tbuckley/cabot-search huggingface dataset:
Long-term disease control of advanced gastrointestinal stromal tumors (GIST) with imatinib (IM): 10-year outcomes from SWOG phase III intergroup trial S0033.
Authors: George D. Demetri, Cathryn J Rankin, Robert S. Benjamin, Ernest C. Borden, Christopher W. Ryan, Dennis A. Priebat, William D. Tap, Margaret von Mehren, Martin E. Blackstein, Michael C. Heinrich, Robert G. Maki, Christopher L. Corless, Jonathan A. Fletcher, Kouros Owzar, Charles David Blanke
Journal: Journal of Clinical Oncology (2014)

10508 Background: S0033 was designed to study the impact of IM, randomized between two doses, in patients (pts) with incurable GIST. Methods: Full accrual to this phase III trial occurred over 8 months, ending 01SEP2001. A study amendment allowed collection of additional clinical information on long-term survival outcomes and annotation of any therapies subsequent to IM. Results: Of 695 eligible patients, 180 (26%) survived 8 years or longer [94 on IM 400 mg/day arm and 86 on IM 800 mg/d arm). The 10-year estimate of overall survival (OS) across both study arms combined is 22% (95% confidence interval (CI)=19-26%). Additional therapy information was obtained for 137 long-term survivors: IM was the sole therapy, administered continuously, in 49%; fifty-four (39%) received subsequent systemic agents, including sunitinib (41) and sorafenib (16). Local therapies, includingsurgical resection of metastases, radiofrequency ablation, and radiation therapy were also utilized in subsets. Univariate analyses with long-term survival data show that pts whose tumors harbored a KIT exon 9 mutation had a significantly shorter OS than those with KIT exon 11 mutations (p=0.0013) or KIT/PDGFRAwild-type (WT) genotypes (0.047). Conclusions: A significant subset of pts with metastatic GIST achieved durable long-term overall survival with single-agent IM. Further investigation of what enables pts to live progression-free for more than a decade is warranted to optimize treatment approaches in this oncogene-driven disease, as well as to improve outcomes for more challenging molecular subsets, including KIT exon 9 or SDH-deficient (KIT/PDGFRA WT) GIST. Clinical trial information: NCT00009906.
Influence of Limited Application of Methylcholanthrene Upon Epidermal Iron and Ascorbic Acid&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: Christopher Carruthers, V. Suntzeff
Journal: JNCI Journal of the National Cancer Institute (1942)

Journal Article Influence of Limited Application of Methylcholanthrene Upon Epidermal Iron and Ascorbic Acid Get access Christopher Carruthers, Christopher Carruthers research associate Search for other works by this author on: Oxford Academic PubMed Google Scholar V. Suntzeff V. Suntzeff research associate Barnard Free Skin and Cancer Hospital, St. Louis Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 3, Issue 2, October 1942, Pages 217–220, https://doi.org/10.1093/jnci/3.2.217 Published: 01 October 1942
A New Promoter Allows Optogenetic Vision Restoration with Enhanced Sensitivity in Macaque Retina
Authors: Antoine Chaffiol, Romain Caplette, Céline Jaillard, Elena Brazhnikova, Mélissa Desrosiers, Elisabeth Dubus, Laëtitia Duhamel, Emilie Macé, Olivier Marre, Patrick Benoit, Philippe Hantraye, Alexis-Pierre Bemelmans, Ernst Bamberg, Jens Duebel, José-Alain Sahel, Serge Picaud, Deniz Dalkara
Journal: Molecular Therapy (2017)

The majority of inherited retinal degenerations converge on the phenotype of photoreceptor cell death. Second- and third-order neurons are spared in these diseases, making it possible to restore retinal light responses using optogenetics. Viral expression of channelrhodopsin in the third-order neurons under ubiquitous promoters was previously shown to restore visual function, albeit at light intensities above illumination safety thresholds. Here, we report (to our knowledge, for the first time) activation of macaque retinas, up to 6 months post-injection, using channelrhodopsin-Ca2+-permeable channelrhodopsin (CatCh) at safe light intensities. High-level CatCh expression was achieved due to a new promoter based on the regulatory region of the gamma-synuclein gene (SNCG) allowing strong expression in ganglion cells across species. Our promoter, in combination with clinically proven adeno-associated virus 2 (AAV2), provides CatCh expression in peri-foveolar ganglion cells responding robustly to light under the illumination safety thresholds for the human eye. On the contrary, the threshold of activation and the proportion of unresponsive cells were much higher when a ubiquitous promoter (cytomegalovirus [CMV]) was used to express CatCh. The results of our study suggest that the inclusion of optimized promoters is key in the path to clinical translation of optogenetics.
Evolution of Surgical Aortic Valve Replacement in the Era of Transcatheter Valve Technology
Authors: Aditya Mantha, Yen-Yi Juo, Ravi Morchi, Ramin Ebrahimi, Boback Ziaeian, Richard J. Shemin, Peyman Benharash
Journal: JAMA Surgery (2017)

Author(s): Mantha, Aditya; Juo, Yen-Yi; Morchi, Ravi; Ebrahimi, Ramin; Ziaeian, Boback; Shemin, Richard J; Benharash, Peyman
Targeting NEK2 attenuates glioblastoma growth and radioresistance by destabilizing histone methyltransferase EZH2
Authors: Jia Wang, Peng Cheng, Marat S. Pavlyukov, Hai Yu, Zhuo Zhang, Sung-Hak Kim, Mutsuko Minata, Ahmed Mohyeldin, Wanfu Xie, Dongquan Chen, Violaine Goidts, Brendan Frett, Wenhao Hu, Hongyu Li, Yong Jae Shin, Yeri Lee, Do-Hyun Nam, Harley I. Kornblum, Maode Wang, Ichiro Nakano
Journal: Journal of Clinical Investigation (2017)

Accumulating evidence suggests that glioma stem cells (GSCs) are important therapeutic targets in glioblastoma (GBM). In this study, we identified NIMA-related kinase 2 (NEK2) as a functional binding protein of enhancer of zeste homolog 2 (EZH2) that plays a critical role in the posttranslational regulation of EZH2 protein in GSCs. NEK2 was among the most differentially expressed kinase-encoding genes in GSC-containing cultures (glioma spheres), and it was required for in vitro clonogenicity, in vivo tumor propagation, and radioresistance. Mechanistically, the formation of a protein complex comprising NEK2 and EZH2 in glioma spheres phosphorylated and then protected EZH2 from ubiquitination-dependent protein degradation in a NEK2 kinase activity–dependent manner. Clinically, NEK2 expression in patients with glioma was closely associated with EZH2 expression and correlated with a poor prognosis. NEK2 expression was also substantially elevated in recurrent tumors after therapeutic failure compared with primary untreated tumors in matched GBM patients. We designed a NEK2 kinase inhibitor, compound 3a (CMP3a), which efficiently attenuated GBM growth in a mouse model and exhibited a synergistic effect with radiotherapy. These data demonstrate a key role for NEK2 in maintaining GSCs in GBM by stabilizing the EZH2 protein and introduce the small-molecule inhibitor CMP3a as a potential therapeutic agent for GBM.
Tobacco plan aims to produce England’s first smoke-free generation
Authors: Jacqui Wise
Journal: BMJ (2017)

The government’s new tobacco control plan for England sets out a vision of the first smoke-free generation, with a target to reduce the number of 15 year olds who regularly smoke from 8% to 3% or less by the end of 2025.1

The previous tobacco strategy for England expired at the end of 2015, and pressure has been growing for the government to renew its commitment to tackling smoking. In January The BMJ published a letter from more than 1000 doctors and other healthcare workers urging the government to publish a new tobacco control plan to tackle inequalities in health.23

The new tobacco control plan points out that 7.3 million adults in England …
Department of Health balances books—but at a price, say experts
Authors: Adrian O’Dowd
Journal: BMJ (2017)

Some parts of the NHS have been hit financially in the government’s drive to balance the books for the NHS overall, experts claim.

England’s Department of Health published its 2016-17 accounts on 18 July,1 showing that, although it has managed to end the most recent financial year in the black, this has been achieved at a cost to some aspects of the health service, such as lower investment in primary care and less spending on NHS building maintenance and equipment.

The figures show that the department underspent its revenue departmental expenditure limit—the part of the government’s budget allocated to and spent by government departments—by £563m in …
Primary cardioprotection in lymphoma patients with high risk of cardiovascular disease, treated with (R) CHOP regimen: A single center retrospective analysis.
Authors: Monika Dlugosz Danecka, Wojciech Jurczak, Agnieszka Olszanecka, Katarzyna Krawczyk, Aleksander B. Skotnicki
Journal: Journal of Clinical Oncology (2015)

e19515 Background: Advances in anti-lymphoma therapy and subsequent prolongation of overall survival, make doxorubicin cardiotoxicity an important clinical issue. Methods: Doxorubicin cardiotoxicity and efficacy of primary cardioprotection was assessed retrospectively in a single center analysis of 197 lymphoma patients treated at diagnosis with (R)-CHOP. 162 patients, including 62 with high risk of cardiovascular disease (CVD), were treated without primary cardioprotection. 35 patients, all with high CVD risk, who were subjected to primary cardioprotection with ACE-I and/or beta-blockers at the maximal tolerated doses. Patients with hypertension, diabetes mellitus, systolic or diastolic dysfunction in echocardiography and/ or cumulative doxorubicin dose exceeding 200 mg/m2 received liposomal doxorubicin. High CVD risk was defined by past medical history (PMH) as at least one of the following: hypertension, ischemic heart disease, cerebrovascular accidents, diabetes mellitus, hypercholesterolemia, nicotinism, arrhythmia or abdominal obesity. Additional value of NT-proBNP levels and spatial QRS-T angle assessment, as an independent indicators of individual sensitivity of cardiomyocytes to doxorubicin were also analyzed. Results: At the average observation time of 2 years, in patients without primary cardioprotection CVD was the second commonest cause of death: 5.5% (9/162) in the whole group, 14.5% (9/62) in patients with high risk of CVD. It was significantly reduced (0/35) in patients with primary cardioprotection, despite more CVD risk factors present (average 2.3 vs 1.71, p < 0.05). Primary cardioprotection also decreased the number of patients with systolic dysfunction at the end of therapy (3.03% vs 53%; p < 0.05), and frequency of new CVD related symptoms (2.86% vs 24.1 %; p < 0.05). The accuracy of determining high CVD risk based on PMH may be further increased by assessing NT-proBNP and spatial QRS-T angle after the first chemotherapy cycle (values > 400 pg/ml and > 90% respectively). Conclusions: The preliminary results are in favor of investigating the role of primary cardioprotection in specifically designed III phase trial.
Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist
Authors: Michael R. McKeown, M. Ryan Corces, Matthew L. Eaton, Chris Fiore, Emily Lee, Jeremy T. Lopez, Mei Wei Chen, Darren Smith, Steven M. Chan, Julie L. Koenig, Kathryn Austgen, Matthew G. Guenther, David A. Orlando, Jakob Lovén, Christian C. Fritz, Ravindra Majeti
Journal: Cancer Discovery (2017)

We characterized the enhancer landscape of 66 patients with acute myeloid leukemia (AML), identifying 6 novel subgroups and their associated regulatory loci. These subgroups are defined by their superenhancer (SE) maps, orthogonal to somatic mutations, and are associated with distinct leukemic cell states. Examination of transcriptional drivers for these epigenomic subtypes uncovers a subset of patients with a particularly strong SE at the retinoic acid receptor alpha (RARA) gene locus. The presence of a RARA SE and concomitant high levels of RARA mRNA predisposes cell lines and ex vivo models to exquisite sensitivity to a selective agonist of RARα, SY-1425 (tamibarotene). Furthermore, only AML patient-derived xenograft (PDX) models with high RARA mRNA were found to respond to SY-1425. Mechanistically, we show that the response to SY-1425 in RARA-high AML cells is similar to that of acute promyelocytic leukemia treated with retinoids, characterized by the induction of known retinoic acid response genes, increased differentiation, and loss of proliferation.Significance: We use the SE landscape of primary human AML to elucidate transcriptional circuitry and identify novel cancer vulnerabilities. A subset of patients were found to have an SE at RARA, which is predictive for response to SY-1425, a potent and selective RARα agonist, in preclinical models, forming the rationale for its clinical investigation in biomarker-selected patients. Cancer Discov; 7(10); 1136-53. ©2017 AACR.See related commentary by Wang and Aifantis, p. 1065.This article is highlighted in the In This Issue feature, p. 1047.
Does the extent of therapy differ between breast cancers detected by screening mammogram and non-screening methods?
Authors: Wendie-Lou D. Den Brok, Caroline Speers, Lovedeep Gondara, Alan Nichol, Christine Wilson, Caroline A. Lohrisch
Journal: Journal of Clinical Oncology (2017)

1544 Background: There is ongoing debate about the role of screening mammography and its impact on overall survival in breast cancer. We hypothesized that women with screen-detected breast cancers (SDBC) receive less surgery, regional radiotherapy (RRT), and chemotherapy (CH) than women with non-screen-detected breast cancers (NSDBC). Less therapy equates to less personal and societal burden, including less time away from work, fewer side effects, lower health care and disability costs, and reduced psychosocial distress. These may be adequate justification for screening programs even in the absence of an overall survival benefit. Methods: Women aged 40-79 years with stage 0-III breast cancers diagnosed between 2007-2012 and referred to the British Columbia Cancer Agency were identified using the Breast Cancer Outcomes Unit database. Clinical and tumor characteristics and type/extent of treatment were extracted. Linkage with the Screening Mammography Program of British Columbia segregated cases into SDBCs and NSDBCs. Interval breast cancers arising in regularly screened women (minimum 2-year interval) were excluded. Results: We identified 12,393 women; 7807 with SDBC and 4586 with NSDBC. Compared with NSDBCs, SDBCs were lower stage, less often treated with mastectomy and CH, and occurred in slightly older women (Table 1). SDBC received more radiation than NSDBC. Conclusions: Women with NSDBC are more likely to present with higher stage breast cancer. Rates of mastectomy and CH were 20% higher in NSDBC whereas SDBC had a modest 5% higher rate of RRT. These findings suggest that screening mammography decreases the extent of local and systemic treatment for breast cancer. [Table: see text]
Clinical Care Across Cultures
Authors: Margarita Alegría, Kiara Alvarez, Irene Falgas-Bague
Journal: JAMA Psychiatry (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 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
Cell of Origin and Double Protein Expression As Predictors of Outcome after Autologous Stem Cell Transplant for Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Who Undergo Intensive Consolidation Therapy (ICT) and Autologous Stem Cell Transplant (AutoSCT)
Authors: Bradley Hunter, Ben Rosen, Miguel Castillo, Lawrence D. Kaplan, Weiyun Z. Ai, Lloyd E. Damon, Thomas G. Martin, Charalambos Andreadis
Journal: Blood (2016)
38 Single centre experience with h.pylori eradication therapy
Authors: A Shahin, D McNamara
Journal: Gut (2017)

Background  Helicobacter pylori, is a gram-negative, microaerophilic bacterium usually found in the stomach and has been linked with chronic gastritis, gastric and duodenal ulcers, gastric cancer and MALT.  An increasing resistance to antibiotics has resulted in changes in the recommended eradication therapy.  The H.Pylori study group has recently updated the recommended eradication therapy.  Aim  To study the compliance with the updated therapy for H.Pylori infection.  Method  The prescriptions for triple therapy were collected and reviewed in compliance with the guidelines.  The results of the follow-up Urea Breath Test following completion of eradication therapy were recorded and the rate of successful eradication was compared in the group of patients who were treated according to the new recommendations versus old recommendations.  Results  The initial compliance with the new guidelines was 82%. Staff and junior doctor education have resulted in improvement in compliance rate.  Conclusions  1. Longer duration of therapy and more compliance with new guidelines has been associated with improved eradication therapy.  2. Confirming eradication of H.Pylori is an essential step in reducing and eliminating long term complications.
THE EFFICACY OF A NEUROMUSCULAR TRAINING INJURY PREVENTION WARM-UP PROGRAM IN JUNIOR HIGH SCHOOL STUDENTS
Authors: Sarah Richmond, Carla van den Berg, Oluwatoyosi Owoeye, Qian Shi, Luz Palacios-Derflingher, Brent Hagel, Alison Macpherson, Carolyn Emery
Journal: British Journal of Sports Medicine (2017)

Background Previous studies have established the efficacy of neuromuscular training (NMT) warm-up programs at reducing the risk of injury in youth in sport-specific contexts and, more recently, in a pilot study that included two Calgary junior high schools. Objective To determine the efficacy of iSPRINT (Implementing a School Prevention program to Reduce Injuries through Neuromuscular Training), a NMT warm-up program in reducing sport and recreational (S&amp;R) injuries. Design Cluster randomized controlled trial. Setting Junior high school physical education (PE) classes in Calgary, Alberta, Canada. Participants Students in grades 7–9, ages 11–16 years (n=429), from four of twelve junior high schools in the first of three study years. Interventions The iSPRINT NMT program was taught to and delivered by teachers as a S&amp;R injury prevention warm-up program in PE classes. Schools were randomized into the NMT intervention group or a control group (two schools per group). Main Outcome Measurements Incidence rate ratios (IRRs) were estimated using Poisson regression analyses to compare injuries between groups. Injuries were assessed by a physiotherapist or athletic therapist and included any S&amp;R injury that resulted in inability to return to the same activity, time loss from physical activity, or required medical attention. Results Injury rates (adjusted for hours of sport participation, previous injury, and clustering by class) were significantly lower in the intervention group (n=241) compared to the control group (n=188) for all sport injury (IRR=0.48, 95% CI; 0.26–0.91) and lower extremity injury (IRR=0.38, 95% CI; 0.20–0.74). Crude time loss injury rates (IRR=0.09, 95% CI; 0.02–0.45) and knee injury rates (IRR=0.18, 95% CI; 0.05–0.66) were also significantly lower in the intervention group. Conclusions These preliminary results suggest the efficacy of the iSPRINT program in reducing the risk of S&amp;R injury in a junior high PE context. This research will inform the public health impact of school-based injury prevention programs.
Effect of combined lamivudine and interferon alpha treatment on the T-cell response to HBV core peptides in paediatric patients infected with chronic hepatitis B virus.
Authors: M Cavers, M Aw, L D'Antiga, F Malacarne, R Williams, A Moorat, M Greensmith, M Atkins, G Mieli-Vergani, D Vergani
Journal: Hepatology (2001)
In vivo veritas: Finding novel genes involved in liver cancer through in vivo genetic screens
Authors: Cun Wang, René Bernards
Journal: Hepatology (2017)

1Division of Molecular CarcinogenesisThe Netherlands Cancer InstituteAmsterdamThe Netherlands 2State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
Abstract 261: Human IPS-Derived Cardiac Myocytes (hiPSC-CMs): How Good Are They as a Model for Cardiac Pacing and E-C Coupling?
Authors: Martin Morad, Xiao-Hua Zhang, Hua Wei, Lars Cleemann
Journal: Circulation Research (2013)

Derivation of cardiomyocytes from human induced pluripotent stem cells has opened a new field of biology where hiPSC-CM are being used as electrophysiological models of human cardiovascular physiology and pathology. Whether hiPS-CM represent also reliable Ca 2+ signaling and pacemaking models for the mammalian myocytes remains to be determined. Here we evaluate the EC-coupling and spontaneous pacemaking properties of human iPS-CM in detail and compare them to those of native mammalian myocytes. iPS-CMs, dissociated after ~40 days of differentiation and voltage-clamped at -50 mV, showed spontaneous beating and Ca 2+ oscillations that activated in-phase I NCX oscillations at holding potentials between -60 and +20mV, while I f activated negative to -75mV. Withdrawal of [Ca 2+ ] o and application of NCX-blocker (KBR- 7943) or tetracaine rapidly and reversibly inhibited spontaneous Ca 2+ -oscillations. Nifedipine and NO-synthase inhibitor L-NAME failed to alter spontaneous beating. Identical sets of data as these were also obtained from neonatal rat myocytes (NRM), suggesting that SR Ca 2+ release and uptake, and not I f , were responsible for spontaneous beating in NRM and hiPS-CM. Ca 2+ signaling parameters of hiPS-CM were also similar to those of adult atrial myocytes with Ca 2+ currents averaging ~8 pA/pF and I Ca -induced Ca 2+ -transients having a bell-shaped voltage-dependence similar to that of I Ca , consistent with Ca 2+ -induced Ca 2+ -release (CICR) mechanism. The ratio of I Ca -activated to caffeine-triggered Ca 2+ -transients was ~0.3, similar to the value in rat atria, but significantly smaller than the value of &gt;0.8 in ventricle. The gain of CICR was voltage-dependent as in adult cardiomyocytes. Adrenergic agonists enhanced I Ca , but elevated diastolic Ca 2+ . Ca 2+ -sparks were sporadic and brief in duration (&lt; 25ms). Our data suggest that hiPS-CM have all the specific characteristics of adult cardiomyocytes and the mechanisms of their spontaneous pacing are similar to those found in NRM, and involve Ca 2+ cross-talk between NCX, RyR/SR, and possibly mitochondria.
Multiparametric Flow Fytometry Is More Useful Than Cytology As a Diagnostic Tool for Endoscopic and Transbronchial Ultrasound-Guided Fine Needle Aspiration Samples in Hematological Malignancies: A Single Center Experience
Authors: Luis García, José A. Calvo, Mya Hae Tha, Oscar Blanco, Antonio Velasco, Rosa Cordovilla, Noemi Puig, Alejandro Martín, Oscar Ferre, Felix López, Nerea Arratibel, Mónica Baile, Alvaro Veiga, Javier Carrillo, Alejandro Avendaño, Daniel Rivera, Consuelo Del Cañizo, Belen Vidriales
Journal: Blood (2016)