tbuckley/cabot-search huggingface dataset:
Back pain in psoriatic arthritis: defining prevalence, characteristics and performance of inflammatory back pain criteria in psoriatic arthritis
Authors: Kristy S Yap, Justine Y Ye, Suzanne Li, Dafna D Gladman, Vinod Chandran
Journal: Annals of the Rheumatic Diseases (2018)

Objective We aimed to determine the agreement between rheumatologist-judged inflammatory back pain (IBP) and criteria defining IBP in patients with psoriatic arthritis (PsA) and predictive value of IBP in identifying axial involvement in PsA. Methods Using prospectively collected data, we investigated the agreement between rheumatologist judgement of IBP and IBP criteria (Calin, Rudwaleit and Assessment of Spondyloarthritis International Society) using the kappa coefficient. We also determined the sensitivity, specificity and likelihood ratios of the presence of back pain, rheumatologist-judged IBP and the three IBP criteria for detecting axial PsA (AxPsA). Finally, we compared the clinical and genetic markers in patients with PsA with axial radiological changes with and without back pain. Results 171 patients (52% male, mean age 46.6 years) were identified. Ninety-six (56.13%) patients reported chronic back pain. Sixty-five (38.01%) had IBP. 54 (32%) patients had evidence of radiological change in the spine. The agreement between rheumatologist judgement of IBP and IBP criteria was highest for the Calin criteria (0.70). Positive likelihood ratio for the presence of radiological axial involvement was highest for Rudwaleit criteria (2.17). No differences between patients with AxPsA with or without back pain were found, except for higher Bath Ankylosing Spondylitis Disease Activity Index and lower prevalence of human leucocyte antigen-B*38 in those with back pain. Conclusion Rheumatologist-judged IBP or the criteria for IBP developed for ankylosing spondylitis may not perform well when ascertaining axial involvement in PsA.
Sodium-Glucose Cotransporter 2 Inhibitors and the Risk of Amputation
Authors: Michael Fralick, Elisabetta Patorno, Michael A. Fischer
Journal: JAMA Internal Medicine (2018)

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Impact of hidradenitis suppurativa on work loss, indirect costs and income
Authors: T. Tzellos, H. Yang, F. Mu, B. Calimlim, J. Signorovitch
Journal: British Journal of Dermatology (2018)

Hidradenitis suppurativa (HS), a chronic cutaneous disease, can negatively affect work life. This retrospective cohort study evaluates the indirect burden among employed patients with HS in the U.S.A. Newly diagnosed and general patients with HS, who were employees (age 18–64 years) from a large claims database (Q1 1999 to Q1 2015), were matched 1 : 5 to controls. Income growth and risk of leaving the workforce were assessed among the newly diagnosed HS and control cohorts in the 5‐year study period. Income, work loss days and indirect costs (absenteeism and disability) were assessed among the general HS and control cohorts in the 1‐year study period. Newly diagnosed (n = 1003, mean age 39·5 years, 66·3% female) and general patients with HS (n = 1204, mean age 39·9 years, 69·1% female) were matched to 5015 and 6020 controls, respectively. Newly diagnosed patients with HS had significantly slower income growth ($324 per year) and higher risk of leaving the workforce (adjusted hazard ratio 1·65, 95% confidence interval 1·45–1·88) compared with controls (all P < 0·05). General patients with HS had more total days of work loss (18·4 vs. 7·7), higher annual total indirect costs ($2925 vs. $1483) and lower annual income ($54 925 vs. $62 357) than controls (all P < 0·001). Patients with newly diagnosed HS and general patients with HS experienced a greater indirect burden than matched controls.
Stenosis Enhances Role of Platelets in Growth of Regional Thrombus and Intimal Wall Thickening in Rat Carotid Arteries
Authors: TakehiroIgawa, YoshieNagamura, YasushiOzeki, HidekiItoh, FumikoUnemi
Journal: Circulation Research (1995)

Abstract The authors present the results of a study in which stenosis was induced, resulting in either thrombus or intimal wall thickening, in rat carotid arteries. At ≥75% stenosis in mildly denuded arteries, an acute and occlusive thrombus formation was induced, but the thrombus was significantly reduced in thrombocytopenia. Thrombus formation near the site of stenosis decreased with decreasing degree of stenosis, whereas the percent formation in the distal region (percent total thrombus) increased. Numerous mural platelet microthrombi were noted at the distal region of the stenosed arteries. After chronic 50% stenosis of the carotid artery for 2 weeks, significant intimal thickening was observed, without any occlusive thrombus formation. The combination with mild denudation was critical in eliciting the effect of stenosis. The magnitude of intimal growth in the stenosed artery was marked by day 6 and plateaued thereafter, whereas it was slight in nonstenosed arteries. The 5-bromodeoxyuridine index of t...
Abstract 17472: Association of Recurrence During Blanking Period With Poor Left Atrial Reverse Remodeling After Initial Catheter Ablation of Non-paroxysmal Atrial Fibrillation: Their Impact on the Clinical Outcome
Authors: Takafumi Oka, Koichi Inoue, Koji Tanaka, Yuko Toyoshima, Nobuaki Tanaka, Masato Okada, Yasushi Koyama, Atsunori Okamura, Katsuomi Iwakura, Kenshi Fujii
Journal: Circulation (2015)

Background: Left atrial reverse remodeling (LARR) after catheter ablation (CA) to atrial fibrillation (AF) indicates reduction of AF substrates in left atrium (LA). In this study, we investigated the impact of LARR on the outcome after CA of non-paroxysmal AF (non-PAF; persistent AF and long-standing persistent AF) and determined the predictor of LARR. Methods and Results: Consecutive 303 patients who underwent initial CA of non-PAF in our institute were retrospectively analyzed. We performed multi-detector computed tomography (MDCT) to evaluate LA end-systolic volume (LAESV) before and 90 days after CA. We determined LARR using %LA reduction [defined as (pre LAESV - post LAESV) / pre LAESV x100]. The average %LA reduction was 20.2±16.8% (median 22.2%). Then we divided them into LARR group (%LA reduction &gt;20%, N=167) and non-LARR group (%LA reduction&lt;20%, N=136). We followed them for 630±153 days to observe their recurrence rate after 90 days blanking period (BP). The recurrence was less frequently observed in LARR group than non-LARR (31.1% vs 56.4%, p&lt;0.01, log-rank test). Next, we examined the predictor of LARR. In univariate analysis, there were no significant differences in age, sex, CHADS2 score, AF duration before CA, anti-arrhythmic drug administration after CA, CA procedure, echocardiographic data and MDCT parameters. Only the recurrence rate during BP was significantly smaller in LARR than non-LARR (43% vs 61%, p=0.002). Then, we divided BP into three parts, early BP, mid BP and late BP (within 7 days, 8 to 30 days, and 31 to 90 days after CA, respectively). The recurrence rate in LARR group was lower than in non-LARR during early BP (27.5% vs 36.8%, p=0.09), mid BP (30.5% vs 42.6%, p=0.03), and late BP (9.0% vs 31.6%, p&lt;0.01). In multivariable analysis, recurrence in late BP revealed to be the predictor of LARR (odds ratio 0.19, [95% confidence interval: 0.10-0.37]). Conclusions: The LARR was associated with better clinical outcome. The absence of recurrence during late BP (31-90 days after CA) was the strong predictor of LARR. These parameters can be acquired at the time point of 3 months after CA and they may be useful for predicting the CA results. Recurrence during late BP might be one of the causes of the poor LARR after CA for non-PAF.
Oxidative Stress Mediates Tumor Necrosis Factor-α–Induced Mitochondrial DNA Damage and Dysfunction in Cardiac Myocytes
Authors: NobuhiroSuematsu, HiroyukiTsutsui, JingWen, DongchonKang, MasakiIkeuchi, TomomiIde, ShunjiHayashidani, TetsuyaShiomi, ToruKubota, NaotakaHamasaki, AkiraTakeshita
Journal: Circulation (2003)

Background— Tumor necrosis factor-α (TNF-α) and angiotensin II (Ang II) are implicated in the development and further progression of heart failure, which might be, at least in part, mediated by the production of reactive oxygen species (ROS). However, the cause and consequences of this agonist-mediated ROS production in cardiac myocytes have not been well defined. Recently, we demonstrated that increased ROS production was associated with mitochondrial DNA (mtDNA) damage and dysfunction in failing hearts. We thus investigated whether the direct exposure of cardiac myocytes to TNF-α and Ang II in vitro could induce mtDNA damage via production of ROS. Methods and Results— TNF-α increased ROS production within cultured neonatal rat ventricular myocytes after 1 hour, as assessed by 2′,7′-dichlorofluorescin diacetate fluorescence microscopy. TNF-α also decreased mtDNA copy number by Southern blot analysis in association with complex III activity, which was prevented in the presence of the antioxidant α-tocophe...
Perceived Mental Stress and Mortality From Cardiovascular Disease Among Japanese Men and Women
Authors: HiroyasuIso, ChigusaDate, AkioYamamoto, HideakiToyoshima, NaohitoTanabe, ShogoKikuchi, TakaakiKondo, YoshiyukiWatanabe, YasuhikoWada, TeruoIshibashi, HiroshiSuzuki, AkioKoizumi, YutakaInaba, AkikoTamakoshi, YoshiyukiOhno
Journal: Circulation (2002)

Background— Perceived mental stress has been associated with risk of coronary heart disease (CHD) in white men, but no prospective data are available for other ethnic groups. Methods and Results— From 1988 to 1990, a total of 73 424 Japanese (30 180 men and 43 244 women), aged 40 to 79 years, without a history of stroke, CHD, or cancer completed a lifestyle questionnaire including perception of mental stress under the Japan Collaborative Cohort Study for Evaluation of Cancer Risk Sponsored by Monbusho (JACC Study). Systematic surveillance was completed until the end of 1997, with a 580 378 person-year follow-up, and the underlying causes of death were determined according to the International Classification of Diseases, 10th revision. For women, there were 316 with total stroke, 113 with CHD, and 643 with total cardiovascular disease (CVD); for men, there were 341, 168, and 778, respectively. Women who reported high stress had a 2-fold higher age-adjusted risk of mortality from total stroke and CHD and 1....
Atrial fibrillation is rare in a contemporary, preindustrial non-Western, non-industrialized population with high inflammation and enlarged left atria
Authors: C. Rowan, A. Achrekar, Bret Alexander Beheim, J. Stieglitz, B. Trumble, H. Kaplan, M. Gurven, K. Tolstrup
Journal: The Lancet (2017)
Abstract 2259: Prostate cancer molecular subtype impacts interpretation of clinical parameters
Authors: Deli Liu
Journal: Cancer Research (2018)

Abstract Background: Molecular characterization of prostate cancer has revealed distinct subtypes with underlying genomic alterations. One of these core subtypes (SPOP mutant prostate cancer) has previously only been identifiable through DNA sequencing, making the impact on prognosis and routinely utilized risk stratification parameters unclear. We aimed to identify prostate cancer molecular subtypes from transcriptional data alone and determine associations with clinicopathologic outcomes and long-term prognosis. Methods: We developed a novel gene expression signature, classifier (SCaPT), and decision tree to predict SPOP mutant subclass from RNA gene expression data and classify common prostate cancer molecular subtypes. We then validated and further interrogated the association of prostate cancer molecular subtypes with pathologic and clinical outcomes in retrospective and prospective cohorts of 8,158 patients. Associations with clinicopathologic variables, metastasis-free and prostate cancer-specific survival were the main outcomes. Findings: The SCaPT model prediction showed high sensitivity and specificity in multiple cohorts across both RNA-seq and microarray gene expression platforms. We predicted 8~9% of cases to be SPOP mutant from both retrospective and prospective cohorts. Surprisingly, we found routine clinical risk factors were disconjugate when molecular subtype was considered. The SPOP mutant subclass was associated with lower frequency of positive margins, extraprostatic extension, and seminal vesicle invasion at prostatectomy. However, SPOP mutant cancers were associated with higher pretreatment serum prostate-specific antigen (PSA). The association between SPOP mutant status and higher PSA level was validated in three independent cohorts. Despite high pre-treatment PSA, the SPOP mutant subtype was associated with a favorable prognosis with improved metastasis-free survival, particularly in patients with “high-risk” preoperative PSA levels. Interpretation: Using a novel gene expression signature to assign the SPOP mutant subclass and a decision tree algorithm to define prostate cancer molecular subclasses, we found the SPOP mutant subclass associated with higher preoperative PSA, less adverse pathological features, and favorable prognosis. These findings suggest a paradigm where interpretation of common risk stratification parameters, particularly PSA, must be modified to account for the molecular subtype of prostate cancer. Citation Format: Deli Liu. Prostate cancer molecular subtype impacts interpretation of clinical parameters [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2259.
Abstract 2700: Specific cell populations from the primary tumor invasive front and lymph nodes show protein signatures associated with local metastasis in head and neck cancer
Authors: Ariane F. Busso-Lopes, César Rivera, Carolina C. Macedo, Barbara P. Mello, Luisa L. Villa, Wilfredo A. González-Arriagada, Adriana F. Paes Leme
Journal: Cancer Research (2018)

Abstract Lymph node metastasis is the main prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC), but no molecular markers are currently used in clinical practice. Considering that the invasive front (IF) of the tumor has a prognostic value due to the invasive and metastatic potential of the cells, we explored the mechanisms associated with lymph node metastasis in the primary tumor IF and its paired lymph nodes from HNSCC patients. For that, the proteomic profile was determined for formalin-fixed, paraffin-embedded (FFPE) tissues using mass spectrometry in a 29-patient cohort. Specific cell populations from primary tumor IF (tumor and stroma cells) and lymph nodes (microenvironment cells) were microdissected and HPV genotyping was performed. In total, 27.5% of the cases were positive for HPV16 and 2,154 ± 285 proteins were identified for the three cell populations analyzed. Eighty-one proteins from tumor cells, 36 proteins of stroma cells and 149 proteins of lymph node microenvironment cells were differentially expressed between HNSCC patients positive and negative for lymph node metastasis (Student´s t-test; P-value ≤ 0.05). Specific processes were enriched for the differentially expressed proteins from tumor, stroma and lymph node cells, including post-translational modification, splicing and translation, respectively. Interestingly, differential proteins isolated from primary tumor cells are mainly transported by exosomes. Therefore, our data provide protein signatures related to lymph node metastasis that are expressed by specific cell populations and candidates as prognostic markers in HNSCC. Financial support: FAPESP (Process number 2015/19191-6). Citation Format: Ariane F. Busso-Lopes, César Rivera, Carolina C. Macedo, Barbara P. Mello, Luisa L. Villa, Wilfredo A. González-Arriagada, Adriana F. Paes Leme. Specific cell populations from the primary tumor invasive front and lymph nodes show protein signatures associated with local metastasis in head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2700.
Abstract 12183: Strain Dispersion is an Early Subclinical Manifestation of Diabetic Cardiomyopathy Assessed by 3D Echocardiography
Authors: RossUpton, EylemLevelt, JamesGamble, KieranClarke, TimBetts, StefanNeubauer, PaulLeeson
Journal: Circulation (2014)

Introduction: The risk of heart failure is increased in patients with type 2 diabetes mellitus (type 2 DM) independently of risk factors such as coronary artery disease. The causes of diabetic cardiomyopathy are multifactorial and not fully elucidated. 3D echocardiography deformation imaging provides a non-invasive assessment of the structure and function of the left ventricle (LV) and has been shown to improve risk evaluation in patients with congestive cardiac failure (CCF). Objective: The aim of this study was to assess the earliest subclinical manifestations of diabetic cardiomyopathy using deformation imaging. Method: 20 patients (mean age 58.6±1.8) with early-onset, uncomplicated type 2 DM, 20 healthy volunteers (mean age 53.3±2.8) and 10 patients with advanced CCF (NYHA class III+IV) (mean age 69.2±3.0) were studied. Strain dispersion was assessed by calculating the standard deviation of time to peak longitudinal strain across 16 segments of the LV. Results: Diabetic patients were matched with the ...
Role of Angiotensin II–Regulated Apoptosis Through Distinct AT1 and AT2 Receptors in Neointimal Formation
Authors: JunSuzuki, MasaruIwai, HironoriNakagami, LanWu, RuiChen, TakashiSugaya, MareomiHamada, KunioHiwada, MasatsuguHoriuchi
Journal: Circulation (2002)

Background— In vitro studies suggest that angiotensin II type 1 and type 2 (AT1 and AT2) receptors exert opposite effects in terms of vasoconstriction, natriuresis, and cell growth, but the role of these receptors in cardiovascular remodeling in vivo is still an enigma. In this study, we tested the hypothesis that AT2 exerts an antiproliferative effect by inducing apoptosis, thereby antagonizing AT1a in vascular remodeling. Methods and Results— Vascular injury was induced by polyethylene cuff placement around the left femoral artery of AT1a-null (AT1aKO), AT2-null (AT2KO), and wild-type mice. Neointimal formation as well as DNA synthesis in vascular smooth muscle cells (VSMC) after vascular injury was exaggerated in AT2KO mice, but they were both suppressed in AT1aKO mice compared with those in wild-type mice. In contrast, the number of apoptotic cells in the injured artery in VSMC was significantly increased in AT1aKO mice but decreased in AT2KO mice. Reverse transcriptase–polymerase chain reaction analy...
Abstract LB-191: BET inhibitors kill colorectal cancer cells by activating death receptor 5 through the ER stress response pathway
Authors: Xiao Tan, Jingshan Tong, Jian Yu, Liangfang Shen, Lin Zhang
Journal: Cancer Research (2018)

Abstract Bromodomain and extra-terminal (BET) family proteins are epigenetic "readers" that are frequently activated in cancer and play an important role in regulating gene expression and oncogenic signaling. Targeting BET proteins using small-molecule inhibitors represents an attractive therapeutic strategy. Several small-molecule BET inhibitors have shown promises in recent preclinical and clinical studies. However, the mechanisms by which BET inhibitors selectively kill cancer cells are not well understood. In this study, we found that the BET inhibitors JQ1 and I-BET151 induce mRNA and protein expression of Death Receptor 5 (DR5) in a variety of colorectal cancer (CRC) cells with different genetic backgrounds. This is an on-target effect as knockdown of the BET family member BRD4 also induces DR5 expression. The induction of DR5 by the BET inhibitors is mediated by C/EBP homologous protein (CHOP) through the endoplasmic reticulum (ER) stress response pathway. Furthermore, knockout of DR5 in colon cancer cells suppresses apoptosis and caspase activation induced by the BET inhibitors, and abrogates their chemosensitization effects in CRC cells. Collectively, our results uncover a key role of DR5 in apoptosis induced by the BET inhibitors in CRC cells, and suggest activation of the death receptor pathway as a novel anticancer mechanism of BET-targeting agents. Citation Format: Xiao Tan, Jingshan Tong, Jian Yu, Liangfang Shen, Lin Zhang. BET inhibitors kill colorectal cancer cells by activating death receptor 5 through the ER stress response pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-191.