tbuckley/cabot-search huggingface dataset:
Proline oxidase (dehydrogenase) generates switchable bioenergetics for cancer cell survival or programmed cell death
Authors: James Phang, Jui Pandhare, Yongmin Liu
Journal: Cancer Research (2008)

4934   Cancer cells survive by surmounting temporal and spatial gauntlets of stress. Identifying and targeting these stress responders may lead to novel regimens for cancer prevention and treatment. With proline mobilized in the tumor microenvironment from matrix metalloprotein-ases-dependent collagen degradation, cancer cells can activate proline oxidase (dehydrogenase) as a stress responder for either bioenergetics or to produce mediators of programmed cell death. Bound to mitochondrial inner membranes, proline oxidase (POX) is encoded by a p53-induced gene, and it generates mitochondrial superoxide. Overexpression of POX in DLD-tet-off-POX colorectal cancer cells initiated apoptosis by both intrinsic (mitochondrial) and extrinsic (death receptor) pathways. Co-expression of superoxide dismutase 2 (SOD2) in mitiochondria blocked these effects. POX is also induced by PPARγ and its pharmacologic ligands, the thiazolidinediones. The PPARγ-dependent ROS in cancer cells is markedly decreased by knockdown of POX with antisense or siRNAs in colorectal cancer cells and non-small-cell lung cancer cells. The linkage to genotoxic and inflammatory stress suggested that POX may also be important during nutrient stress as invading cancer cells become isolated from their blood supply. Indeed, this was the case as glucose depletion downregulated mTOR-mediated phosphorylation of S6 kinase but upregulated POX more than 5-fold. The mediation by mTOR was established by showing that Rapamycin or AICAR upregulated POX.more than 10-fold. Under these conditions, Rapamycin modulated bioenergetics to maintain ATP levels in the cell, and POX was involved since the Rapamycin effect was decreased by inhibition of POX catalytic activity with dehydroproline. These findings show that POX is a critical responder to genotoxic, inflammatory and nutrient stress. Recent structural biology characterization by others suggested that POX contains a “switching” mechanism for production of ATP for bioenergetics as well as ROS for programmed cell death. Depending on the specific stress, POX can use proline-derived electrons to reduce oxygen generating superoxide for programmed cell death or donate electrons to the electron transport chain yielding ATP.
AB0630 Clinical spectrum time course comparison between PL-7, PL-12 and EJ positive antisynthetase syndrome
Authors: E Trallero Araguas, A O'Callaghan Selva, CA Scire, V Codullo, S Castaneda, N Ortego Centeno, JA Pereira da Silva, C Fiehn, A Schwarting, A Manfredi, G Emmi, S Barsotti, O Molberg, A Doria, S Parisi, S Scarpato, N Pipitone, M Piga, I Cavazzana, FJ Lopez-Longo, J Bachiller-Corral, M Benucci, J Rojas-Serrano, K Triantafyllias, N Perez-Gomez, G Cagnotto, F Maurier, L Quartuccio, E Bartoloni Bocci, P Tomietto, R Caporali, F Iannone, MA Gonzalez-Gay, L Cavagna
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Arthritis, myositis and Interstital lung disease (ILD) represent the classic clinical triad of antisynthetase syndrome (ASSD). In anti Jo-1 positive patients, these findings may appear also during the follow-up. Even if a similar cumulative trend has been showed also in non anti Jo-1 positive ASSD, a head to head comparison of clinical spectrum time course in these patients is still lacking <h3>Objectives</h3> To assess the clinical spectrum time course in non anti Jo-1 positive ASSD, according to different underlying non anti Jo-1 specificities <h3>Methods</h3> Clinical, laboratory and instrumental data collection of anti PL-7, PL-12, and EJ positive patients from an international database of ASSD <h3>Results</h3> We identified 63 (42%) anti PL-7, 66 (44%) anti PL-12 and 20 (14%) anti EJ positive patients, reporting their characteristics in table 1 (disease onset) and 2 (last follow-up). At disease onset, no substantial differences were observed. At the end of follow-up, we observed some differences between anti PL-12 and both anti PL-7 and anti-EJ positive patients. In particular, anti PL-12 positive patients presented less frequently ex-novo triad findings and had a reduced prevalence of myositis. From the clinical point of view, the main pattern of disease presentation was an isolated ILD in all groups at the onset and only in anti-PL12 positive ASSD at last follow-up. <h3>Conclusions</h3> Our study seems to indicate that clinical spectrum time course of anti PL-12 positive ASSD is different from that of anti PL7 and of anti EJ positive ASSD. The clinical pattern associated with these two latter antibodies was very similar. Furthermore, anti PL-12 positive patients seems to have a more stable disease, with a less common occurrence of ex-novo triad findings during the follow-up <h3>References</h3> Cavagna L. Medicine 2015. Cavagna L. CRAI 2016. Cavagna L. ARD 2016 (Abstract). Trallero Araguas E. Scand J Rheumatol 2016. <h3>Acknowledgements</h3> To all members of the AENEAS collaborative group. <h3>Disclosure of Interest</h3> None declared
AB0838 Epidemiology and analysis of falls in patients during balneotherapy in danubius health spa piestany
Authors: I Rybar, V Kolnikova, T Zimanova, R Gaspar
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Patients falls in hospitals are frequent and undesirable complications that may lead to negative outcomes such as injuries, prolonged hospitalization and legal liability. <h3>Objectives</h3> To investigate the incidence and characteristics of patients hospitalized in the Health Spa Piestany. <h3>Methods</h3> Prospective analysis of falls in the group of in-patients of health spa during a year since 01.01.2015 to 31.12.2015. <h3>Results</h3> Overall there were hospitalized in the health spa 25 774 in-patients. The mean age of patients was 64,02±13,16 years. There were women - 15 301, mean age (63,61±11,57 years) and men 10 473, with mean age (64,43±9,22 years). Falls were confirmed in 131 patients (women 94, mean age 68,55±10,22 years and men 37 males, mean age 70,39±7,62 years. Fractures have been confirmed in 19 patients, all of them non-vertebral. The ankle distortion were in 11 patients and lacerated wounds in 10 patients. There were collapse status in 8 and commotio cerebri in 1 patient. Spa therapy had to be discontinued only in 5 from 131 patiens due to falls. The annual incidence of falls reached 5,08 cases/1000 patients. In women there were - 6,14 cases/1000 women a year and in men 3,53 cases/1000 men a year. The annually incidence of fractures reached 0,69/1000 pacients. The most common locations of falls were hotel rooms, especially bathtub in the bathroom (49%), slightly less facilities for balneotherapy (22%), the area outside the spa (21%) and at least in the park area of health spa 8%. Women and men who have suffered falls had significantly higher age and had also high rate of cardio-vascular morbidity (87%). <h3>Conclusions</h3> The annual incidence of falls among patients in a balneotherapy reached to 5.08 cases per 1,000 patients per year. Incidence of falls in women was almost twice as high compared to men. The age of women and men with falls was significantly higher (p&lt;0,001) compared to other patients and they also had higher rate of cardiovascular morbidity. The most common locations of falls were bathtubs in the bathroom. <h3>References</h3> Gazibara T. et al.: Psychogeriatrics. 2017 Jan 27. doi: 10.1111/psyg.12217. Cockayne S. et al.: PLoS One. 2017 Jan 20;12(1):e0168712. Tsonga T. et al.: Clin Orthop Surg. 2015 Dec;7(4):449–56. <h3>Disclosure of Interest</h3> None declared
SAT0083 Tocilizumab induced clinical remission in rheumatoid arthritis had more residual doppler signals in comparison with other biologics
Authors: Y Hara, Y Ishida, Y Yamaguchi, Y Yoshimine, T Wibowo, Y Manabe, M Yaga, K Kawamoto, H Nakahara, S Higa, T Igarashi, K Maeda, A Ogata
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To study the residual Power Doppler (PD) signals for assessing synovitis in CRP negative patients with rheumatoid arthritis (RA) treated with biologics. <h3>Methods</h3> Biologics treated RA patients who were maintained normal CRP for more than 6months (34 TNF inhibitors, 37 Tocilizumab, 23 Abatacept) were assessed by ultrasonography. Residual PD signals were assessed in MCP, PIP, and wrist joints with both hands. We assumed patients who had any PD signals in assessed joints were "residual PD signals". <h3>Results</h3> All treated patients with biologics maintained normal CRP for a half year (n=94). 35.1% of patients treated with biologics had positive PD signals. The remission rates of DAS28-ESR, CDAI, and Boolean were 68.7%, 62.8%, and 48.9% respectively. 28.1% of patients who achieved DAS28-ESR remission had residual PD signals, 22.0% in CDAI, and 21.7% in Boolean. 23.8% of patients treated by TNF inhibitors who achieved DAS28-ESR remission had residual PD signals, 34.6% in Tocilizumab, and 20.0% in Abatacept. In case of setting the DAS28-ESR remission less than 3.0, 30.2% of patients who achieved DAS28-ESR remission had residual PD signals, 29.0% in less than 2.0, and 12.5% in less than 1.5. The patients who have no tender or swollen joints and the excellent patient oriented global health assessment (VAS score was zero) had fewer residual PD signals (23.4% vs 58.6% in tender joints, 26.7% vs 66.7% in swollen joints, and 13.3% vs 44.4% in patient VAS). <h3>Conclusions</h3> The patients who achieved clinical remission had residual PD signals. Patients with Tocilizumab induced remission had more residual PD signals compared with TNF inhibitor or Abatacept induced remission. More strict criteria of clinical remission may reduce residual PD signals in patients treated by Tocilizumab. <h3>Disclosure of Interest</h3> None declared
Thank you and goodbye!
Authors: Tore K Kvien
Journal: Annals of the Rheumatic Diseases (2017)

I am grateful for the opportunity to be Editor in Chief for Annals of the Rheumatic Diseases ( ARD ) since 1st of April 2008. I was fortunate to succeed Professor Leo van de Putte who had been the successful Editor of this European League Against Rheumatism (EULAR) journal since 1999.1 Importantly, he was my teacher when I started.2 Editorial responsibility for a leading scientific journal means that you need to cover a broad area, that is, research work from ‘bench to bedside’. My first step was actually to identify weaknesses in my own knowledge and invite experts in these areas as associate editors or editorial board members to fill these gaps of knowledge. These colleagues have all been extremely important for the increasing success of ARD during the …
SP0161 The role of adipose tissue in osteoarthritis
Authors: A Ioan-Facsinay
Journal: Annals of the Rheumatic Diseases (2017)

The association between obesity and osteoarthritis (OA) is nowadays well-accepted. This association is present both in weight-bearing and non-weight-bearing joints, indicating that next to local effects, systemic effects associated with obesity could play a role in disease. The relative contribution of local and systemic effects could be different in each joint. In this presentation, I will summarize the current knowledge about the contribution of local and systemic adipose tissues to osteoarthritis in different joints, with emphasis on knee OA. Moreover, obesity-associated changes and their role in OA will be highlighted. The key messages I would like to convey are: Mechanical stress is a major contributor to knee OA The infrapatellar fat pad (IFP), an intra-articular adipose tissue in the knee, is dostinct from other adipose tissues and could play a role in knee OA Only few obesity-related features have been described in IFP in OA <h3>Disclosure of Interest</h3> None declared
Annals Story Slam - Warren and Wilfred
Authors: Robert Sargeant
Journal: Annals of Internal Medicine (2017)

Web Exclusives19 September 2017Annals Story Slam - Warren and WilfredFREERobert Sargeant, MDRobert Sargeant, MDFrom University of Toronto, Toronto, Ontario, Canada.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W17-0058 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Warren and Wilfred "Warren and Wilfred," by Dr. Robert Sargeant (Duration 07:14)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From University of Toronto, Toronto, Ontario, Canada.Current Author Address: Robert Sargeant, MD, University of Toronto, Toronto, Ontario, Canada; e-mail, [email protected]ca. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 September 2017Volume 167, Issue 6Page: SS1 ePublished: 19 September 2017 Issue Published: 19 September 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.Loading ...
Differential response to doxorubicin in breast cancer subtypes simulated by a microfluidic tumor model
Authors: Altug Ozcelikkale, Kyeonggon Shin, Victoria Noe-Kim, Bennett D. Elzey, Zizheng Dong, Jian-Ting Zhang, Kwangmeyung Kim, Ick Chan Kwon, Kinam Park, Bumsoo Han
Journal: Journal of Controlled Release (2017)
Optimising the Diagnosis of Prostate Cancer in the Era of Multiparametric Magnetic Resonance Imaging: A Cost-effectiveness Analysis Based on the Prostate MR Imaging Study (PROMIS)
Authors: Rita Faria, Marta O. Soares, Eldon Spackman, Hashim U. Ahmed, Louise C. Brown, Richard Kaplan, Mark Emberton, Mark J. Sculpher
Journal: European Urology (2017)

The current recommendation of using transrectal ultrasound-guided biopsy (TRUSB) to diagnose prostate cancer misses clinically significant (CS) cancers. More sensitive biopsies (eg, template prostate mapping biopsy [TPMB]) are too resource intensive for routine use, and there is little evidence on multiparametric magnetic resonance imaging (MPMRI).To identify the most effective and cost-effective way of using these tests to detect CS prostate cancer.Cost-effectiveness modelling of health outcomes and costs of men referred to secondary care with a suspicion of prostate cancer prior to any biopsy in the UK National Health Service using information from the diagnostic Prostate MR Imaging Study (PROMIS).Combinations of MPMRI, TRUSB, and TPMB, using different definitions and diagnostic cut-offs for CS cancer.Strategies that detect the most CS cancers given testing costs, and incremental cost-effectiveness ratios (ICERs) in quality-adjusted life years (QALYs) given long-term costs.The use of MPMRI first and then up to two MRI-targeted TRUSBs detects more CS cancers per pound spent than a strategy using TRUSB first (sensitivity = 0.95 [95% confidence interval {CI} 0.92-0.98] vs 0.91 [95% CI 0.86-0.94]) and is cost effective (ICER = £7,076 [€8350/QALY gained]). The limitations stem from the evidence base in the accuracy of MRI-targeted biopsy and the long-term outcomes of men with CS prostate cancer.An MPMRI-first strategy is effective and cost effective for the diagnosis of CS prostate cancer. These findings are sensitive to the test costs, sensitivity of MRI-targeted TRUSB, and long-term outcomes of men with cancer, which warrant more empirical research. This analysis can inform the development of clinical guidelines.We found that, under certain assumptions, the use of multiparametric magnetic resonance imaging first and then up to two transrectal ultrasound-guided biopsy is better than the current clinical standard and is good value for money.
SP0111 Inhibiting bone formation in the clinic. are we there yet?
Authors: R Landewe
Journal: Annals of the Rheumatic Diseases (2017)

One of the most characteristic features of axial spondyloarthritis (axSpA) is bone formation in the spine (syndesmophytes). Syndesmophytes may occur at any time during the course of the disease, are more frequent in patients with radiographic axSpA (AS) than in those with non-radiographic axSpA, and are best seen on conventional X-rays of the spine. Currently, it is suggested that (low-radiation) CT-scanning of the spine provides a better (more sensitive) picture of developing syndesmophytes than conventional X-rays. Syndesmophytes matter in that they interfere with spinal mobility and physical function independent of inflammation. As such, it makes sens to try and prevent their occurrence or to inhibit their progression. It is a matter of debate whether current available treatments are able to inhibit syndesmophyte growth or occurrence. Part of the debate is the methodological challenges related to measuring syndesmophyte progression properly. In this lecture I will address current issues related to inhibition of syndesmophyte formation in patients with axial SpA. <h3>Disclosure of Interest</h3> None declared
Time from prior chemotherapy (TFPC) as a prognostic factor in advanced urothelial carcinoma (UC) receiving second-line systemic therapy.
Authors: Gregory Russell Pond, Guru Sonpavde, Toni K. Choueiri, Angela Q. Qu, David J. Vaughn, Ronan Fougeray, Guenter Niegisch, Peter Albers, Yu-Ning Wong, Yoo-Joung Ko, Srikala S. Sridhar, Matt D. Galsky, Daniel Peter Petrylak, Tomasz M. Beer, Walter Michael Stadler, Peter H. O'Donnell, Cora N. Sternberg, Jonathan E. Rosenberg, Joaquim Bellmunt Molins
Journal: Journal of Clinical Oncology (2012)

4522 Background: Prognostic factors for overall survival (OS) in patients receiving second-line chemotherapy for advanced platinum-pretreated UC include ECOG performance status (PS) &gt;0, hemoglobin (Hb) &lt;10g/dL and the presence of liver metastasis (LM) (Bellmunt J, J Clin Oncol 2010). We hypothesized that time from prior chemotherapy (TFPC) independently impacts OS. Methods: Of 11 available phase II trials evaluating second-line therapy for advanced UC (n=698), 6 trials with available baseline Hb, PS and LM were utilized (n=534). The trials evaluated vinflunine (2 trials), docetaxel plus vandetanib or placebo, paclitaxel-gemcitabine, nanoparticle-albumin-bound paclitaxel and paclitaxel-cetuximab. The Kaplan-Meier method was used to estimate OS from date of starting second-line therapy. Cox proportional hazards regression stratified for trial was used to evaluate the prognostic effect of factors on OS. TFPC was evaluated as a continuous variable, and based on cutpoints of 3, 6, 9 and 12 months (mo) from prior chemotherapy to first study treatment. The choice of optimal cutpoint for TFPC was determined by the maximum likelihood ratio χ 2 statistic. Results: Overall, 513 patients were evaluable. 64.1% received prior chemotherapy for metastatic disease. Median OS was 6.8 mo (95% CI: 6.1 to 7.4); range was 0 to 84.2 mo. Median OS was 5.2, 7.1, 8.8, 7.6 and 10.6 mo respectively for TFPC &lt;3 (n=181), 3 to &lt;6 (n=133), 6 to &lt;9 (n=77), 9 to &lt;12 (n=45) and &gt;12 (n=77) mo, respectively. Shorter TFPC was independently prognostic for decreased survival. The optimal cutpoint for TFPC was &lt;3 mo, but no well-defined plateau was observed. PS&gt;0 (HR=1.72, p&lt;0.001), LM (HR=1.41, p=0.002), Hb &lt;10 g/dl (HR=1.59, p=0.001) and TFPC &lt;3 mo (HR=1.67, p&lt;0.001) were significantly prognostic in the multivariate model. Timing of prior chemotherapy (metastatic disease vs. perioperative) was not prognostic. Conclusions: A shorter duration of TFPC exhibited a significant negative prognostic impact on OS independent of known prognostic factors in patients receiving second-line therapy for advanced UC. If externally validated, TFPC should be a stratification factor in trials of second-line therapy for advanced UC.
Association of Cigarette Price Differentials With Infant Mortality in 23 European Union Countries
Authors: Filippos T. Filippidis, Anthony A. Laverty, Thomas Hone, Jasper V. Been, Christopher Millett
Journal: JAMA Pediatrics (2017)

Raising the price of cigarettes by increasing taxation has been associated with improved perinatal and child health outcomes. Transnational tobacco companies have sought to undermine tobacco tax policy by adopting pricing strategies that maintain the availability of budget cigarettes.To assess associations between median cigarette prices, cigarette price differentials, and infant mortality across the European Union.A longitudinal, ecological study was conducted from January 1, 2004, to December 31, 2014, of infant populations in 23 countries (comprising 276 subnational regions) within the European Union.Median cigarette prices and the differential between these and minimum cigarette prices were obtained from Euromonitor International. Pricing differentials were calculated as the proportions (%) obtained by dividing the difference between median and minimum cigarette price by median price. Prices were adjusted for inflation.Annual infant mortality rates. Associations were assessed using linear fixed-effect panel regression models adjusted for smoke-free policies, gross domestic product, unemployment rate, education, maternal age, and underlining temporal trends.Among the 53 704 641 live births during the study period, an increase of €1 (US $1.18) per pack in the median cigarette price was associated with a decline of 0.23 deaths per 1000 live births in the same year (95% CI, -0.37 to -0.09) and a decline of 0.16 deaths per 1000 live births the following year (95% CI, -0.30 to -0.03). An increase of 10% in the price differential between median-priced and minimum-priced cigarettes was associated with an increase of 0.07 deaths per 1000 live births (95% CI, 0.01-0.13) the following year. Cigarette price increases across 23 European countries between 2004 and 2014 were associated with 9208 (95% CI, 8601-9814) fewer infant deaths; 3195 (95% CI, 3017-3372) infant deaths could have been avoided had there been no cost differential between the median-priced and minimum-priced cigarettes during this period.Higher cigarette prices were associated with reduced infant mortality, while increased cigarette price differentials were associated with higher infant mortality in the European Union. Combined with other evidence, this research suggests that legislators should implement tobacco tax and price control measures that eliminate budget cigarettes.