tbuckley/cabot-search huggingface dataset:
THU0007 Deep sequencing transcriptome analysis of the effect of traumeel versus diclofenac therapeutic action in wound healing
Authors: GSt Laurent, B Seilheimer, M Tackett, J Zhou, D Shtokalo, Y Vyatkin, P Kapranov, I Toma, T Mccaffrey
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Anti-inflammatory agents are used widely in treating numerous inflammatory conditions. The effect of Tr14, a multitargeted natural product, was compared to diclofenac, a non-selective cyclooxygenase inhibitor, on cutaneous wound repair in mice. <h3>Objectives</h3> To compare the effect of diclofenac with Tr14 on the transcriptome after cutaneous wounding in the mouse. <h3>Methods</h3> After abrasive wounding, the wounds were treated with topical Tr14 or diclofenac at clinically relevant doses. An additional group received subcutaneous Tr14 injections. The healing wounds were analyzed for RNA transcript profiling by RNAseq at specific times (12h, 24h, 36h, 72h, 96h, 120h, 196h) after injury. Differentially expressed genes (DEGs) were computed at each time point between diclofenac vs control or Tr14 vs control using EdgeR. <h3>Results</h3> Across time points, Tr14 treatment modulated a number of transcripts related to key wound repair pathways such as cellular differentiation, wound contraction, and cell mobility. Diclofenac, in contrast, changed gene expression mainly in two areas: Prominent effects were observed with regard to DNA chromatin regulation and ribosomal function, further effects were observed on the prostaglandin pathway and wound repair factors. In many of the key pathways modulated by Tr14, such as the defense response and cell motility, diclofenac tended to have an opposite effect on gene expression. At 12 hours post-injury, there were 521 transcripts significantly elevated and 1027 transcripts that were decreased by diclofenac treatment. By comparison, using a similar number of transcripts altered by Tr14 treatment, only 4 transcripts were increased in common, and 5 transcripts were decreased in common, suggesting that the therapies have different effects on the transcriptome. <h3>Conclusions</h3> The overall patterns of the Tr14 and diclofenac responses in the transcriptome during wound repair are very different. The Tr14 effect is most pronounced on the defense response, cell motility, and anti-apoptotic pathways. In contrast, diclofenac mainly affected histones and chromatin remodeling systems, as well as ribosomal systems that would be expected to alter the translational pattern of diclofenac-treated cells. <h3>Disclosure of Interest</h3> G. St. Laurent, III: None declared, B. Seilheimer: None declared, M. Tackett: None declared, J. Zhou: None declared, D. Shtokalo: None declared, Y. Vyatkin: None declared, P. Kapranov: None declared, I. Toma: None declared, T. Mccaffrey Speakers bureau: TM has received speaker9s honorarium from HEEL, GmbH
神経炎症のデンドリマを媒体とする標的化におけるナノスケール効果【Powered by NICT】
Authors: Nance Elizabeth, Zhang Fan, K Mishra Manoj, Zhang Zhi, P Kambhampati Siva, M Kannan Rangaramanujam, Kannan Sujatha
Journal: Biomaterials (2016)
Abstract 13965: Aerobic Exercise After an ICD: Results of the Psychological and Quality of Life Outcomes in the Anti-Arrhythmic Effects of Exercise After an ICD Trial
Authors: Cynthia M Dougherty, Robb L Glenny, Peter J Kudenchuk, Robert L Burr
Journal: Circulation (2016)

Introduction: The Anti-Arrhythmic Effects of Exercise Trial reported aerobic exercise training for 8-24 weeks after an implantable cardioverter defibrillator (ICD) significantly improved cardiopulmonary function. The purpose of this report is to outline the 8 and 24 week quality of life and psychological outcomes of the trial. Methods: 160 subjects with a prior ICD implant (40% primary and 60% secondary prevention), mean age 55 ±12 years, 77.5% male, 84% Caucasian, 100% beta-blocked, and EF%=40%, entered a RCT comparing aerobic exercise (EX) to usual care (UC). EX= aerobic training x 8 weeks of home walking 1 hour/day on 5 days/week at 60-80% of maximum HR, followed by aerobic maintenance x 16 weeks of home walking for 150 min/week. At baseline, 8 and 24 weeks, participants completed questionnaires: Quality of Life (SF-36), Anxiety (State-Trait Anxiety Inventory), Depression (PHQ-9), and Symptoms (Patient Concerns Assessment). Adherence to exercise was tracked with Polar HR monitors and pedometers. Analysis of variance was used to determine group x time effects on study outcomes and by adherence groups. Results: There were no differences noted between EX and UC on quality of life, symptoms, or anxiety at 8 or 24 weeks using intent-to-treat. There was a significant reduction in depression severity between EX vs UC at 8 weeks (p=0.05). When comparing those who exercised at ≥80% (N=48) to &lt;80% (N=36) and UC (N=76), there were statistically significant improvements in quality of life [positive health transition, (p=0.006) and social function (p=0.03)], with a reduction in fear of dying (p=0.04), anxiety (p=0.02), and depression severity (p=0.04) at 8 weeks in those who exercise at ≥80%. Those who continued to exercise at ≥80% for 16 more weeks, had a significant continued improvement in quality of life [positive health transitions (p=0.006), physical function (p=0.01), vitality (p=0.04), social function (p=0.03), and role emotional (p=0.02)], while anxiety (p=0.002) and symptoms (p=0.003) were reduced. Depression by adherence groups at 24 weeks was unchanged. Conclusions: Aerobic exercise training and maintenance for those who actually exercised as prescribed, had benefits in improved quality of life, with reductions in symptoms and psychological distress.
Intra-Aortic Balloon Pump Optimizes Myocardial Function During Cardiogenic Shock
Authors: Thomas Dahlslett, Sigve Karlsen, Bjørnar Grenne, Benthe Sjøli, Bjørn Bendz, Helge Skulstad, Otto A. Smiseth, Thor Edvardsen, Harald Brunvand
Journal: JACC. Cardiovascular imaging (2017)
Synergy of WEE1 and mTOR Inhibition in Mutant <i>KRAS</i>-Driven Lung Cancers
Authors: Josephine Hai, Shengwu Liu, Lauren Bufe, Khanh Do, Ting Chen, Xiaoen Wang, Christine Ng, Shuai Li, Ming-Sound Tsao, Geoffrey I. Shapiro, Kwok-Kin Wong
Journal: Clinical Cancer Research (2017)

Purpose:KRAS-activating mutations are the most common oncogenic driver in non-small cell lung cancer (NSCLC), but efforts to directly target mutant KRAS have proved a formidable challenge. Therefore, multitargeted therapy may offer a plausible strategy to effectively treat KRAS-driven NSCLCs. Here, we evaluate the efficacy and mechanistic rationale for combining mTOR and WEE1 inhibition as a potential therapy for lung cancers harboring KRAS mutations.Experimental Design: We investigated the synergistic effect of combining mTOR and WEE1 inhibitors on cell viability, apoptosis, and DNA damage repair response using a panel of human KRAS-mutant and wild type NSCLC cell lines and patient-derived xenograft cell lines. Murine autochthonous and human transplant models were used to test the therapeutic efficacy and pharmacodynamic effects of dual treatment.Results: We demonstrate that combined inhibition of mTOR and WEE1 induced potent synergistic cytotoxic effects selectively in KRAS-mutant NSCLC cell lines, delayed human tumor xenograft growth and caused tumor regression in a murine lung adenocarcinoma model. Mechanistically, we show that inhibition of mTOR potentiates WEE1 inhibition by abrogating compensatory activation of DNA repair, exacerbating DNA damage in KRAS-mutant NSCLC, and that this effect is due in part to reduction in cyclin D1.Conclusions: These findings demonstrate that compromised DNA repair underlies the observed potent synergy of WEE1 and mTOR inhibition and support clinical evaluation of this dual therapy for patients with KRAS-mutant lung cancers. Clin Cancer Res; 23(22); 6993-7005. ©2017 AACR.
脂質代謝と心血管保護におけるCTRP3とCTRP9の簡単な展望【Powered by NICT】
Authors: Yang Yang, Li Yue, Ma Zhiqiang, Jiang Shuai, Fan Chongxi, Hu Wei, Wang Dongjin, Di Shouyin, Sun Yang, Yi Wei
Journal: Progress in Lipid Research (2016)
Reconnection to mechanical ventilation for 1 h after a successful spontaneous breathing trial reduces reintubation in critically ill patients: a multicenter randomized controlled trial
Authors: M. Mar Fernandez, Alejandro González-Castro, Monica Magret, M. Teresa Bouza, Marcos Ibañez, Carolina García, Begoña Balerdi, Arantxa Mas, Vanesa Arauzo, José M. Añón, Francisco Ruiz, José Ferreres, Roser Tomás, Marta Alabert, Ana Isabel Tizón, Susana Altaba, Noemi Llamas, Rafael Fernandez
Journal: Intensive Care Medicine (2017)
ペプチド金ナノ粒子ハイブリッドによるエンドソームpH変調は食作用性免疫細胞における強力な抗炎症活性を可能にする【Powered by NICT】
Authors: Yang Hong, Kozicky Lisa, Saferali Aabida, Fung Shan-Yu, Afacan Nicole, Cai Bing, Falsafi Reza, Gill Erin, Liu Mingyao, R Kollmann Tobias, Hancock R.E.W., M Sly Laura, E Turvey Stuart
Journal: Biomaterials (2016)
Selected Alkylating Agents Can Overcome Drug Tolerance of G0-like Tumor Cells and Eradicate BRCA1-Deficient Mammary Tumors in Mice
Authors: Marina Pajic, Sohvi Blatter, Charlotte Guyader, Maaike Gonggrijp, Ariena Kersbergen, Aslι Küçükosmanoğlu, Wendy Sol, Rinske Drost, Jos Jonkers, Piet Borst, Sven Rottenberg
Journal: Clinical Cancer Research (2017)

Purpose: We aimed to characterize and target drug-tolerant BRCA1-deficient tumor cells that cause residual disease and subsequent tumor relapse.Experimental Design: We studied responses to various mono- and bifunctional alkylating agents in a genetically engineered mouse model for BRCA1/p53-mutant breast cancer. Because of the large intragenic deletion of the Brca1 gene, no restoration of BRCA1 function is possible, and therefore, no BRCA1-dependent acquired resistance occurs. To characterize the cell-cycle stage from which Brca1-/-;p53-/- mammary tumors arise after cisplatin treatment, we introduced the fluorescent ubiquitination-based cell-cycle indicator (FUCCI) construct into the tumor cells.Results: Despite repeated sensitivity to the MTD of platinum drugs, the Brca1-mutated mammary tumors are not eradicated, not even by a frequent dosing schedule. We show that relapse comes from single-nucleated cells delaying entry into the S-phase. Such slowly cycling cells, which are present within the drug-naïve tumors, are enriched in tumor remnants. Using the FUCCI construct, we identified nonfluorescent G0-like cells as the population most tolerant to platinum drugs. Intriguingly, these cells are more sensitive to the DNA-crosslinking agent nimustine, resulting in an increased number of multinucleated cells that lack clonogenicity. This is consistent with our in vivo finding that the nimustine MTD, among several alkylating agents, is the most effective in eradicating Brca1-mutated mouse mammary tumors.Conclusions: Our data show that targeting G0-like cells is crucial for the eradication of BRCA1/p53-deficient tumor cells. This can be achieved with selected alkylating agents such as nimustine. Clin Cancer Res; 23(22); 7020-33. ©2017 AACR.
Treatment-Free Remission Accomplished By Dasatinib (TRAD): Preliminary Results of the Pan-Canadian Tyrosine Kinase Inhibitor Discontinuation Trial
Authors: Dennis Dong Hwan Kim, Isabelle Bence-Bruckler, Donna L. Forrest, Mary Lynn Savoie, Stephen Couban, Lambert Busque, Robert Delage, Pierre Laneuville, Elena Liew, Anargyros Xenocostas, Kristjan Paulson, Suzanne Kamel-Reid, Jeff H. Lipton, Brian Leber
Journal: Blood (2016)
Delineation of the timing of second-line therapy post–autologous stem cell transplant in patients with AL amyloidosis
Authors: Yi L. Hwa, Rahma Warsame, Morie A. Gertz, Francis K. Buadi, Martha Q. Lacy, Shaji K. Kumar, David Dingli, Steve R. Zeldenrust, Nelson Leung, Susanne R. Hayman, Prashant Kapoor, Wilson I. Gonsalves, Taxiarchis V. Kourelis, Stephen Russell, Ronald S. Go, Miriam A. Hobbs, Amie L. Fonder, S. Vincent Rajkumar, Angela Dispenzieri
Journal: Blood (2017)
整列したナノ繊維コラーゲン足場‐後天性リンパ浮腫治療のためのリンパ管形成の誘導【Powered by NICT】
Authors: Hadamitzky Catarina, S Zaitseva Tatiana, Bazalova-Carter Magdalena, V Paukshto Michael, Hou Luqia, Strassberg Zachary, Ferguson James, Matsuura Yuka, Dash Rajesh, C Yang Phillip, Kretchetov Shura, M Vogt Peter, G Rockson Stanley, P Cooke John, F Huang Ngan
Journal: Biomaterials (2016)
Atrial Electroanatomic Remodeling After Circumferential Radiofrequency Pulmonary Vein Ablation
Authors: Carlo Pappone, Giuseppe Oreto, Salvatore Rosanio, Gabriele Vicedomini, Monica Tocchi, Filippo Gugliotta, Adriano Salvati, Cosimo Dicandia, Maria Pia Calabrò, Patrizio Mazzone, Eleonora Ficarra, Claudio Di Gioia, Simone Gulletta, Stefano Nardi, Vincenzo Santinelli, Stefano Benussi, Ottavio Alfieri
Journal: Circulation (2001)

Circumferential radiofrequency ablation around pulmonary vein (PV) ostia has recently been described as a new anatomic approach for atrial fibrillation (AF).We treated 251 consecutive patients with paroxysmal (n=179) or permanent (n=72) AF. Circular PV lesions were deployed transseptally during sinus rhythm (n=124) or AF (n=127) using 3D electroanatomic guidance. Procedures lasted 148+/-26 minutes. Among 980 lesions surrounding individual PVs (n=956) or 2 ipsilateral veins with close openings or common ostium (n=24), 75% were defined as complete by a bipolar electrogram amplitude <0.1 mV inside the lesion and a delay >30 ms across the line. The amount of low-voltage encircled area was 3594+/-449 mm(2), which accounted for 23+/-9% of the total left atrial (LA) map surface. Major complications (cardiac tamponade) occurred in 2 patients (0.8%). No PV stenoses were detected by transesophageal echocardiography. After 10.4+/-4.5 months, 152 patients with paroxysmal AF (85%) and 49 with permanent AF (68%) were AF-free. Patients with and without AF recurrence did not differ in age, AF duration, prevalence of heart disease, or ejection fraction, but the LA diameter was significantly higher (P<0.001) in permanent AF patients with recurrence. The proportion of PVs with complete lesions was similar between patients with and without recurrence, but the latter had larger low-voltage encircled areas after radiofrequency (expressed as percent of LA surface area; P<0.001).Circumferential PV ablation is a safe and effective treatment for AF. Its success is likely due to both PV trigger isolation and electroanatomic remodeling of the area encompassing the PV ostia.
The function of normal and mutated epidermal growth facor receptors in glioblastoma multiforme: Establishment of an in vivo and in vitro model
Authors: Marie-Therese Stockhausen, Mette Villingshoj, Mogens Spang-Thomsen, Helle Broholm, Michael Kosteljanetz, Hans Skovgaard Poulsen
Journal: Cancer Research (2007)

3887   Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults with an average incidence of 2-3 new cases per 100.000 in a population each year. GBM is a very heterogeneous tumor, though some molecular changes are characteristic for the disease. Among the most common are amplification or over expression of the Epidermal Growth Factor Receptor (EGFR), a receptor tyrosine kinase involved in proliferation, migration and tumor growth; mutation or deletion of PTEN, a crucial regulator of the PI3-k/Akt pathway important for survival and resistance to apoptosis; as well as over expression of several growth factors such as EGF, TGFα and VEGF. In addition, some GBMs express the tumor specific variant EGFRvIII which lacks part of the extracellular, ligand binding domain of the wild-type EGFR and which shows constitutive activation. The mutated receptor has been implicated in  in vitro  experiments and in animal models to confer an extra growth promoting and tumorigenic effect to the cells. On a macroscopic level, histopathological  extensive areas of necrosis surrounded by pseudopalisading cells and excessive angiogenesis characterize GBMs. Despite multimodal therapy it is still not possible to cure patients with GBM, and the median survival after diagnosis is around 14 months. Due to its heterogenic nature it has long been postulated that individualized treatment is the best way to cure GBM patients and thus it is of great importance to study molecular mechanisms behind the disease, and to develop screening methods by which it will be possible to select patients for specific treatments.  Up to date there are no satisfactory  in vitro  models representing GBM, since EGFR amplification and over expression as well as expression of the tumor specific EGFR mutant EGFRvIII exclusively seem to be  in vivo  phenomenon. In order to establish a good model for GBM both  in vivo  and  in vitro  we have subcutaneously xenografted GBM tissue from patients diagnosed with GBM according to WHO 2000 guidelines onto the flanks of nude mice. The tumors have been serially passaged onto new mice when reaching the maximal ethical size. After each passage, the tumors have been diagnosed as GBM and the expression of EGFR, EGFRvIII and p53 has been investigated by IHC and Western blotting. When established on mice the tumors have been dissected out and allowed to grow  in vitro . This model enables us to test new treatment modalities both  in vitro  and  in vivo  as well as to investigate the underlying mechanisms behind the disease. Data regarding the frequency of EGFR over expression and EGFRvIII expression as well as establishment of GBM cell lines will be presented at the meeting.
A safety evaluation study of STAT-3 Decoy (NSC-741763) in cynomolgus monkeys
Authors: Patricia Tosca, Christa Zwayer, Michael Ryan, Katherine Knostman, Jerry Johnson, Patricia Giclas, Jennifer Grandis, Anthony Welch, James Peggins, Joseph Tomaszewski
Journal: Cancer Research (2008)

2222   STATs (Signal Transducers and Activators of Transcription) are  intracellular signaling proteins that are activated upon tyrosine  phosphorylation and translocate from the cytosol to the nucleus where  they bind to specific regions of DNA and exert transcriptional activity.  STAT-3 activation has been linked to transformation and tumor  progression in several types of cancers including Squamous Cell  Carcinoma of the Head and Neck (SCCHN). NSC-741673, a double  stranded oligonucleotide, is proposed for use in treating SCCHN via  intratumoral administration. This study was conducted to provide  the toxicity data required to support a Phase 0 clinical trial and to  determine whether the STAT-3 activation was modulated (data not  presented). Three study groups (two monkeys/sex/group) were  administered (intramuscularly) vehicle or STAT-3 Decoy on  Day 1, necropsies were performed on Days 2 and 15 (1  monkey/sex/group/day). Dosages were 0, 0.8, and 3.2 mg/kg with a  dose volume of 0.9 mL (flat dose). Upon observation the treated  animals exhibited behavior that was consistent with the vehicle control  group animals. Individual animal body weight values remained within  1% of prestudy weights throughout the study. Increased reticulocyts  and decreased red blood cells, hematocrit, and hemoglobin were seen  throughout the study in all groups. These changes were not dose related  and were attributed to the extensive blood collections throughout the  study. Clinical chemistry fluctuations were considered normal and were  not attributed to the test article. Based on the Bb (Complement  activation breakdown product) levels, there was no activation of the  alternative pathway of complement in any animal at any dose level. All  Bb levels were within the normal range (0.17 -1.09 µg/mL). At  necropsy, there were no gross findings attributed to STAT-3 Decoy.  There were no microscopic findings with an exposure-related incidence  in the routine sections. Based on these findings, the no-observable-  adverse-effect-level (NOAEL) was greater than 3.2 mg/kg when  administered as a single dose to male and female Cynomolgus monkeys.  The maximum dose proposed for the Phase 0 trial is 1.0 mg.  (supported by N01-CM42200 under the NCI RAID Program).
Natural-Killer-like B Cells Display the Phenotypic and Functional Characteristics of Conventional B Cells
Authors: Yann M. Kerdiles, Francisca F. Almeida, Thornton Thompson, Michael Chopin, Margaux Vienne, Pierre Bruhns, Nicholas D. Huntington, David H. Raulet, Stephen L. Nutt, Gabrielle T. Belz, Eric Vivier
Journal: Immunity (2017)
Using Disease Epidemiology to Optimize Immunization Schedules
Authors: Cindy M. Weinbaum, Walter A. Orenstein
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Patients being put at risk from unfilled out-of-hours shifts, GPs warn
Authors: Gareth Iacobucci
Journal: BMJ (2017)

Providers of out-of-hours GP services in England have warned that the rising cost of indemnity cover has left them struggling to fill shifts and is putting the care of patients at risk.

GP indemnity costs have soared in recent years, with doctors who work out of hours being particularly affected. The Department of Health admitted last month that indemnity costs could rise even further after the decision of the Ministry of Justice to lower the personal injury discount rate for claimants1 and is locked in talks with the BMA on how to mitigate the decision’s effect on GPs.

Urgent Health UK, a federation of 23 social enterprises that provide GP out-of-hours services to a population of more than 20 million, has reported …
Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation
Authors: Christopher P. Cannon, Deepak L. Bhatt, Jonas Oldgren, Gregory Y.H. Lip, Stephen G. Ellis, Takeshi Kimura, Michael Maeng, Bela Merkely, Uwe Zeymer, Savion Gropper, Matias Nordaby, Eva Kleine, Ruth Harper, Jenny Manassie, James L. Januzzi, Jurrien M. ten Berg, P. Gabriel Steg, Stefan H. Hohnloser
Journal: New England Journal of Medicine (2017)

Triple antithrombotic therapy with warfarin plus two antiplatelet agents is the standard of care after percutaneous coronary intervention (PCI) for patients with atrial fibrillation, but this therapy is associated with a high risk of bleeding.