calcium-sensitivity with significant cell-to-cell variability was found. This was consistent with  MYH7 -mRNA quantification showing a highly variable fraction of mutated mRNA ranging from cardiomyocytes expressing essentially pure mutant to others with essentially pure wildtype  MYH7 -mRNA. FISH of cardiomyocytes revealed nuclei with no active transcription sites, inconsistent with continuous transcription of  MYH7.  Model simulations of independent burst-like transcription of mutant and wildtype alleles showed large cell-to-cell variability in mutant  MYH7 -mRNA and β-MyHC-protein, just like our cell-by-cell quantifications.  In conclusion, we show that cell-to-cell contractile variability, presumably by variation in mutant mRNA and protein most likely is due to random, independent, burst-like transcription of mutant and wildtype  MYH7- alleles. In HCM-patients, the contractile imbalance over time can induce cardiomyocyte distortions, and lead to fibrosis. HCM-mutations in other sarcomeric proteins could have the same underlying disease mechanism.
ERα-Mediated Nuclear Sequestration of RSK2 Is Required for ER+ Breast Cancer Tumorigenesis
Authors: Katarzyna A. Ludwik, Oliver G. McDonald, David R. Brenin, Deborah A. Lannigan
Journal: Cancer Research (2018)

Although ribosomal protein S6 kinase A3 (RSK2) activation status positively correlates with patient responses to antiestrogen hormonal therapies, the mechanistic basis for these observations is unknown. Using multiple in vitro and in vivo models of estrogen receptor-positive (ER+) breast cancer, we report that ERα sequesters active RSK2 into the nucleus to promote neoplastic transformation and facilitate metastatic tumor growth. RSK2 physically interacted with ERα through its N terminus to activate a proneoplastic transcriptional network critical to the ER+ lineage in the mammary gland, thereby providing a gene signature that effectively stratified patient tumors according to ERα status. ER+ tumor growth was strongly dependent on nuclear RSK2, and transgenic mice engineered to stably express nuclear RSK2 in the mammary gland developed high-grade ductal carcinoma in situ Mammary cells isolated from the transgenic model and introduced systemically successfully disseminated and established metastatic lesions. Antiestrogens disrupted the interaction between RSK2 and ERα, driving RSK2 into the cytoplasm and impairing tumor formation. These findings establish RSK2 as an obligate participant of ERα-mediated transcriptional programs, tumorigenesis, and divergent patient responses to antiestrogen therapies.Significance: Nuclear accumulation of active RSK drives a protumorigenic transcriptional program and renders ER+ breast cancer susceptible to endocrine-based therapies. Cancer Res; 78(8); 2014-25. ©2018 AACR.
Effect of imprime PGG on innate immune-activating pharmacodynamic changes in a phase I clinical study in healthy human volunteers.
Authors: Nandita Bose, Nadine Ottoson, Ben Harrison, Jamie R. Lowe, Mark Matson, Xiaohong Qiu, Adria Bykowski Jonas, Blaine Rathmann, Takashi Kangas, Lindsay R. Wurst, Anissa S.H. Chan, Kathryn Fraser, Richard Walsh, Katie E. Ertelt, Steven Leonardo, Ross Fulton, Keith Gorden, Mark Uhlik, Jeremy Graff, Richard Dale Huhn
Journal: Journal of Clinical Oncology (2017)

33 Background: Imprime PGG (Imprime) is currently in clinical development as combination therapy with checkpoint inhibitors. Imprime, a yeast-derived, soluble β-1,3/1,6 glucan is a Pathogen Associated Molecular Pattern (PAMP) that complexes with endogenous anti-beta glucan antibodies (ABA) and activates innate immune effector cells to trigger the anti-cancer immunity cycle. In this study, we sought to investigate the immunopharmacodynamic (IPD) responses of Imprime in healthy human subjects. Methods: Group 1 (n=12) received a single IV infusion of Imprime 4 mg/kg, Group 2 (n=12) received three weekly infusions of 4mg/kg Imprime. Group 3 (n=12) received infusions of 4 mg/kg or 2 mg/kg Imprime on weeks 1, 2 and 5. In groups 1 and 2, six subjects each received premedication with diphenhydramine 50 mg IV and dexamethasone 8 mg IV. IPD changes were measured at various times before, during and after Imprime administration. Results: Peak levels of complement activation products, C5a and SC5b-9 were detected at the end of infusion (EOI). A 2 to 3-fold increase in neutrophil and monocyte numbers were seen 4 hours post-Imprime infusion. Chemokines, especially IL-8 and MCP-1, were consistently detected at EOI. Cellular analyses showed Imprime binding to neutrophils, monocytes, subsets of DC and B cells. 24 hrs after EOI, a population of intermediate monocytes expressing higher levels of the activation markers CD86, PD-L1, and HLA-DR, was observed. Approximately one week post-Imprime, increased switched memory B cells and plasmablasts were detected. Consistent increase in expression of innate immune activation marker genes was evident as well. A substantial drop in free ABA and a concomitant increase in circulating immune complexes were seen at the EOI. Adverse events (AE) were limited to infusion related reactions. Importantly, the IPD changes and the AE were seen in subjects with higher ABA levels. The effect of pre-medications on some of the IPD will also be presented. Conclusions: These human data provide the first evidence linking pre-treatment ABA levels and Imprime IPD, substantiating the use of these pre-treatment ABA levels for patient selection.
Abstract 14588: Trends, Predictors and Outcomes of Coronary Artery Perforation During Percutaneous Coronary Intervention: Insights From NCDR® Cath PCI Registry
Authors: Ramez Nairooz, Edward McNulty, Amr Mohsen, Craig Parzynski, Jeptha Curtis, Barry Uretsky, Abdul Hakeem
Journal: Circulation (2016)

Introduction: Coronary artery perforation (CAP) is a rare but dreaded complication of percutaneous coronary intervention (PCI). Our aim was to study trends, predictors and outcomes of CAP in the co...
Sequential ALK Inhibitors Can Select for Lorlatinib-Resistant Compound <i>ALK</i> Mutations in ALK-Positive Lung Cancer
Authors: Satoshi Yoda, Jessica J. Lin, Michael S. Lawrence, Benjamin J. Burke, Luc Friboulet, Adam Langenbucher, Leila Dardaei, Kylie Prutisto-Chang, Ibiayi Dagogo-Jack, Sergei Timofeevski, Harper Hubbeling, Justin F. Gainor, Lorin A. Ferris, Amanda K. Riley, Krystina E. Kattermann, Daria Timonina, Rebecca S. Heist, A. John Iafrate, Cyril H. Benes, Jochen K. Lennerz, Mari Mino-Kenudson, Jeffrey A. Engelman, Ted W. Johnson, Aaron N. Hata, Alice T. Shaw
Journal: Cancer Discovery (2018)

Abstract The cornerstone of treatment for advanced ALK-positive lung cancer is sequential therapy with increasingly potent and selective ALK inhibitors. The third-generation ALK inhibitor lorlatinib has demonstrated clinical activity in patients who failed previous ALK inhibitors. To define the spectrum of ALK mutations that confer lorlatinib resistance, we performed accelerated mutagenesis screening of Ba/F3 cells expressing EML4–ALK. Under comparable conditions, N-ethyl-N-nitrosourea (ENU) mutagenesis generated numerous crizotinib-resistant but no lorlatinib-resistant clones harboring single ALK mutations. In similar screens with EML4–ALK containing single ALK resistance mutations, numerous lorlatinib-resistant clones emerged harboring compound ALK mutations. To determine the clinical relevance of these mutations, we analyzed repeat biopsies from lorlatinib-resistant patients. Seven of 20 samples (35%) harbored compound ALK mutations, including two identified in the ENU screen. Whole-exome sequencing in three cases confirmed the stepwise accumulation of ALK mutations during sequential treatment. These results suggest that sequential ALK inhibitors can foster the emergence of compound ALK mutations, identification of which is critical to informing drug design and developing effective therapeutic strategies. Significance: Treatment with sequential first-, second-, and third-generation ALK inhibitors can select for compound ALK mutations that confer high-level resistance to ALK-targeted therapies. A more efficacious long-term strategy may be up-front treatment with a third-generation ALK inhibitor to prevent the emergence of on-target resistance. Cancer Discov; 8(6); 714–29. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 663
Catalyzing Future Drug, Device, and Information Technology Breakthroughs in Dermatology
Authors: Shuai Xu, Jamie Breslin, William Ju
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Pervasive mutations of JAK-STAT pathway genes in classical Hodgkin lymphoma
Authors: Enrico Tiacci, Erik Ladewig, Gianluca Schiavoni, Alex Penson, Elisabetta Fortini, Valentina Pettirossi, Yuchun Wang, Ariele Rosseto, Alessandra Venanzi, Sofija Vlasevska, Roberta Pacini, Simonetta Piattoni, Alessia Tabarrini, Alessandra Pucciarini, Barbara Bigerna, Alessia Santi, Alessandro M. Gianni, Simonetta Viviani, Antonello Cabras, Stefano Ascani, Barbara Crescenzi, Cristina Mecucci, Laura Pasqualucci, Raul Rabadan, Brunangelo Falini
Journal: Blood (2018)
Crizotinib in patients with advanced, inoperable inflammatory myofibroblastic tumours with and without anaplastic lymphoma kinase gene alterations (European Organisation for Research and Treatment of Cancer 90101 CREATE): a multicentre, single-drug, prospective, non-randomised phase 2 trial
Authors: Patrick Schöffski, Jozef Sufliarsky, Hans Gelderblom, Jean-Yves Blay, Sandra J Strauss, Silvia Stacchiotti, Piotr Rutkowski, Lars H Lindner, Michael G Leahy, Antoine Italiano, Nicolas Isambert, Maria Debiec-Rychter, Raf Sciot, Thomas Van Cann, Sandrine Marréaud, Axelle Nzokirantevye, Sandra Collette, Agnieszka Wozniak
Journal: The Lancet Respiratory Medicine (2018)
Lyme disease: summary of NICE guidance
Authors: Maria Cruickshank, Norma O’Flynn, Saul N Faust
Journal: BMJ (2018)

### What you need to know Lyme disease is caused by a specific group of Borrelia burgdorferi bacteria, which can be transmitted to humans through a bite from an infected tick. This can result in a number of clinical problems ranging from skin rash to serious involvement of organ systems, including arthritis, and neurological problems. People with skin and non-specific symptoms most commonly present to their general practitioner and are often treated in primary care, whereas people with symptoms affecting organ systems are commonly referred to specialists. The guideline focuses on diagnosis and management of Lyme disease according to clinical presentation and symptoms rather than using the differing classifications of Lyme disease, which are poorly defined and contested. There is a lack of good quality evidence on the epidemiology, prevalence, diagnosis, and management of Lyme disease. This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE).1 ### What's new in this guidance
Low-dose computed tomography for the diagnosis of pneumonia in elderly patients: a prospective, interventional cohort study
Authors: Virginie Prendki, Max Scheffler, Benedikt Huttner, Nicolas Garin, François Herrmann, Jean-Paul Janssens, Christophe Marti, Sebastian Carballo, Xavier Roux, Christine Serratrice, Jacques Serratrice, Thomas Agoritsas, Christoph D. Becker, Laurent Kaiser, Sarah Rosset-Zufferey, Valérie Soulier, Arnaud Perrier, Jean-Luc Reny, Xavier Montet, Jérôme Stirnemann
Journal: European Respiratory Journal (2018)

The diagnosis of pneumonia is challenging. Our objective was to assess whether low-dose computed tomography (LDCT) modified the probability of diagnosing pneumonia in elderly patients. We prospectively included patients aged over 65 years with a suspicion of pneumonia treated with antimicrobial therapy (AT). All patients had a chest radiograph and LDCT within 72 h of inclusion. The treating clinician assessed the probability of pneumonia before and after the LDCT scan using a Likert scale. An adjudication committee retrospectively rated the probability of pneumonia and was considered as the reference for diagnosis. The main outcome was the difference in the clinician's pneumonia probability estimates before and after LDCT and the proportion of modified diagnoses which matched the reference diagnosis (the net reclassification improvement (NRI)). A total of 200 patients with a median age of 84 years were included. After LDCT, the estimated probability of pneumonia changed in 90 patients (45%), of which 60 (30%) were downgraded and 30 (15%) were upgraded. The NRI was 8% (NRI event (−6%) + NRI non-event (14%)). LDCT modified the estimated probability of pneumonia in a substantial proportion of patients. It mostly helped to exclude a diagnosis of pneumonia and hence to reduce unnecessary AT.
Cliff Roberton: devoted his working life to improving the care of babies
Authors: Robert Whitaker, Nick Barnes, Colin Morley
Journal: BMJ (2018)

Clifford Roberton (“Cliff”) was a distinguished member of the first generation of neonatal paediatricians who developed and promoted the science and practice of the medical care of ill newborn babies. His talent was the synthesis and organisation of medical knowledge within his specialty.

Cliff was born and brought up in Oswaldtwistle, Lancashire, and attended school in Accrington before reading medicine at Downing College, Cambridge, and then at University College Hospital, London, where he won three scholarships and came top in his year. He did his house jobs at UCH and then trained in neonatal medicine, first as a research fellow and registrar in paediatrics at the Hammersmith Hospital under the guidance of Peter Tizard, and then at the Nuffield Institute for Medical Research in Oxford. He was a clinical reader in paediatrics at the University of Oxford before being appointed consultant neonatologist at Addenbrooke’s Hospital, Cambridge, and associate lecturer …
138PD_PR Patient-reported outcomes (PROs) in ALEX: A phase III study of alectinib (ALEC) vs crizotinib (CRIZ) in non-small-cell lung cancer (NSCLC)
Authors: M. Perol, S. Peters, N. Pavlakis, E. Levchenko, M. Platania, J. Oliveira, S. Novello, T. Karagiannis, A. Zeaiter, R. Dziadziuszko
Journal: Journal of Thoracic Oncology (2018)
67P The influence of circulating tumor DNA analysis on response to immunotherapy in non-small cell lung cancer (NSCLC)
Authors: R. Grinberg, L.C. Roisman, S. Geva, L. Soussan-Gutman, A. Dvir, R. Yair, T. Twito, R. Larman, N. Peled
Journal: Journal of Thoracic Oncology (2018)