tbuckley/cabot-search huggingface dataset:
AB0237 Analysis of the impact of concomitant use of corticosteroids on the clinical outcomes of patients with long-term rheumatoid arthritis in different treatments
Authors: M.J. Carmo, M.M. Pereira, M.D.S. Mastella, I.M.S. Vale, E. Pereira, M.K. Schmitz, S.C.D.M.S. Fialho, G.R.W.D. Castro, I.A. Pereira
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To analyse the impact of the concomitant use of corticosteroids on the treatment of patients with long-term rheumatoid arthritis in different clinical outcomes. <h3>Methods</h3> A cross-sectional study was carried out in a sample of 100 patients with rheumatoid arthritis attended at specialised centres in rheumatology in Florianópolis. Validated instruments were used to evaluate the disease activity (DAS-28 VHS, DAS-28 PCR, SDAI and CDAI), functional ability (HAQ-DI) and quality of life (SF-12 and SF-6D). Statistical analysis was performed using qui-square test (Pearson), Fisher's exact test, Student's t-test, seeking to study the association between the independent variables and the use of corticosteroids. <h3>Results</h3> The mean disease duration of the patients was 15.1±8.7 years, which of, 25% used corticosteroids, with an average dose of 6.7±3.9 mg/day. The mean of the physical component summary (PCS) of SF-12 increased significantly by 1.87 points (47.72±3.23 vs 45.85±2.52 p=0.013) in patients who used corticosteroids, on the other hand, in the mental component summary (MCS) we observed a reduction of the mean by 1.5 points (57.91±3.68 vs 56.41±2.98 p=0.046) in these patients. In the association between the use of corticosteroids with ICADs, HAQ and SF-6D no differences were found independent of the synthetic and/or biological DMARD used. <h3>Conclusions</h3> Use of corticosteroids in different treatment strategies is not associated with an increase in the frequency of clinical remission in patients with rheumatoid arthritis. In patients using corticosteroids there was a better quality of life evaluated by the PCS, but not by the MCS. <h3>Disclosure of Interest</h3> None declared
The Association of Firearm Caliber With Likelihood of Death From Gunshot Injury in Criminal Assaults
Authors: Anthony A. Braga, Philip J. Cook
Journal: JAMA Network Open (2018)

<h3>Importance</h3> A foundational issue in firearms policy has been whether the type of weapon used in an assault affects the likelihood of death. <h3>Objective</h3> To determine whether the likelihood of death from gunshot wounds inflicted in criminal assaults is associated with the power of the assailant's firearm as indicated by its caliber. <h3>Design, Setting, and Participants</h3> Cross-sectional study with multivariate analysis of data on shooting cases extracted by the authors from police investigation files for assaults that took place in Boston, Massachusetts, between January 1, 2010, and December 31, 2014. These data were analyzed between October 1, 2017, and February 18, 2018. In all cases the victim sustained 1 or more gunshot wounds in circumstances that the Boston Police Department deemed criminal. The working sample included all 221 gun homicides and a stratified random sample of 300 nonfatal cases drawn from the 1012 that occurred during the 5-year period. Seven nonfatal cases were omitted because they had been misclassified. <h3>Exposures</h3> The primary source of variation was the caliber of the firearm used to shoot the victim. <h3>Main Outcomes and Measures</h3> Whether the victim died from the gunshot wound(s). <h3>Results</h3> The final sample of 511 gunshot victims and survivors (n = 220 fatal; n = 291 nonfatal) was predominantly male (n = 470 [92.2%]), black (n = 413 [80.8%]) or Hispanic (n = 69 [13.5%]), and young (mean [SD] age, 26.8 [9.4] years). Police investigations determined firearm caliber in 184 nonfatal cases (63.2%) and 183 fatal cases (83.2%). These 367 cases were divided into 3 groups by caliber: small (.22, .25, and .32), medium (.38, .380, and 9 mm), or large (.357 magnum, .40, .44 magnum, .45, 10 mm, and 7.62 × 39 mm). Firearm caliber had no systematic association with the number of wounds, the location of wounds, circumstances of the assault, or victim characteristics, as demonstrated by χ<sup>2</sup>tests of each cluster of variables and by a comprehensive multinomial logit analysis. A logit analysis of the likelihood of death found that compared with small-caliber cases, medium caliber had an odds ratio of 2.25 (95% CI, 1.37-3.70;<i>P</i> = .001) and large caliber had an odds ratio of 4.54 (95% CI, 2.37-8.70;<i>P</i> &lt; .001). Based on a simulation using the logit equation, replacing the medium- and large-caliber guns with small-caliber guns would have reduced gun homicides by 39.5%. <h3>Conclusions and Relevance</h3> Firearms caliber was associated with the likelihood of death from gunshot wounds in criminal assault. Shootings with larger-caliber handguns were more deadly but no more sustained or accurate than shootings with smaller-caliber handguns. This conclusion is of direct relevance to the design of gun policy.
Immunomodulatory interventions in myocardial infarction and heart failure: a systematic review of clinical trials and meta-analysis of IL-1 inhibition
Authors: Mona Panahi, Angelos Papanikolaou, Azam Torabi, Ji-Gang Zhang, Habib Khan, Ali Vazir, Muneer G Hasham, John G F Cleland, Nadia A Rosenthal, Sian E Harding, Susanne Sattler
Journal: Cardiovascular Research (2018)

Following a myocardial infarction (MI), the immune system helps to repair ischaemic damage and restore tissue integrity, but excessive inflammation has been implicated in adverse cardiac remodelling and development towards heart failure (HF). Pre-clinical studies suggest that timely resolution of inflammation may help prevent HF development and progression. Therapeutic attempts to prevent excessive post-MI inflammation in patients have included pharmacological interventions ranging from broad immunosuppression to immunomodulatory approaches targeting specific cell types or factors with the aim to maintain beneficial aspects of the early post-MI immune response. These include the blockade of early initiators of inflammation including reactive oxygen species and complement, inhibition of mast cell degranulation and leucocyte infiltration, blockade of inflammatory cytokines, and inhibition of adaptive B and T-lymphocytes. Herein, we provide a systematic review on post-MI immunomodulation trials and a meta-analysis of studies targeting the inflammatory cytokine Interleukin-1. Despite an enormous effort into a significant number of clinical trials on a variety of targets, a striking heterogeneity in study population, timing and type of treatment, and highly variable endpoints limits the possibility for meaningful meta-analyses. To conclude, we highlight critical considerations for future studies including (i) the therapeutic window of opportunity, (ii) immunological effects of routine post-MI medication, (iii) stratification of the highly diverse post-MI patient population, (iv) the potential benefits of combining immunomodulatory with regenerative therapies, and at last (v) the potential side effects of immunotherapies.
Involvement of iNOS and HIF-1α in the anti-cancer activity of α-phenyl-N-tert-butyl nitrone (PBN) in liver tumor cells
Authors: Wei-Xing Guo, Steven Foster, Quentin Pye, Kenneth Hensley, Charles Stewart, Robert Broyles, Robert Floyd
Journal: Cancer Research (2007)

4838  Our previous studies have shown that PBN, a prototypical nitrone, has anti-cancer activity in the development of choline deficiency (CD)-induced hepatocellular carcinoma in a rat model by shifting the equilibrium from neoplasia to apoptosis and the inhibition of nitric oxide (NO) formation may be involved in its anti-cancer activity. Although a variety of approaches have attempted to reveal the mechanisms of PBN inhibition of tumor development, the exact mechanism remains elusive. In present results, we explored the effect of PBN on the combined cytokines (INF-γ, TNF-α and IL-1β)-induced apoptosis, particularly on the expression of iNOS and HIF-1α in liver tumor cell lines, Hepa 1-6 and Hepa 1C1C7. First we tested the ability of hypoxia at various oxygen concentrations as well as anoxia to induce HIF-1α expression in the cell lines and the possible effects of the combined cytokines, on the expression of iNOS and HIF-1α. The results demonstrated that there were dramatic increases in the expression of HIF-1α when the cells were exposed to anoxia and in the expression of iNOS when the cells were exposed to the combined cytokines (ITI). A significant increase in NO production measured as nitrite in the media was also observed. The most important findings were that when PBN was added in culture media, the anoxia-induced expression of HIF-1α and ITI-induced iNOS were inhibited. Additionally, a reduction of ITI-induced NO in the media was observed when the cells exposed to PBN. Furthermore, we tested the effect of PBN on induction of apoptosis measured as DNA fragmentation at G0/G1 phase. An enhanced increase in apoptosis was observed when the cells were exposed to ITI and PBN, particularly under anoxia. Thus, these preliminary results not only confirmed our previous observations in vivo, but also clearly indicated that regulation of iNOS and HIF-1α was involved in the PBN anti-cancer activity. The discovery that PBN inhibits HIF-1α activation suggests that nitrones represent a potential new class of anti-cancer therapeutics. This research is supported in part by NIH RO1CA82506 and OARS AR05.2-041.
Treatment Strategy for Newly Diagnosed T1 High-grade Bladder Urothelial Carcinoma: New Insights and Updated Recommendations
Authors: Zachary Klaassen, Ashish M. Kamat, Wassim Kassouf, Paolo Gontero, Humberto Villavicencio, Joaquim Bellmunt, Bas W.G. van Rhijn, Arndt Hartmann, James W.F. Catto, Girish S. Kulkarni
Journal: European Urology (2018)
Concern Regarding Age Distribution of Breast Cancer
Authors: Kathleen A. Cronin, Donald A. Berry
Journal: JAMA Surgery (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery 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 Surgery journal
Independent risk factors that predict bile leakage after hepatectomy for hepatocellular carcinoma: Cohort study
Authors: Ryosuke Nakano, Masahiro Ohira, Tsuyoshi Kobayashi, Yuki Imaoka, Hiroaki Mashima, Megumi Yamaguchi, Naruhiko Honmyo, Sho Okimoto, Michinori Hamaoka, Seiichi Shimizu, Shintaro Kuroda, Hiroyuki Tahara, Kentaro Ide, Hideki Ohdan
Journal: International Journal of Surgery (2018)
Development of a unique anti-CD137 therapeutic antibody: Efficacy and safety profiles in mono and combination therapy.
Authors: Guizhong Liu, Peter Cheung, Jun Chen, Xiaohong She, Felix Fangyong Du, Peter Luo
Journal: Journal of Clinical Oncology (2017)

e23079 Background: Abstract: CD137 (4-1BB), a member of the TNFR super family, is expressed on several subsets of activated immune cells and acts as co-stimulatory receptor for T-cells to promote cellular proliferation, survival and cytokine production. Agonist antibodies against human CD137 in early clinical trials show strikingly different toxicology profiles, ranging from severe liver toxicity at low doses, to manageable adverse effects at modest doses. Whereas preclinical studies in mouse show intense liver T-cell infiltration and toxicity by surrogate agonist mAb. The preclinical efficacy and pharmacology of anti-CD137 were extensively tested and validated in various tumor models with intact immune system. Since none of the available anti-CD137 agonist antibodies display multiple species cross reactivity including rodent, the translational significance of these mAbs is limited concerning their efficacy and safety profile. Methods: Through our proprietary Dynamic Precision Library (DPL) technology, we have discovered multiple agonistic antibodies that exhibit high affinity and broad species cross-reactivity against a unique epitope shared among human, monkey and rodent CD137. Results: These mAbs, after crosslinking, strongly activate CD137 mediated cellular NFkB signaling, as well as stimulate T-cell proliferation and IFNg release in the presence of suboptimal concentrations of anti-CD3 antibodies. The broad species cross-reactivity by a single therapeutic agent enabled us to evaluate their potentiation of host immune responses that gives rise to the anti-tumor efficacy and potential toxicity in relevant rodent and monkey models. Our lead anti-CD137 agonist mAb has demonstrated robust anti-tumor activities in multiple mouse syngeneic tumor models, with durable antigen specific protective memory T-cell responses. Conclusions: In sharp contrast to surrogate anti-mouse CD137 mAbs, no toxicities including liver inflammation or other adverse effects were observed. These preclinical results warrant further clinical development of our lead as a novel immunotherapeutic anti-cancer agent.
Therapeutic Effects of a <scp>TANK</scp>‐Binding Kinase 1 Inhibitor in Germinal Center–Driven Collagen‐Induced Arthritis
Authors: Cynthia Louis, Devi Ngo, Damian B. D'Silva, Jacinta Hansen, Louisa Phillipson, Helene Jousset, Patrizia Novello, David Segal, Kate E. Lawlor, Christopher J. Burns, Ian P. Wicks
Journal: Arthritis & Rheumatology (2018)

Objective The production of class‐switched high‐affinity autoantibodies derived from organized germinal centers ( GC s) is a hallmark of many autoimmune inflammatory diseases, including rheumatoid arthritis ( RA ). TANK ‐binding kinase 1 ( TBK ‐1) is a serine/threonine kinase involved in the maturation of GC follicular helper T (Tfh) cells downstream of inducible costimulator signaling. We undertook this study to assess the therapeutic potential of TBK ‐1 inhibition using the small‐molecule inhibitor WEHI ‐112 in antibody‐dependent models of inflammatory arthritis. Methods Using the models of collagen‐induced arthritis ( CIA ), antigen‐induced arthritis ( AIA ), and K/BxN serum‐transfer–induced arthritis ( STIA ), we determined the effectiveness of WEHI ‐112 at inhibiting clinical and histologic features of arthritis in C57 BL /6 and DBA /1 mice. We used immunohistochemistry to characterize GC populations during CIA development, and we used enzyme‐linked immunosorbent assays to determine levels of Ig autoantibodies in WEHI ‐112–treated mice compared to vehicle‐treated mice. Results WEHI ‐112, a tool compound that is semiselective for TBK ‐1 but that also has activity against IKK ε and JAK 2, abolished TBK ‐1–dependent activation of interferon ( IFN ) regulatory factor 3 and inhibited type I IFN responses in vitro. In vivo, treatment with WEHI ‐112 selectively abrogated clinical and histologic features of established, antibody‐dependent CIA , but had minimal effects on an antibody‐independent model of AIA or on K/BxN STIA . In keeping with these findings, WEHI ‐112 reduced arthritogenic type II collagen–specific IgG1 and IgG2b antibody production. Furthermore, WEHI ‐112 altered the GC Tfh cell phenotype and GC B cell function in CIA . Conclusion We report that TBK ‐1 inhibition using WEHI ‐112 abrogated antibody‐dependent CIA . As WEHI‐112 failed to inhibit non–antibody‐driven joint inflammation, we conclude that the major effect of this compound was most likely the targeting of TBK ‐1–mediated mechanisms in the GC reaction. This approach may have therapeutic potential in RA and in other GC ‐associated autoantibody‐driven inflammatory diseases.
Smoking and increased breast cancer risk in younger women in Appalachian Kentucky.
Authors: Indraneel Reddy, Anjali Shankar, Priya Mallikarjun, Nicola Jabbour, Mark Dignan
Journal: Journal of Clinical Oncology (2012)

e11097 Background: Smoking rates in Kentucky are among the highest in the US. Data from the Centers for Disease Control and Prevention for 2011 showed that in Kentucky 25.2% of the adult population are current smokers compared to 18.4% nationwide. In addition, smoking rates in the Appalachian region are substantially higher than the state rate. Breast cancer rates are also elevated in Appalachian Kentucky, with data from the Kentucky State Cancer Registry for 2004-2008 showing an incidence rate of 67.3 per 100,000 in Appalachia compared to 65.6 per 100,000 for the state. Our objective was to evaluate the association of smoking and breast cancer among women in Appalachian Kentucky. Methods: We reviewed all the breast cancer data from a large community hospital serving the Appalachian areas of Kentucky. Data were collected from the hospital tumor registry for the period 1996-2005 and included demographic characteristics and smoking status, in addition to information about the breast cancer. No personal identifiers were collected. Breast cancers were coded as invasive or non-invasive and smoking status was coded as current smoker, non-smoker or unknown. Results: Data from records of 392 patients were included in the analyses. Over 90% of the breast cancers in the 392 were invasive. Age at diagnosis ranged from 24 to 92 and the mean was 59.9 years (standard deviation= 13.5. 21.2% of the records indicated a family history of breast cancer. Of the 392 patients, 162 (41.3%) were smokers. Analysis of the data by age at diagnosis showed that of the 120 women diagnosed with breast cancer at age less than 65, 46.5% were smokers, compared to 31.3% of those age 65 or older (p=.005, Fisher’s Exact Test). Conclusions: The risk of breast cancer in women under age 65 appears to be associated with smoking in this population. Additional research is needed to more fully explore this association.
IL1 Receptor Antagonist Controls Transcriptional Signature of Inflammation in Patients with Metastatic Breast Cancer
Authors: Te-Chia Wu, Kangling Xu, Jan Martinek, Robyn R. Young, Romain Banchereau, Joshy George, Jacob Turner, Kyung In Kim, Sandra Zurawski, Xuan Wang, Derek Blankenship, Hannah M. Brookes, Florentina Marches, Gerlinde Obermoser, Elizabeth Lavecchio, Maren K. Levin, Sookyoung Bae, Cheng-Han Chung, Jennifer L. Smith, Alma-Martina Cepika, Kyp L. Oxley, George J. Snipes, Jacques Banchereau, Virginia Pascual, Joyce O'Shaughnessy, A. Karolina Palucka
Journal: Cancer Research (2018)

Abstract Inflammation affects tumor immune surveillance and resistance to therapy. Here, we show that production of IL1β in primary breast cancer tumors is linked with advanced disease and originates from tumor-infiltrating CD11c+ myeloid cells. IL1β production is triggered by cancer cell membrane–derived TGFβ. Neutralizing TGFβ or IL1 receptor prevents breast cancer progression in humanized mouse model. Patients with metastatic HER2− breast cancer display a transcriptional signature of inflammation in the blood leukocytes, which is attenuated after IL1 blockade. When present in primary breast cancer tumors, this signature discriminates patients with poor clinical outcomes in two independent public datasets (TCGA and METABRIC). Significance: IL1β orchestrates tumor-promoting inflammation in breast cancer and can be targeted in patients using an IL1 receptor antagonist. Cancer Res; 78(18); 5243–58. ©2018 AACR. See related commentary by Dinarello, p. 5200
COX-1 mediates IL-33–induced extracellular signal-regulated kinase activation in mast cells: Implications for aspirin sensitivity
Authors: Dingxin Pan, Kathleen M. Buchheit, Sachin K. Samuchiwal, Tao Liu, Haley Cirka, Hannah Raff, Joshua A. Boyce
Journal: Journal of Allergy and Clinical Immunology (2018)
Mapping of Atrial Activation With a Noncontact, Multielectrode Catheter in Dogs
Authors: AlanKadish, JohnHauck, BrianPederson, GraydonBeatty, CharlesGornick
Journal: Circulation (1999)

Background—Endocardial mapping of sustained arrhythmias has traditionally been performed with a roving diagnostic catheter. Although this approach is adequate for many tachyarrhythmias, it has limitations. The purpose of this study was to evaluate a novel noncontact mapping system for assessing atrial tachyarrhythmias. Methods and Results—The mapping system consists of a 9F multielectrode-array balloon catheter that has 64 active electrodes and ring electrodes for emitting a locator signal. The locator signal was used to construct a 3-dimensional right atrial map; it was independently validated and was highly accurate. Virtual electrograms were calculated at 3360 endocardial sites in the right atrium. We evaluated right atrial activation by positioning the balloon catheter in the mid right atrium via a femoral venous approach. Experiments were performed on 12 normal mongrel dogs. The mean correlation coefficient between contact and virtual electrograms was 0.80±0.12 during sinus rhythm. Fifty episodes of ...
Abstract 19023: A Large-Scale, Functional Screening of Mammalian Mechanosensitive Genes Using Drosophila Rnai library- Smarcd3/Bap60 is a Mechanosensitive Pro-Inflammatory Gene
Authors: Sandeep Kumar, In Hwan Jang, Dong Won Kang, Chanwoo Kim, Won Jae Lee, Hanjoong Jo
Journal: Circulation (2016)

Introduction: Atherosclerosis in a chronic inflammatory disease of the arterial wall that preferentially occurs in regions exposed to disturbed blood flow, in part, due to alterations in gene expre...
Renal Tubular Secretion of Digoxin
Authors: Evasteiness
Journal: Circulation (1974)

To study the mechanism of the renal handling of digoxin, simultaneous measurements of digoxin and inulin clearances were performed in 13 digitalized patients with congestive heart disease. The renal digoxin clearances exceeded inulin clearances, indicating an active tubular secretion of digoxin. No evidence of tubular backward diffusion was disclosed. Treatment with spironolactone (Aldactone) decreased the digoxin clearances, suggesting an inhibition of the tubular secretion of digoxin in the distal segment of the renal tubulus. After blocking the tubular secretion, the calculated renal clearances of nonproteinbound digoxin in plasma were similar to that of inulin, suggesting a glomerular filtration of free plasma digoxin. Plasma digoxin level rose during treatment with spironolactone.