tbuckley/cabot-search huggingface dataset:
ARTERIOSCLEROTIC MUSCULAR RIGIDITY WITH SPECIAL REFERENCE TO GAIT DISTURBANCES
Authors: WALTER L. BRUETSCH, CLIFFORD L. WILLIAMS
Journal: American Journal of Psychiatry (1954)

The syndrome of arteriosclerotic muscular rigidity results from a partial involvement of various systems (fronto-ponto-cerebellar tract, pyramidal and extrapyramidal system), rather than from an affection of 1 or 2 special cerebral centers.
P1013 MEASUREMENT OF LIVER AND SPLEEN STIFFNESS BY ARFI ELASTOGRAPHY: INTRA- AND INTER-OBSERVER VARIABILITY AND PREDICTORS OF VARIABILITY
Authors: M. Balakrishnan, F. Souza, C. Munoz, S. Augustin, N. Loo, Y. Deng, M. Ciarleglio, G. Garcia-Tsao
Journal: Journal of Hepatology (2014)
Fluorescence in situ hybridization analysis of chromosome 1 abnormalities in hematopoietic disorders: rearrangements of DNA satellite II and new recurrent translocations
Authors: M Busson-Le Coniat, F Salomon-Nguyen, N Dastugue, O Maarek, M Lafage-Pochitaloff, M-J Mozziconacci, L Baranger, F Brizard, I Radford, M Jeanpierre, OA Bernard, R Berger
Journal: Leukemia (1999)
Is vascular endothelial growth factor receptor 2 (VEGFR2) involved in systemic lupus erythematosus (SLE)? A combined structural biological and genetic approach
Authors: V Vazgiourakis, M I Zervou, E Eliopoulos, S Sharma, P Sidiropoulos, T Niewold, D T Boumpas, G N Goulielmos
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> The VEGFR2 directly regulates the formation of blood vessels, a process dependent upon the function of specialised cell-types including vascular endothelial cells. <i>VEGFR2</i> gene polymorphisms have been correlated with vascular diseases such as Coronary Heart Disease (CHD). <h3>Aim</h3> In view of the premature atherosclerosis observed in SLE, the authors sought to clarify the structural/functional consequences of two common polymorphisms in <i>VEGFR2</i> in SLE and determine whether these polymorphisms are associated with risk of SLE by influencing endothelial cells. <h3>Materials and methods</h3> Three-dimensional (3D) homology modeling of the mutation V297I was based on the 3D structure of domains D2 and D3 of VEGFR2 in complex with VEGF-C, while mutation Q472H was investigated by homology modeling on the KIT ectodomain structure. The V297I (rs2305948) and Q472H (rs1870377) single nucleotide polymorphisms (SNPs) in <i>VEGFR2</i> were genotyped with Taqman technology in 250 SLE patients and 241 healthy controls from a Greek population (Cretan). The replication sample set for the rs1870377 SNP consisted of 253, 184 and 77 patients with SLE of African-, European- and Hispanic-American origin, respectively, as well as geographically/ethnically-matched controls. <h3>Results</h3> Modeling revealed that amino acid position #297 is located on the D3 Ig-like domain of the extracellular region of VEGFR2 on a surface loop and polymorphism V297I affects the efficiency of trans-autophosphorylation and cell signaling. On the other hand, position #472 is located on the surface of the D5 domain and mutation Q472H affects homotypic contacts of membrane proximal Ig-like domains. This finding prompted us to examine whether these polymorphisms contribute to SLE risk or vascular damage. No significant difference was observed in the frequency of the minor allele <b>A</b> of rs1870377 when SLE patients were compared with controls either in the Greek population or in the 3 replication groups analysed. No association was detected between rs2305948 SNP and SLE when tested in the Greek population. <h3>Conclusions</h3> Although structural data suggest that both VEGFR2 SNPs may contribute to SLE pathogenesis by impairing cell signaling, none of the SNPs analysed was associated with increased susceptibility to SLE. Experiments in progress address the role of these polymorphisms on the number of circulating endothelial cells and their possible influence to vascular injury observed in the disease.
ADMISSION HYPERGLYCEMIA IS AN INDEPENDENT PREDICTOR OF ACUTE KIDNEY INJURY IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Authors: Noriaki Moriyama, Masaharu Ishihara, Teruo Noguchi, Hiroki Sakamoto, Michio Nakanishi, Jun-Ichi Kotani, Tetsuo Arakawa, Yasuhide Asaumi, Leon Kumasaka, Taichi Adachi, Takafumi Yamane, Tadayoshi Miyagi, Toshiyuki Nagai, Masashi Fujino, Manabu Matsumoto, Satoshi Honda, Takeshi Yagyu, Reiko Fujiwara, Akiko Fujino, Toshihisa Anzai, Wataru Shimizu, Satoshi Yasuda, Hisao Ogawa
Journal: Journal of the American College of Cardiology (2013)
FRI0009 Adamts5, Which Has Negative Correlation with IL-6, is A Biomarker for the Efficacy Prediction of TOCILIZUMAB in Rheumatoid Arthritis
Authors: K. Tsuzaka, S. Nogawa, J. Nishida
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) has been reported to play a key role in aggrecan degradation in cartilage. On the other hand, IL-6 has been shown to inhibit ADAMTS5 expression while TNFα could not suppress ADAMTS5. We have previously reported that the efficacy of biologics, infliximab and adalimumab can be predictable using baseline blood ADAMTS5 mRNA level (Ref.1,2). <h3>Objectives</h3> In this study presented here, we investigated whether the efficacy of tocilizumab (TCZ) for the treatment of rheumatoid arthritis (RA) can be predicted by the baseline blood ADAMTS5 mRNA level because of the recent reported negative correlation between IL-6 and ADAMTS5 expression. <h3>Methods</h3> Fifty-four randomly selected active RA patients were treated with TCZ. Peripheral blood samples were collected at baseline and ADAMTS5 mRNA was quantified using real-time PCR (BiologicMate®). Baseline IL-6 mRNA was also estimated using real-time PCR. <h3>Results</h3> Baseline ADAMTS5 mRNA levels (x10<sup>–4</sup>) in the responder (2.85±2.37 Index) was significantly (p=0.049) higher than that in the non-responder (1.56±0.80 Index) at 12 wks9 treatment with TCZ. Area under curve (AUC) of the ROC curve for predicting the clinical remission (DAS28&lt;2.6) using the baseline ADAMTS5 mRNA at 12 wks was 0.75, and the cut-off value of ADAMTS5 mRNA was calculated as 1.60 Index. There observed no difference in the general patient backgrounds (average age, disease duration, dose of MTX, dose of steroid, baseline DAS28, etc) between the High-ADAMTS5 (&gt;1.60 Index) group and the Low-ADAMTS5 group. However, DAS28 at 12 wks after treatment was significantly (p=0.0254) lower in the High-ADAMTS5 group (3.09±1.29) than in the Low-ADAMTS5 group (3.88±1.08) (Fig.1). The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the baseline High-ADAMTS5 (&gt;1.60 Index) for predicting the clinical remission at 12 wks with TCZ was 75.0%, 94.1%, 48.7%, 45.7%, and 94.7%, respectively. Interestingly, we observed negative correlation between baseline IL-6 and ADAMTS5 mRNA expression. <h3>Conclusions</h3> The baseline ADAMTS5 mRNA level, which might be related to baseline IL-6, is a candidate biomarker for prediction of the response to TCZ in RA patients. <h3>References</h3> Tsuzaka K, et al. ADAMTS5 is a biomarker for prediction of the response to Infliximab in patients with rheumatoid arthritis. J Rheumatol 37: 1454-1460, 2010 Tsuzaka K, et al. Expression of ADAMTS4 or ADAMTS5 could sort the prediction of response to infliximab or adalimumab in patients with rheumatoid arthritis. The EULAR annual congress of rheumatology, Rome, Italy, June, 2010 <h3>Disclosure of Interest</h3> K. Tsuzaka Shareholder of: Kaytee Bio, Co.&amp;Ltd., S. Nogawa: None declared, J. Nishida: None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2811
672 TUMOR GROWTH AND LYMPH NODE METASTASIS OF INTRAHEPATIC CHOLANGIOCARCINOMA ARE ASSOCIATED WITH hsa-miR-126 AND hsa-miR-128 EXPRESSION
Authors: M. Schmelzle, A. Thelen, G. Atanasov, L. Feldbrügge, G. Wiltberger, C. Benckert, I. Kämmerer, S. Kuhn, K. Splith, S. Jonas
Journal: Journal of Hepatology (2013)
PWE-186 Effective, Safe Management of Starved Patients with Anorexia Nervosa through a Combined Medical &amp; Psychiatric Approach-Meeting the Marsipan Challenges
Authors: R Perowne, C Wells, M Temple, D Kannan
Journal: Gut (2013)

<h3>Introduction</h3> Anorexia Nervosa (AN) has the highest mortality rate of any psychiatric condition. These patients are a challenge to manage because of severe physical and psychiatric morbidity. MARSIPAN reported that some patients with severe AN admitted to medical wards were deteriorating &amp; occasionally dying because of delays in treating their medical conditions due to obstructive behaviours relating to their psychiatric morbidity<sup>1</sup>. It recognised a need for specialist teams including a psychiatrist and physician with an interest in eating disorders. There is a medical team providing in-patient medical management at University Hospital North Tees (UHNT) with support from the community eating disorders (ED) team. <h3>Methods</h3> A retrospective audit of management of AN admissions due to starvation (BMI 13 or less) to UHNT June 2010-June 2012. Data collected from medical notes-audited against MARSIPAN standards. <h3>Results</h3> 10 patients identified, all female. Age 18–43 (median 24.5). 9 known to ED service. Median admission BMI 12.8 (9.7–13). <b>Assessment:</b> All had recommended blood tests. 8 had an ECG; 2 abnormal (long QTc, heart block). <b>Monitoring:</b> 9 had appropriate electrolyte monitoring. All weighed twice weekly &amp; had complete fluid balance charts. <b>Management:</b> 8 seen by ED physician within 48 hours (5 within 24 hrs), 6 seen by dietitian by 48 hours. All received pabrinex, 9 vitamin B &amp; multivitamins. 4 did not receive DVT prophylaxis. All reviewed at least weekly by psychiatric ED team. 7 NG fed, 4 began NG feed within 24 hours, all established by 48 hours. 7 required electrolyte replacement. <b>Complications:</b> Re-feeding syndrome (7), pneumonia (2), ITU admissions (2; pneumonia, abnormal electrolytes). 3 exhibited problematic behaviour; 2 required 1 to 1 nursing. All complications recognised early. <b>Discharge:</b> All had discharge plans agreed by the ED team, 5 discharged to the ED unit. <h3>Conclusion</h3> The ED team at UHNT provides a successful specialist service for the medical care of patients with severe AN. A median admission BMI of 12.8 indicated early identification &amp; intervention of at risk community patients through this integrated approach. Patients are appropriately assessed &amp; monitored &amp; NG feeding is quickly established. Management of these patients by the multidisciplinary team enables the medical and behavioural challenges to be dealt with effectively and ensures timely discharge once medically stable. Through the development of trust guidelines we hope to further improve care of this vulnerable group. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> MARSIPAN: Management of Really Sick Patients with Anorexia Nervosa, College Report 162, Royal College of Psychiatrists and Royal College of Physicians London, October 2010
THU0153 Improvements in disease activity score by baseline status: Pooled analysis of five phase 3 studies with tofacitinib (CP-690,550) in patients with active rheumatoid arthritis:
Authors: R.M. Fleischmann, S. Krishnaswami, D. Gruben, S.H. Zwillich, C. Mebus, J.D. Bradley
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tofacitinib (CP-690,550) is a novel, oral Janus kinase inhibitor being investigated as a targeted immunomodulator in rheumatoid arthritis. <h3>Objectives</h3> To assess efficacy of tofacitinib 5 and 10 mg twice-daily (BID) using disease activity scores (DAS) across a wide range of baseline (BL) values. <h3>Methods</h3> Demographic and BL disease characteristics of patients (pts) in five Phase 3 studies (monotherapy: NCT00814307; background DMARD: NCT00960440, NCT00847613, NCT00856544, NCT00853385) were similar. Data were pooled, and BL DAS values based on 28-joint counts using C-reactive protein (DAS28-3(CRP)) were divided into four groups (≤25th, &gt;25th-50th, &gt;50th-75th, &gt;75th percentiles); for each, mean change from BL, proportion of pts improving by ≥1.2 from BL, and proportions of pts with values ≤3.2 and &lt;2.6 at Month 3 were computed for placebo (PBO), 5 mg BID and 10 mg BID. Observed data (no imputations) were analysed. <h3>Results</h3> 3072 pts (PBO, 673; 5 mg, 1200; 10 mg, 1199) were divided into groups using BL DAS28-3(CRP) quartiles: ≤4.71 (Q1); &gt;4.71-5.34 (Q2); &gt;5.34-6.01 (Q3); &gt;6.01 (Q4). In each group, both tofacitinib doses demonstrated clinically significant improvements in DAS28-3(CRP)-based analyses compared with PBO. Pts with higher BL values had greater mean reductions in DAS, with correspondingly larger differences from PBO. All BL groups showed numerical benefit of 10 mg BID over 5 mg BID across all DAS28-3(CRP)-based analyses and the proportions of pts achieving various DAS thresholds were 2-13 percentage points greater with 10 mg BID vs 5 mg BID. Data for Q1 and Q4 are shown in Table 1. <h3>Conclusions</h3> Across a range of BL disease activities, tofacitinib was consistently efficacious at both doses in reducing DAS28-3 (CRP) vs PBO. All groups showed numerical benefit in efficacy of 10 mg BID over 5 mg BID across all measures of DAS28-3 (CRP); the magnitude of benefit of 10 mg BID over 5 mg BID appeared to be independent of BL status. As expected, pts in the lowest quartile were more likely to achieve DAS28-3(CRP) ≤3.2 and &lt;2.6 than pts in the highest quartile. Even though pts with higher BL disease activity reached the target to a lesser extent, it remains achievable in this population. Similar analyses of other composite disease activity indices are required to confirm these results. <h3>Disclosure of Interest</h3> R. Fleischmann Grant/Research support from: Pfizer Inc, Consultant for: Pfizer Inc, S. Krishnaswami Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Gruben Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Zwillich Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Mebus Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Bradley Shareholder of: Pfizer Inc, Employee of: Pfizer Inc
Identification of key regulators of pancreatic cancer progression through multidimensional systems-level analysis
Authors: Deepa Rajamani, Manoj K. Bhasin
Journal: Genome Medicine (2016)

Pancreatic cancer is an aggressive cancer with dismal prognosis, urgently necessitating better biomarkers to improve therapeutic options and early diagnosis. Traditional approaches of biomarker detection that consider only one aspect of the biological continuum like gene expression alone are limited in their scope and lack robustness in identifying the key regulators of the disease. We have adopted a multidimensional approach involving the cross-talk between the omics spaces to identify key regulators of disease progression.Multidimensional domain-specific disease signatures were obtained using rank-based meta-analysis of individual omics profiles (mRNA, miRNA, DNA methylation) related to pancreatic ductal adenocarcinoma (PDAC). These domain-specific PDAC signatures were integrated to identify genes that were affected across multiple dimensions of omics space in PDAC (genes under multiple regulatory controls, GMCs). To further pin down the regulators of PDAC pathophysiology, a systems-level network was generated from knowledge-based interaction information applied to the above identified GMCs. Key regulators were identified from the GMC network based on network statistics and their functional importance was validated using gene set enrichment analysis and survival analysis.Rank-based meta-analysis identified 5391 genes, 109 miRNAs and 2081 methylation-sites significantly differentially expressed in PDAC (false discovery rate ≤ 0.05). Bimodal integration of meta-analysis signatures revealed 1150 and 715 genes regulated by miRNAs and methylation, respectively. Further analysis identified 189 altered genes that are commonly regulated by miRNA and methylation, hence considered GMCs. Systems-level analysis of the scale-free GMCs network identified eight potential key regulator hubs, namely E2F3, HMGA2, RASA1, IRS1, NUAK1, ACTN1, SKI and DLL1, associated with important pathways driving cancer progression. Survival analysis on individual key regulators revealed that higher expression of IRS1 and DLL1 and lower expression of HMGA2, ACTN1 and SKI were associated with better survival probabilities.It is evident from the results that our hierarchical systems-level multidimensional analysis approach has been successful in isolating the converging regulatory modules and associated key regulatory molecules that are potential biomarkers for pancreatic cancer progression.
SYNTAX SCORE AND ITS IMPACT ON LONG TERM OUTCOMES OF CORONARY REVASCULARIZATION: A META-ANALYSIS AND META-REGRESSION
Authors: Alok Saurav, Vimal Kandasamy, Ajay Kumar Kaja, Arun Kanmanthareddy, Saurabh Aggarwal, Aiman Smer, Manu Kaushik, Venkata Alla, Aryan Mooss
Journal: Journal of the American College of Cardiology (2016)
RESULTADOS DEL PROGRAMA DE CRIBADO DE CCR DE LA COMUNIDAD VALENCIANA. COMPARATIVA TSOH BIOQUÍMICO FRENTE A TSOH INMULÓGICO
Authors: M Ponce Romero, C Gisbert, JR Moles Marco, J Hinojosa Del Val, A Peris Trias, MS Siles Moreno, F De Vera, MN Braithwaite Flores Ana, V Pons Beltran
Journal: Endoscopy (2013)

Introducción: El cáncer colorrectal (CCR) es un problema de Salud Publica dada su incidencia y mortalidad. Es susceptible de prevención por lo que la implantación de programas de cribado de CCR (PPCCR) es una realidad en muchas regiones de nuestro país. En la Comunidad Valenciana (CV) se instauró en 2006 y va dirigido a sujetos de 50 – 69 años. Utiliza como prueba de cribado el test de sangre oculta en heces (TSOH), indicándose la colonoscopia en los positivos. Objetivo: Describir los resultados del PPCCR de la CV considerando 2 periodos de tiempo (2005 – 2009 y 2009 – 2011) que difieren en el TSOH utilizado; bioquímico (TSOHg) e inmunológico (TSOHi). Material y Método: Análisis retrospectivo de indicadores básicos del PPCCR de la CV entre 2006 – 2011. Resultados: Entre 2006 – 2011 se incluyeron en el PPCCR a 448.473 sujetos de 50 – 69 años del total de la población diana de la CV (1.097.536 sujetos), lo que supone un 40.86% cobertura. Aceptaron la realización del TSOH 178.596 sujetos (tasa de participación global 39.82%, superior con TSOHg que con TSOHi, 41.59% vs. 37.51%). La tasa de positividad fue mayor con el TSOHi (6.29% frente 1.15%). Se realizaron un total de 3758 colonoscopias, con una tasa de aceptación a la exploración del 87.5%, similar en ambos periodos. La colonoscopia fue completa en el 92.3%. Se detectaron lesiones significativas (adenoma alto riesgo (AAR) y/o CCR invasivo) en casi la mitad de los pacientes (48.05%), algo mayor con TSOHi y significativamente superior en hombres. La tasa de detección de AAR y CCR para TSOHi y TSOHg fue de 13.28‰ vs. 3.49‰ y 3.08‰ vs. 1.16‰, respectivamente. Conclusiones: El PPCCR de la CV ha mostrado una alta participación y aceptación de la colonoscopia así como una alta tasa de detección de lesiones avanzadas que es mayor en los hombres y con la utilización del TSOHi.
Abstract P2-13-04: Superior efficacy of anastrozole to tamoxifen as adjuvant therapy for postmenopausal patients with hormone-responsive breast cancer. Efficacy results of long-term follow-up data from N-SAS BC 03 trial
Authors: S Imoto, S Osumi, K Aogi, Y Hozumi, H Mukai, H Iwata, I Yokota, T Yamaguchi, Y Ohashi, T Watanabe, Y Takatsuka, T Aihara
Journal: Cancer Research (2012)

Abstract Background: Aromatase inhibitors have been shown to be superior to tamoxifen as adjuvant therapy in postmenopausal patients with hormone-responsive breast cancer. Here we report the efficacy results of long-term follow-up data from N-SAS BC 03 trial (UMIN CTRID: C000000056), in which anastrozole was compared to tamoxifen in hormone-responsive postmenopausal early breast cancer patients who had taken tamoxifen for 1—4 years out of a total of 5 years of treatment as adjuvant therapy. Patients and methods: Out of a total of 706 recruited patients, 696 patients (tamoxifen group, n=345; anastrozole group, n=351) were used as the full analysis set for the present study. The log-rank test was used to compare the two groups in terms of disease-free survival (DFS) and relapse-free survival (RFS), Kaplan-Meier estimates were calculated. The treatment effects were estimated by Cox's proportional hazard model and were expressed as hazard ratios, with associated 95% confidence intervals (CIs). Results: After a median follow-up of 76.1 months, (range: 1.3–110 months), the unadjusted hazard ratio was 0.87 (95%Cl 0.60–1.26; log-rank p = 0.457) for DFS and 0.77 (95%Cl 0.49–1.22; log-rank p = 0.266) for RFS, both in favor of anastrozole. The estimated hazard ratio (95%CIs) for DFS and for RFS until each time point (right censored data) was as follows: until 30 months: 0.54 (0.30–0.98) and 0.48 (0.23–0.98), until 42 months; 0.65 (0.40–1.06) and 0.53 (0.29–0.97), until 54 months: 0.77 (0.50–1.19) and 0.63 (0.37–1.06), until 66 months: 0.82 (0.55–1.24) and 0.72 (0.44–1.17), until 78 months: 0.83 (0.57–1.23) and 0.73 (0.46–1.17), respectively. The hazard ratios (95%CIs) for DFS and for RFS until 36 months were 0.72 (95%Cl 0.43–1.22) and 0.58 (95%Cl 0.30–1.12), and those after 36 months were 1.06 (95%Cl 0.62–1.81) and 0.98 (95%Cl 0.51–1.88), respectively. Conclusion: Superior efficacy of anastrozole to tamoxifen in the Japanese population was suggested over a long-term follow-up period. It was the greatest early after switching from tamoxifen and then decreased thereafter. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-13-04.