tbuckley/cabot-search huggingface dataset:
SAT0425 Symptomology, disease status, and remission rates of non-radiographic axial spondyloarthritis and ankylosing spondylitis patients in europe
Authors: TM Hunter, D Sandoval, S Lobosco, R Moon, J Birt, G Miligan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Axial Spondyloarthritis (axSpA) is a chronic inflammatory disease predominantly affecting the sacroiliac joints and spine. Ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA) have been considered to represent the same axial spondyloarthritis disorder, but are differentiated by the presence or absence of structural changes in the sacroiliac joints as determined by common imaging modalities. <h3>Objectives</h3> To better understand the symptoms and clinical characteristics of nr-axSpA patients and how they compare to ankylosing spondylitis patients in Europe. <h3>Methods</h3> Data drom the 2015 SpA Disease Specific Programme, a cross-sectional, multi-national survey of patients and rheumatologists conducted in France, Germany, Italy, Spain, and the UNited Kingdom were analyzed. Rheumatologists (n=299) completed forms containing patient demographics, clinical results and symptomology. Symptoms, disease activity, and disease status (defined as improving, stable, unstable, deteriorating) of AS and nr-axSpA patients were compared. <h3>Results</h3> A total of 3,033 patients (AS: 1,520; nr-axSpA: 1,513) were included in the analysis. A higher proportion of AS patients were male (72% vs. 53%), older (mean age=44.8 vs. 41.0), had a higher BMI and were employed when compared to nr-axSpA patients. Nr-axSpA patients9 current disease status was less likely to be stable (p&lt;0.0001) in comparison to AS patients. Nr-axSpA patients were also less likely to be in remission (p&lt;0.0001). Nr-axSpA patients were reported as having higher pain level (p=0.0333) than AS patients. AS patients had more axSpA symptoms, such as spinal fusion and loss of movement, however nr-axSpA patients were more likely to have inflammatory back pain, enthesitis, persistent lower back pain, and nocturnal wakening. <h3>Conclusions</h3> Both nr-axSpA and AS appear to have many similar clinical characteristics with few distinct features between them. However, in spite of these similarities, nr-axSpA patients show less stability and a lower likelihood of remission when compared to AS patients. These findings may suggest that nr-axSpA is as burdensome as AS, and that both conditions may warrant similar treatment approaches from an early stage. <h3>Disclosure of Interest</h3> T. Hunter Employee of: Eli Lilly and Company, D. Sandoval Employee of: Eli Lilly and Company, S. Lobosco Employee of: Adelphi Real World, R. Moon Employee of: Adelphi Real World, J. Birt Employee of: Eli Lilly and Company, G. Miligan Employee of: Adelphi Real World
P14 ARF interferes with HPV oncoproteins biological activity in head and neck cancer
Authors: Raul D. Bernabe, Sharon Fonseca Williams, Rafael A. Quintana, Xandra N. Zayas, Maria Marcos-Matinez, Juan Trinidad-Pinedo, Adriana Baez
Journal: Cancer Research (2004)

1862  Alterations in the chromosome 9p21-22 are common in head and neck (HNSCC) cancer. Recent studies demonstrate that Human papillomavirus type 16 (HPV16) infection is the causal agent for a subgroup of HNSCC. More recently it has been shown that HPV16 oncoprotein E7 is inhibited by P19ARF (P14ARF in humans) in a mouse model. In these studies we analyses the expression of p14, p15, p16 in relationship to the oncoprotein E6 and E7. A series of 50 HNSCC samples were analyzed by PCR, RT-PCR immunohistochemistry (IHC), MSP-PCR and single-strand conformational polymorphism assay (PCR-SSCP), We found that 18% were HPV16 positive. Both, p14 (ARF) and p15 (INK4b) were not expressed in 16% of the tumors tested, whereas 18% did not express p16 (INK4a). A high aberrant methylation pattern (50%) of p16 (INK4A) gene was established. The PCR-SSCP analysis detected somatic mutations in 38% of tumors that expressed p14 (ARF), p15 (INK4b) and/or p16 (INK4a). P14 (ARF) and p15 (INK4a) were mutated in five tumors each (5/19; 26%), whereas p16 (INK4b) exon 2 showed a higher percentage of mutations (9/20; 45%). We found that HPV16 positive tumors did not show p14ARF mRNA expression. On the contrary p16 (INK4a) and p15 (INK4b) was not affected by the present of the oncoproteins. Our results suggest that the presence of wild p14ARF might interfere with the biological activity of HPV16 oncoproteins.
フィブリル内珪化コラーゲン足場は単球は細胞ホーミング,血管新生と骨再生を促進する【Powered by NICT】
Authors: Sun Jin-long, Jiao Kai, Niu Li-na, Jiao Yang, Song Qun, Shen Li-juan, R Tay Franklin, Chen Ji-hua
Journal: Biomaterials (2017)
PRC2-Mediated Transcriptomic Alterations at the Embryonic Stage Govern Tumorigenesis and Clinical Outcome in MYCN-Driven Neuroblastoma
Authors: Shoma Tsubota, Satoshi Kishida, Teppei Shimamura, Miki Ohira, Satoshi Yamashita, Dongliang Cao, Shinichi Kiyonari, Toshikazu Ushijima, Kenji Kadomatsu
Journal: Cancer Research (2017)

Pediatric cancers such as neuroblastoma are thought to involve a dysregulation of embryonic development. However, it has been difficult to identify the critical events that trigger tumorigenesis and differentiate them from normal development. In this study, we report the establishment of a spheroid culture method that enriches early-stage tumor cells from TH-MYCN mice, a preclinical model of neuroblastoma. Using this method, we found that tumorigenic cells were evident as early as day E13.5 during embryo development, when the MYC and PRC2 transcriptomes were significantly altered. Ezh2, an essential component of PRC2, was expressed in embryonic and postnatal tumor lesions and physically associated with N-MYC and we observed that H3K27me3 was increased at PRC2 target genes. PRC2 inhibition suppressed in vitro sphere formation, derepressed its target genes, and suppressed in situ tumor growth. In clinical specimens, expression of MYC and PRC2 target genes correlated strongly and predicted survival outcomes. Together, our findings highlighted PRC2-mediated transcriptional control during embryogenesis as a critical step in the development and clinical outcome of neuroblastoma. Cancer Res; 77(19); 5259-71. ©2017 AACR.
The Phosphatidylinositol 3-Kinase Pathway as a Potential Therapeutic Target in Bladder Cancer
Authors: Shu-Xiong Zeng, Yanjun Zhu, Ai-Hong Ma, Weimin Yu, Hongyong Zhang, Tzu-Yin Lin, Wei Shi, Clifford G. Tepper, Paul T. Henderson, Susan Airhart, Jian-Ming Guo, Chuan-Liang Xu, Ralph W. deVere White, Chong-Xian Pan
Journal: Clinical Cancer Research (2017)

Purpose: Activation of the PI3K pathway occurs in over 40% of bladder urothelial cancers. The aim of this study is to determine the therapeutic potential, the underlying action, and the resistance mechanisms of drugs targeting the PI3K pathway.Experimental Design: Urothelial cancer cell lines and patient-derived xenografts (PDXs) were analyzed for alterations of the PI3K pathway and for their sensitivity to the small-molecule inhibitor pictilisib alone and in combination with cisplatin and/or gemcitabine. Potential predictive biomarkers for pictilisib were evaluated, and RNA sequencing was performed to explore drug resistance mechanisms.Results: The bladder cancer cell line TCCSUP, which harbors a PIK3CA E545K mutation, was sensitive to pictilisib compared to cell lines with wild-type PIK3CA Pictilisib exhibited stronger antitumor activity in bladder cancer PDX models with PI3KCA H1047R mutation or amplification than the control PDX model. Pictilisib synergized with cisplatin and/or gemcitabine in vitro, significantly delayed tumor growth, and prolonged survival compared with single-drug treatment in the PDX models. The phosphorylation of ribosomal protein S6 correlated with response to pictilisib both in vitro and in vivo, and could potentially serve as a biomarker to predict response to pictilisib. Pictilisib activated the compensatory MEK/ERK pathway that likely contributed to pictilisib resistance, which was reversed by cotreatment with the RAF inhibitor sorafenib. RNA sequencing of tumors resistant to treatment suggested that LSP1 downregulation correlated with drug resistance.Conclusions: These preclinical results provide new insights into the therapeutic potential of targeting the PI3K pathway for the treatment of bladder cancer. Clin Cancer Res; 23(21); 6580-91. ©2017 AACR.
FRI0235 Analgesic efficacy of tramadol/piroxicam combination: clinical aspects
Authors: K Sekelj-Kauzlaric, B Matanovic, N Kauzlaric, R Cop, S Potrebica
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To evaluate the efficacy and safety of combination analgesic tramadol/piroxicam for the treatment of low back pain. <h3>Methods</h3> This 2- week study took place in two REHA-Centres in Croatia. Patients took medication as needed for the treatment of acute low back pain and/or osteoarthritis pain. They were given 20 mg of piroxicam in the morning and 50 mg of tramadol every 12 h for 15 days. Patients reported maximum pain relief (VAS scale 0 to 10) and rated overall efficacy (scale 1 = poor to 5 = excellent) at the final visit. Adverse events (AEs) were monitored throughout the study. <h3>Results</h3> A total of 70 patients from two REHA-Centres provided data. We present the analysis of age, sex and profession. Most of our patients (61%) were employed. Our patients needed therapy for osteoarthritis pain (52%), low back pain (40%) and other (osteoporosis, RA, SA) 8%. After 15 days combination tramadol/piroxicam provided pain relief (range 2,5 ? 3,5). Overall efficacy of combination was rated 35% ?very good? or ?excellent? by 20%, ?good? by 35% and ?poor? by 10% only. There were no serious or unexpected AEs. The most common AEs were: nausea 20%, constipation 18%, headache 16%, dizziness 12% and somnolence 8%. <h3>Conclusion</h3> This study demonstrated that the combination analgesic tramadol/piroxicam is effective and well tolerated in patients with low back pain and/or ostheoarthritis.
AHA/ACCF/HRS Recommendations for the Standardization and Interpretation of the Electrocardiogram
Authors: Borys Surawicz, Rory Childers, Barbara J. Deal, Leonard S. Gettes
Journal: Circulation (2009)

The American Heart Association, the American College of Cardiology, and the Heart Rhythm Society make every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel.Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived
In type 1 diabetes, education with either insulin pumps or daily injections did not differ for HbA<sub>1c</sub> at 2 y
Authors: Lorraine L. Lipscombe
Journal: Annals of Internal Medicine (2017)

Source Citation REPOSE study group, Heller S, Amiel S, et al. Relative effectiveness of insulin pump treatment over multiple daily injections and structured education during flexible intensive insulin treatment for type 1 diabetes: cluster randomised trial (REPOSE). BMJ. 2017;356:j1285. 28360027
Abstract 382: Reduced Mitochondrial Function and Metabolic Dysregulation in Aneurysmal Fibulin-4 Mice.
Authors: Ingrid van der Pluijm, P.M. van Heijningen, A. IJpma, N. van Vliet, W Sluiter, E.C. Davis, L.J. Ringuette, D.H.W. Dekkers, S. Ghazi, I. Que, E.L. Kaijzel, L. te Riet, S.I.C. Gabriels, P.G. Mastroberardino, R. van der Linden, M. Vermeij, J.A. Demmers, D. Das, H. Yanagisawa, R. Kanaar, J. Essers
Journal: Circulation Research (2015)

Thoracic aortic aneurysms are a life-threatening condition often diagnosed too late. The underlying mechanism is largely unknown. An accurate and early predictive biomarker for aneurysm formation has not yet been identified, although some molecular processes, such as disturbed TGF-β signalling, have been implicated. To discover novel robust biomarkers, we aimed to better understand the molecular mechanisms involved in aneurysm initiation and progression. In Fibulin-4 R/R mice, the extracellular matrix protein Fibulin-4 is 4-fold reduced, resulting in progressive ascending aneurysm formation and early death around 3 months of age. We performed LC-MS/MS proteomics and transcriptomics analyses on the aortas of Fibulin-4 R/R and Fibulin-4 +/+ mice. Protein and gene data sets were separately analysed for genotype specific differences with Ingenuity Pathway analysis tools. Intriguingly, we observed alterations in mitochondrial composition in aortas from Fibulin-4 R/R mice. Consistently, functional studies in Fibulin-4 R/R vascular smooth muscle cells (VSMCs) revealed lower oxygen consumption rates, but increased acidification rates compared to Fibulin-4 +/+ . The mitochondria in VSMCs of Fibulin-4 R/R mice were reduced in size and had increased complex I-IV levels. Furthermore, aortas of aneurysmal Fibulin-4 R/R mice displayed increased levels of ROS. Consistent with these findings, gene expression analyses revealed the dysregulation of metabolic pathways. In accordance, ketone levels in the blood of Fibulin-4 R/R mice were reduced and liver fatty acids were decreased, while liver glycogen was increased. As predicted by these findings, activity of PGC1α, a key regulator between mitochondrial function and organismal metabolism, was downregulated in Fibulin-4 R/R VSMCs. In conclusion, our data indicate altered mitochondrial function and metabolic dysregulation, leading to increased ROS levels and altered energy production, as a novel mechanism, which may contribute to thoracic aortic aneurysm formation. This discovery will not only provide new biomarkers that can be validated in human aortas, but they will also provide the rational for new interventions such as alterations in diet to prevent aneurysm formation.
Degradation of Cystine by Normal Liver But Not by Transplanted Hepatomas
Authors: Jesse P. Greenstein
Journal: JNCI Journal of the National Cancer Institute (1943)

Degradation of Cystine by Normal Liver But Not by Transplanted Hepatomas Jesse P. Greenstein Jesse P. Greenstein senior biochemist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 3, Issue 5, June 1943, Pages 491–494, https://doi.org/10.1093/jnci/3.5.491 Published: 01 June 1943
Association of Childhood Body Mass Index and Change in Body Mass Index With First Adult Ischemic Stroke
Authors: Line K. Gjærde, Michael Gamborg, Lars Ängquist, Thomas C. Truelsen, Thorkild I. A. Sørensen, Jennifer L. Baker
Journal: JAMA Neurology (2017)

<h3>Importance</h3> The incidence of ischemic stroke among young adults is rising and is potentially due to an increase in stroke risk factors occurring at younger ages, such as obesity. <h3>Objectives</h3> To investigate whether childhood body mass index (BMI) and change in BMI are associated with adult ischemic stroke and to assess whether the associations are age dependent or influenced by birth weight. <h3>Design, Setting, and Participants</h3> This investigation was a population-based cohort study of schoolchildren born from 1930 to 1987, with follow-up through national health registers from 1977 to 2012 in Denmark. Participants were 307 677 individuals (8899 ischemic stroke cases) with measured weight and height at ages 7 to 13 years. The dates of the analysis were September 1, 2015, to May 27, 2016. <h3>Main Outcomes and Measures</h3> Childhood BMI, change in BMI, and birth weight. Ischemic stroke events were divided into early (≤55 years) or late (&gt;55 years) age at diagnosis. <h3>Results</h3> The study cohort comprised 307 677 participants (approximately 49% female and 51% male). During the study period, 3529 women and 5370 men experienced an ischemic stroke. At all ages from 7 to 13 years, an above-average BMI<i>z</i>score was positively associated with early ischemic stroke. At age 13 years, a BMI<i>z</i>score of 1 was associated with hazard ratios (HRs) of 1.26 (95% CI, 1.11-1.43) in women and 1.21 (95% CI, 1.10-1.33) in men. No significant associations were found for below-average BMI<i>z</i>scores. Among children with above-average BMI<i>z</i>scores at age 7 years, a score increase of 0.5 from ages 7 to 13 years was positively associated with early ischemic stroke in women (HR, 1.10; 95% CI, 1.01-1.20) and in men (HR, 1.08; 95% CI, 1.00-1.16). Similarly, among children with below-average BMI<i>z</i>scores at age 7 years, a score increase of 0.5 from ages 7 to 13 years was positively associated with early ischemic stroke in women (HR, 1.14; 95% CI, 1.06-1.23) and in men (HR, 1.10; 95% CI, 1.04-1.18). Adjusting for birth weight minimally affected the associations. <h3>Conclusions and Relevance</h3> Independent of birth weight, above-average childhood BMI and increases in BMI during childhood are positively associated with early adult ischemic stroke. To avoid the occurrence of early ischemic stroke associated with childhood overweight and obesity, these results suggest that all children should be helped to attain and maintain healthy weights.
Treatment of Patients With Metastatic Cancer Using a Major Histocompatibility Complex Class II–Restricted T-Cell Receptor Targeting the Cancer Germline Antigen MAGE-A3
Authors: Yong-Chen Lu, Linda L. Parker, Tangying Lu, Zhili Zheng, Mary Ann Toomey, Donald E. White, Xin Yao, Yong F. Li, Paul F. Robbins, Steven A. Feldman, Pierre van der Bruggen, Christopher A. Klebanoff, Stephanie L. Goff, Richard M. Sherry, Udai S. Kammula, James C. Yang, Steven A. Rosenberg
Journal: Journal of Clinical Oncology (2017)

Purpose Adoptive transfer of genetically modified T cells is being explored as a treatment for patients with metastatic cancer. Most current strategies use genes that encode major histocompatibility complex (MHC) class I–restricted T-cell receptors (TCRs) or chimeric antigen receptors to genetically modify CD8 + T cells or bulk T cells for treatment. Here, we evaluated the safety and efficacy of an adoptive CD4 + T-cell therapy using an MHC class II–restricted, HLA-DPB1*0401–restricted TCR that recognized the cancer germline antigen, MAGE-A3 (melanoma-associated antigen-A3). Patients and Methods Patients received a lymphodepleting preparative regimen, followed by adoptive transfer of purified CD4 + T cells, retrovirally transduced with MAGE-A3 TCR plus systemic high-dose IL-2. A cell dose escalation was conducted, starting at 10 7 total cells and escalating at half-log increments to approximately 10 11 cells. Nine patients were treated at the highest dose level (0.78 to 1.23 × 10 11 cells). Results Seventeen patients were treated. During the cell dose-escalation phase, an objective complete response was observed in a patient with metastatic cervical cancer who received 2.7 × 10 9 cells (ongoing at ≥ 29 months). Among nine patients who were treated at the highest dose level, objective partial responses were observed in a patient with esophageal cancer (duration, 4 months), a patient with urothelial cancer (ongoing at ≥ 19 months), and a patient with osteosarcoma (duration, 4 months). Most patients experienced transient fevers and the expected hematologic toxicities from lymphodepletion pretreatment. Two patients experienced transient grade 3 and 4 transaminase elevations. There were no treatment-related deaths. Conclusion These results demonstrate the safety and efficacy of administering autologous CD4 + T cells that are genetically engineered to express an MHC class II–restricted antitumor TCR that targets MAGE-A3. This clinical trial extends the reach of TCR gene therapy for patients with metastatic cancer.
THU0723-HPR A physiotherapy-led in-patient intensive rehabilitation programme for ankylosing spondylitis: follow-up outcomes
Authors: C Clarke, P Taggart, J Monaghan, J McKnight, A Cairns
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Physiotherapy and exercise are highly important in the management of Ankylosing Spondylitis (AS). Physiotherapy is delivered to patients with AS in either in-patient or out-patient settings. Knowledge of the effectiveness of an in-patient delivered programme is useful for physiotherapists in assisting patients to achieve their goals. <h3>Objectives</h3> To assess the short-term effectiveness of an intensive rehabilitation programme using BASMI and EASI-QOL outcomes, and long-term patient satisfaction and physical activity behaviour and adherence to exercise plan. <h3>Methods</h3> Thirty-two AS patients (25 males and 7 females) admitted to an in-patient rheumatology ward underwent a 1 to 2-week physiotherapy-led intensive rehabilitation programme and were then discharged with a home exercise programme. Pre/post rehabilitation BASMI scores were available for 26 patients. The primary outcome measure was the proportion of patients achieving an improvement on BASMI scores at discharge. Secondary outcome measures included improvements in physical activity levels and adherence to home exercise plan for longer than 3 months which was obtained via a postal patient satisfaction and physical activity questionnaire achieving a response rate of 50% (n=16). <h3>Results</h3> Improvements in BASMI scores was achieved in 69% of patients (n=18) at the end of the in-patient rehabilitation period. Improvements in EASI-QOL were achieved in 83% of patients (n=15) at the end of the in-patient rehabilitation period. Ninety- four percent of patients (n=15) increased their physical activity levels after discharge, with 81% (n=13) of patients maintaining their home exercise programme for 3 months or more. Thirty-seven percent (n=7) of patients carry out at least 150 minutes of physical activity per week (National Recommended Physical Activity Guidelines is 150 minutes/week of moderate intensity). <h3>Conclusions</h3> This recent audit shows the effectiveness of an intensive physiotherapy-led in-patient rehabilitation programme for Ankylosing Spondylitis improving BASMI scores in the short-term and increasing physical activity behaviour over the long-term. Future work will aim to compare demographics and medical treatment differences between improvers and non-improvers. <h3>Disclosure of Interest</h3> None declared