tbuckley/cabot-search huggingface dataset:
Clinician Perspectives on Current Issues in Lung Cancer Drug Development
Authors: Saiama N. Waqar, Philip D. Bonomi, Ramaswamy Govindan, Fred R. Hirsch, Gregory J. Riely, Vassiliki Papadimitrakopoulou, Dickran Kazandjian, Sean Khozin, Erin Larkins, Dane J. Dickson, Shakun Malik, Leora Horn, Andrea Ferris, Alice T. Shaw, Pasi A. Jänne, Tony S.K. Mok, Roy Herbst, Patricia Keegan, Richard Pazdur, Gideon M. Blumenthal
Journal: Journal of Thoracic Oncology (2016)
National body is considering a single register for all health and care professionals
Authors: Adrian O’Dowd
Journal: BMJ (2016)

The body that oversees the major regulators of health professionals in the UK is considering the idea of a single register in order to stop people who have been struck off from practising under a different title.

The lead officers of the Professional Standards Authority (PSA) appeared before the parliamentary health committee for a one off evidence session on 5 July to answer questions about the authority’s performance as well as that of the professionals’ regulators.

The PSA oversees the General Medical Council and equivalent organisations for dentists, nurses, pharmacists, and other health and care professionals.

MPs asked if the authority considered having one register in the future that would apply across health and care to enable a check …
Genetic dissection of the α-globin super-enhancer in vivo
Authors: Deborah Hay, Jim R Hughes, Christian Babbs, James O J Davies, Bryony J Graham, Lars L P Hanssen, Mira T Kassouf, A Marieke Oudelaar, Jacqueline A Sharpe, Maria C Suciu, Jelena Telenius, Ruth Williams, Christina Rode, Pik-Shan Li, Len A Pennacchio, Jacqueline A Sloane-Stanley, Helena Ayyub, Sue Butler, Tatjana Sauka-Spengler, Richard J Gibbons, Andrew J H Smith, William G Wood, Douglas R Higgs
Journal: Nature Genetics (2016)
Multidisciplinary Treatment Outcome of Desmoid-Type Fibromatosis (Dtf). a Registry-Based Study from Spanish Group for Research on Sarcoma (Geis)
Authors: J. Martinez-Trufero, R. Alvarez Alvarez, A. Lopez Pousa, I. Sevilla, P. Sancho Marquez, C. Orbegoso, J. Cruz Jurado, M.A. Sala Gonzalez, C. Valverde Morales, M.J. Blanco Sanchez, J.A. Pérez-Fidalgo, J.P. Berros, J. Martinez García, J.L. Arranz, A. Meana, J.A. López-Martín, J. Rubió, J.M. Cano, I. Juez-Martel, J. Martin Broto
Journal: Annals of Oncology (2014)
COXEN prediction of antineoplastic drug sensitivity in bladder cancer patients.
Authors: Shalin Kothari, Daniel Gustafson, Keith Killian, James Costello, Daniel C. Edelman, Jennifer Walling, Paul S. Meltzer, Dan Theodorescu, Andrea B. Apolo
Journal: Journal of Clinical Oncology (2016)

365 Background: COXEN (Co-eXpression ExtrapolatioN) uses molecular profiles as a “rosetta stone” for translating drug sensitivities of one set of cancers into predictions for another completely independent set of cell lines or human tumors. The ability of COXEN to predict drug effectiveness in pts using tumor samples from in vitro assays is unique. Methods: We tested the predictive value of COXEN for standard chemotherapies in a cohort of bladder cancer pts. Total RNA was extracted from formalin fixed paraffin embedded (FFPE) tissue and converted to cDNA, amplified with Ovation FFPE WTA, and hybridized to a GeneChip Human Genome U133 Plus 2.0 array. Using gene expression data from 278 independent bladder tumors, COXEN scores were generated using bioinformatics models originally built using the NCI-60 cell line panel and a model building algorithm (MiPP). Gene expression data was processed to score 76 FDA approved antineoplastic drugs. Results: A total of 24 samples were tested (15 tumors with 1 sample and 9 tumors with 2 biological replicas (2 samples from the same tumor)) from 15 pts who received chemotherapy (median age 64 (41-74); 73% male; with muscle invasive bladder cancer (MIBC) (12/15, 80%) or metastatic bladder cancer (mBC) (3/15, 20%)). Response to therapy was confirmed by pathologic response in MIBC pts and radiologic response in mBC pts. Chemotherapies evaluated included: methotrexate/vinblastine/doxorubicin/cisplatin; gemcitabine/cisplatin; gemcitabine/carboplatin; and cisplatin/etoposide. COXEN accurately predicted antineoplastic drug sensitivity in 11/15 (73%) pts (75% MIBC and 67% mBC), of which 7/11 pts had 2 biological samples. However, only 3/7 (43%) biological replicas confirmed COXEN prediction. COXEN accurately predicted drug sensitivity in 9/10 (90%) pts with response and 2/5 (40%) pts with resistance to therapy. Conclusions: COXEN did well in predicting antineoplastic drug response for the majority of bladder cancer pts in this cohort. However, predictions from 2 samples within the same tumor were not always consistent, likely due to the expected tumor heterogeneity found in bladder cancer tumors. A prospective clinical trial in patients with mBC using COXEN to select next best therapy is in development.
Providing a conceptual framework for HIV prevention cascades and assessing feasibility of empirical measurement with data from east Zimbabwe: a case study
Authors: Geoffrey P Garnett, Timothy B Hallett, Albert Takaruza, James Hargreaves, Rebecca Rhead, Mitchel Warren, Constance Nyamukapa, Simon Gregson
Journal: The Lancet HIV (2016)

The HIV treatment cascade illustrates the steps required for successful treatment and is a powerful advocacy and monitoring tool. Similar cascades for people susceptible to infection could improve HIV prevention programming. We aim to show the feasibility of using cascade models to monitor prevention programmes.Conceptual prevention cascades are described taking intervention-centric and client-centric perspectives to look at supply, demand, and efficacy of interventions. Data from two rounds of a population-based study in east Zimbabwe are used to derive the values of steps for cascades for voluntary medical male circumcision (VMMC) and for partner reduction or condom use driven by HIV testing and counselling (HTC).In 2009 to 2011 the availability of circumcision services was negligible, but by 2012 to 2013 about a third of the population had access. However, where it was available only 12% of eligible men sought to be circumcised leading to an increase in circumcision prevalence from 3·1% to 6·9%. Of uninfected men, 85·3% did not perceive themselves to be at risk of acquiring HIV. The proportions of men and women tested for HIV increased from 27·5% to 56·6% and from 61·1% to 79·6%, respectively, with 30·4% of men tested self-reporting reduced sexual partner numbers and 12·8% reporting increased condom use.Prevention cascades can be populated to inform HIV prevention programmes. In eastern Zimbabwe programmes need to provide greater access to circumcision services and the design and implementation of associated demand creation activities. Whereas, HTC services need to consider how to increase reductions in partner numbers or increased condom use or should not be considered as contributing to prevention services for the HIV-negative adults.Wellcome Trust and Bill & Melinda Gates Foundation.
Metabolic Characteristics of 16HBE and A549 Cells Exposed to Different Surface Modified Gold Nanorods
Authors: Zhigang Liu, Liming Wang, Limin Zhang, Xiaochun Wu, Guangjun Nie, Chunying Chen, Huiru Tang, Yulan Wang
Journal: Advanced Healthcare Materials (2016)

Gold nanorods (AuNRs) have shown their great potential in cancer treatment due to their special physiochemical and optical properties, and the ease of surface modification. However, the molecular mechanism of biological effects induced by different surface modified AuNRs remains largely undetermined. Herein, this study for the first time systematically analyzed metabolic impacts of three surface modified AuNRs in cancer and noncancer cells detected by NMR and GC‐FID/MS metabolomics and validated by molecular biological approach. It is found that positively and negatively charged AuNRs induce different metabolic consequences. Most importantly, it is found that the PEI‐AuNRs display specific cytotoxicity to A549 cells while posing little impact on 16HBE cells. The cytotoxicity of PEI‐AuNRs to A549 cells is manifested in large disruptions to the cell metabolisms, which affects energy metabolism, choline metabolism, the hexosamine biosynthesis pathway, and oxidative stress to cells. The results of this study provide comprehensive molecular information on the distinct biological effects of different surface modified AuNRs, and can be valuable in designing purpose‐driven nanomaterials. Most importantly, this work highlights the potential of metabolomics coupled with molecular biological techniques in screening antitumor nanodrugs and revealing the molecular mechanism of their biological effects.
Quality Control
Authors: PAUL E. BERMAN
Journal: Annals of Internal Medicine (1975)

Comments and Corrections1 March 1975Quality ControlPAUL E. BERMAN, M.D.PAUL E. BERMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-82-3-424 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I wish to take issue with the principle of "comprehensive statistical monitoring" presented by Dr. Virgil Slee in "PSRO and the Hospital's Quality Control" (Ann Intern Med 81:97-106, 1974).Some shortcomings have been discovered in this method of review. The first is that in at least three studies done at our institution on the subject of myocardial infarction using diagnostic criteria of a positive ECG, or elevated enzymes plus a suspicious ECG, there was a frequency of incorrect diagnosis of from 3% to 15%. Because Dr. Slee's system has never included an effective diagnosis screen (the diagnosis...References1. : The Pep Primer, Chicago, 1974 Google Scholar2. : Quality Assurance Monitor, Ann Arbor, Michigan, June 1974 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: PAUL E. BERMAN, M.D.Affiliations: 21 Mayo Road Holden, Massachusetts 01520 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1975Volume 82, Issue 3 Page: 424-425 Keywords Enzymes Myocardial infarction Professional standards review organizations Quality improvement ePublished: 1 December 2008 Issue Published: 1 March 1975 PDF downloadLoading ...
Colleges support “yes” vote on new junior doctor contract
Authors: Abi Rimmer
Journal: BMJ (2016)

The royal colleges have expressed their support for the proposed new contract for junior doctors and have urged their members to accept it.

Junior doctors and final or penultimate year medical students in England will vote on whether to accept or reject the proposed new contract between 17 June and 1 July.

Jane Dacre, president of the Royal College of Physicians, issued a statement encouraging junior doctors to accept the proposed contract.1 She said, “I know that opinion is likely to be split but, after a lot of thought about what I would do if I were …
Effect of therapeutic targeting of the oncogene EMP2 in triple-negative breast cancer on tumor load.
Authors: Madhuri Wadehra, Meagan Kiyohara, Maoyong Fu, Lynn K Gordon, Jonathan Braun
Journal: Journal of Clinical Oncology (2012)

1052 Background: Understanding tumor induced angiogenesis is a challenging problem with important consequences for the diagnosis and treatment of cancer. In this study we define a novel function for the tetraspan epithelial membrane protein-2 (EMP2) in the control of neoangiogenesis. EMP2 is an oncogene whose expression has been shown to correlate with tumor progression and survival in a number of human cancers including triple negative breast, ovarian, and endometrial tumors. In breast cancer, EMP2 is highly expressed on the majority of invasive tumors examined, and in particular 70% of triple negative breast tumors showed surface expression of this marker. In this study, we examine the control of EMP2 on the tumor microenvironment and further characterize its therapeutic efficacy in breast cancer. Methods: A number of cancer cell lines were utilized both in vitro and in vivo to determine if EMP2 expression levels altered the tumor microenvironment. Cells were tested for their expression of pro-angiogenic proteins HIF-1a and VEGF-A as well as for their ability to induce endothelial cell migration and capillary like tube formation. Cells with modulated EMP2 levels were also tested in vivo for tumor formation and examined for histological changes in the tumor microenvironment. In addition, we recently constructed a fully human EMP2 IgG1 and determined its therapeutic efficacy in a number of triple negative breast cancer cells. Results: In vitro, upregulation of EMP2 promoted VEGF expression through a HIF-1a dependent pathway and resulted in successful capillary-like tube formation. In contrast, reduction of EMP2 correlated with reduced HIF-1a and VEGF expression with the net consequence of poorly vascularized tumors in vivo. Treatment of breast cancer cells with EMP2 IgG1 reduced tumor load with a significant improvement in survival. Conclusions: Clinically, EMP2 has been shown to correlate with poor survival, and these results suggest that this occurs in part through its control on tumor vasculature. In addition, we provide additional evidence on the potent cytotoxic effects of EMP2 treatment in vivo.
CDK4/6 Inhibitors: Promising Opportunities beyond Breast Cancer
Authors: Joline S.J. Lim, Nicholas C. Turner, Timothy A. Yap
Journal: Cancer Discovery (2016)

Abstract Summary: Patnaik and colleagues report on the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of abemaciclib for the treatment of advanced solid cancers, demonstrating antitumor activity in advanced breast cancers as well as glioblastoma, melanoma, non–small cell lung cancer, colorectal cancer, and ovarian cancer. The development of abemaciclib and other CDK4/6 inhibitors should now be fully optimized through the use of novel predictive biomarkers of response and rational combinations. Cancer Discov; 6(7); 697–9. ©2016 AACR. See related article by Patnaik et al., p. 740.
Development Of t-MDS In Patients Undergoing Autologous Transplantation For Lymphoma Is Not Associated With Increased Frequency Of Mitochondrial DNA Mutations
Authors: Becky Pinjou Tsai, Liang Li, Min Li, Patrick Halliday, Anastasia Rosales, Stephen J. Forman, Smita Bhatia, Ravi Bhatia
Journal: Blood (2013)
Surveillance de la légionellose dans un hôpital en Italie du Nord, mai 1998 à septembre 1999
Authors: P Borella, A Bargelini, S Pergolizzi, R Mazzuconi, G Gesu, R Vaiani, G Stancanelli, P Nizzero, C Curti, G Aggazzotti
Journal: Eurosurveillance (1999)

En 1997, l'incidence de la legionellose en Europe etait de 3,9 cas par million d'habitants. Les incidences les plus faibles etaient rapportees a Malte (0) et en Norvege (0,2), et la plus elevee au Danemark (24) (1). L'Italie n'a declare que 90 cas (1,5 cas/million d'habitants), dont 20% d'origine nosocomiale (2), mais les legionelloses non diagnostiquees et la sous-declaration semblent la raison principale de cette faible incidence.
A phase II trial of afatinib (BIBW 2992) in patients (pts) with advanced non-small cell lung cancer previously treated with erlotinib (E) or gefitinib (G).
Authors: N. Yamamoto, N. Katakami, S. Atagi, T. Hida, K. Goto, T. Horai, A. Inoue, Y. Ichinose, K. Kobayashi, K. Takeda, K. Kiura, H. Saka, T. Tamura, I. Okamoto, N. Nogami, R. Morinaga, K. Nishio, Y. Seki, R. M. Lorence, M. Shahidi
Journal: Journal of Clinical Oncology (2011)

7524 Background: An unmet medical need exists in NSCLC pts after failure of E or G [reversible EGFR tyrosine kinase inhibitors (TKIs)], particularly in pts with T790M EGFR mutations, the most common mechanism of acquired resistance. Afatinib (A), an irreversible erbB family blocker, has preclinical activity against T790M. A was tested in this phase II study in pts enriched for acquired resistance to E or G. Methods: Pts in Japan with Stage IIIB/IV NSCLC (ECOG PS 0–1) who had progressed according to RECIST after 1–2 lines of chemotherapy and ≥12 wks of E or G received 50 mg A orally qd. The primary endpoint was objective tumor response. Results: Of 62 pts (F:48; M:14), 11.3%, 79% and 9.7% had received prior erlotinib, gefitinib or both, respectively. 65% of pts had achieved a prior response with E/G. Median duration between end of prior treatment with E/G and the start of A was 3 wks. 73% of pts were EGFR mutation-positive in their primary tumors. 82% of pts met the definition of acquired resistance to E/G by (1) EGFR mutation positive or (2) CR/PR to E/G or (3) SD for at least 6 months to E/G and (4) less than 4 wks off E/G. By investigator assessment, 13% of pts treated with A had a PR and the disease control rate (DCR >8 wks) was 72%; these values were 8.2% and 67%, respectively, by independent review. Median PFS was 4.6 months. Similar efficacy was seen in those pts meeting acquired resistance criteria (5.9% PR; 69% DCR; median PFS of 4.4 months, by independent review). Two pts had T790M mutations in their primary tumors; one, harbouring L858R+T790M, had a long SD (308 days). At data cut-off, the 25th percentile of OS was 10.6 months. Common adverse events included diarrhea, rash/acne, stomatitis, nail effects and decreased appetite. Conclusions: Pts in this study largely meet criteria for acquired resistance to first generation EGFR TKIs in NSCLC. Afatinib has demonstrated clinically meaningful efficacy (including 69% DCR >8 wks and 4.4 month median PFS) in these pts.
State of the Art for Deep Brain Stimulation Therapy in Movement Disorders: A Clinical and Technological Perspective
Authors: Aparna Wagle Shukla, Michael S. Okun
Journal: IEEE Reviews in Biomedical Engineering (2016)

Deep brain stimulation (DBS) therapy is a widely used brain surgery that can be applied for many neurological and psychiatric disorders. DBS is American Food and Drug Administration approved for medication refractory Parkinson's disease, essential tremor and dystonia. Although DBS has shown consistent success in many clinical trials, the therapy has limitations and there are well-recognized complications. Thus, only carefully selected patients are ideal candidates for this surgery. Over the last two decades, there have been significant advances in clinical knowledge on DBS. In addition, the surgical techniques and technology related to DBS has been rapidly evolving. The goal of this review is to describe the current status of DBS in the context of movement disorders, outline the mechanisms of action for DBS in brief, discuss the standard surgical and imaging techniques, discuss the patient selection and clinical outcomes in each of the movement disorders, and finally, introduce the recent advancements from a clinical and technological perspective.
Avelumab (MSB0010718C; anti-PD-L1) as a first-line treatment for patients with advanced NSCLC from the JAVELIN Solid Tumor phase 1b trial: Safety, clinical activity, and PD-L1 expression.
Authors: Claire F. Verschraegen, Franklin Chen, David R. Spigel, Nicholas Iannotti, Edward Francis McClay, Charles H. Redfern, Jaafar Bennouna, Matthew H. Taylor, Howard Kaufman, Karen Kelly, Marcis Bajars, Anja von Heydebreck, Jean-Marie Cuillerot, Guy Heinrich Maria Jerusalem
Journal: Journal of Clinical Oncology (2016)

9036 Background: Avelumab* is a fully human anti-PD-L1 IgG1 antibody under clinical investigation in multiple cancers. We report safety and clinical activity of avelumab as 1st-line therapy in patients (pts) with non-small-cell lung cancer (NSCLC) from a phase 1b trial (NCT01772004). Methods: Pts with advanced NSCLC not previously treated systemically for metastatic or recurrent disease, without an activating EGFR mutation or ALK rearrangement, and not selected for PD-L1 expression were treated with avelumab 10 mg/kg IV Q2W until progression, unacceptable toxicity, or withdrawal. Responses were evaluated every 6 wks (RECIST 1.1). Adverse events (AEs) were graded by NCI-CTCAE v4.0. PD-L1 expression was assessed by IHC. Results: As of Oct 23, 2015, 145 pts received avelumab (median 10 wks [range 2-30]) and were followed for a median duration of 13 wks (range 0-31). Median age was 70 y (range 41-90), ECOG PS was 0 (31.0%) or 1 (69.0%), and histology was adenocarcinoma (63.4%), squamous (26.9%), other (3.4%), or unknown (6.2%). Treatment-related (TR) AEs occurred in 82 pts (56.6%; all grades); those occurring ≥ 10% were infusion-related reaction (IRR; 24 [16.6%]) and fatigue (21 [14.5%]). Grade ≥ 3 TRAEs were reported in 13 pts (9.0%); only IRR and fatigue occurred in > 1 pt (each 3 [2.1%]). There were no treatment-related deaths. Among 75 pts with ≥ 3 mos f/u, unconfirmed ORR was 18.7% (95% CI: 10.6, 29.3) based on 1 CR and 13 PRs; 12 were ongoing. Stable disease was reported in 34 pts (45.3%); disease control rate was 64.0%. PD-L1 expression was evaluable in 45/75 pts (60.0%). Based on a ≥ 1% cutoff for tumor cell staining, 35/45 (77.8%) were PD-L1+ and ORR was 20.0% in PD-L1+ (7/35; 95% CI: 8.4, 36.9) vs 0/10 (0.0, 30.8) in PD-L1– pts. Median PFS was 11.6 wks (95% CI: 6.7, 17.9) for all treated pts. Conclusions: Single-agent avelumab showed an acceptable safety profile and clinical activity in pts with NSCLC who were EGFR-wildtype and ALK-negative, not previously treated for advanced disease, and unselected for PD-L1 expression. A trend of higher ORR in PD-L1+ tumors is suggested. Phase 3 trials of avelumab in NSCLC are ongoing. *Proposed INN. Clinical trial information: NCT01772004.
Aortic Angulation Attenuates Procedural Success Following Self-Expandable But Not Balloon-Expandable TAVR
Authors: Yigal Abramowitz, Yoshio Maeno, Tarun Chakravarty, Yoshio Kazuno, Nobuyuki Takahashi, Hiroyuki Kawamori, Geeteshwar Mangat, Wen Cheng, Hasan Jilaihawi, Raj R. Makkar
Journal: JACC. Cardiovascular imaging (2016)
Impact of Treatment On CD4+CTLA-4+ T Cell Subset in Brazilian Patients with Classical Hodgkin Lymphoma
Authors: Joyce M. K. Silva, Maria Mirtes Sales, Adriana M. Damasco Penna, Elma Maria Chaves Maria Chaves, Priscilla B Silva, Mariane Cristina Gennari Assis, Otávio Cesar Carvalho Guimarães Baiocchi
Journal: Blood (2012)
Sonographic diagnosis of transhepatic placement of a percutaneous endoscopic gastrostomy (PEG) tube
Authors: Toni Herta, Martin Hecker, Florian van Boemmel, Albrecht Hoffmeister, Thomas Karlas
Journal: Endoscopy (2015)

A 44-year-old patient with cachexia and insufficient oral intake due to hypopharyngeal carcinoma underwent percutaneous endoscopic gastrostomy (PEG) placement with the pull technique, which is a common option for the treatment of dysphagia [1]. Transillumination and finger pressure revealed a safe puncture site at the anterior gastric wall, and the PEG tube was placed without complications at the time of the intervention. Initial tube feeding went properly, and the patient was discharged the next day.
Enhancement of memory processes in Alzheimer's disease with multiple- dose intravenous physostigmine
Authors: K L Davis, R C Mohs
Journal: American Journal of Psychiatry (1982)

Physostigmine (.125 mg, .25 mg, or .50 mg) or placebo was administered intravenously to 10 neuroleptic-free patients with Alzheimer's disease over a 30-minute period. All patients performed better on a recognition memory task while receiving physostigmine. When placebo or the dose of physostigmine previously associated with an improvement in memory was readministered, physostigmine again enhanced performance on a recognition memory task. These results indicate that the acute augmentation of cholinergic activity in some patients with Alzheimer's disease can partially reverse the memory deficit of that disorder and may provide an approach to the eventual therapy of this condition.