tbuckley/cabot-search huggingface dataset:
Abstract 5070: Paired-end RNA-sequencing reveals novel fusion genes and SNVs in osteosarcoma
Authors: So Young Moon, Sven Bilke, Sean Davis, Robert L. Walker, Marbin Pineda, Yuelin Jack Zhu, Ogan Abaan, Paul S. Meltzer
Journal: Cancer Research (2012)

Abstract Osteosarcoma is an aggressive cancer of bone, which typically occurs during adolescence. The genetic hallmark of osteosarcoma is the presence of extensive and complex genomic rearrangements. However, few consistent aberrations have been identified, hampering the development of targeted therapy for osteosarcoma. Next generation RNA-sequencing (RNA-seq) is a powerful tool for comprehensive characterization of whole transcriptome, with the unique ability of identifying novel fusion genes. We applied paired-end RNA-seq to explore the transcriptome of 16 human OS cell lines and primary osteoblasts from two healthy individuals. On average, about 21.6 million sequencing reads and 10.6 million aligned reads were obtained for each sample. Several thousand SNVs (single nucleotide variants) that have not been reported in the dbSNP database were identified. Bioinformatic analysis identified several fusion genes (e.g. PAFAH1B2-FOXR1and FAM119B-TSFM), which involved both known cancer related genes as well as genes previously unrelated to cancer. Fusion transcripts were validated using RT-PCR, Western blot and capillary sequencing. These rearrangements tended to occur at copy number transitions on the partner chromosome regions. Our findings have the potential to provide important insights into osteosarcoma biology, and potential translational applications for diagnostic and therapeutic development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5070. doi:1538-7445.AM2012-5070
PTH-093 Efficacy of Methotrexate in Ulcerative Colitis: A District General Hospital Experience
Authors: R Basuroy, H E Johnson, T Hollingworth, S A Weaver, S D McLaughlin
Journal: Gut (2013)

<h3>Introduction</h3> Uncontrolled studies have reported methotrexate (MTX) to be efficacious in patients with Ulcerative Colitis (UC). British Society of Gastroenterology guidelines recommend MTX in patients who are unresponsive or intolerant of thiopurines. Biologics are not available for UC because of local funding restrictions. Our practise is to only consider MTX in UC patients who have failed thiopurine therapy despite dose optimisation, including allopurinol co-therapy, to achieve therapeutic 6-thioguanine (TGN) and normal methylmercaptopurine nucleotide (MMPN) levels. To the best of our knowledge this is the first study to assess the clinical outcome of UC patients treated with MTX following thiopurine dose optimisation. <h3>Methods</h3> Patients with UC treated with MTX were identified from a prospective IBD database. Outcomes following treatment with thiopurines were identified. All patients received MTX with folic acid supplementation. Patients were loaded with intramuscular 25mg MTX for 16 weeks followed by weekly maintenance MTX of 15mg. Clinical response at 16 weeks and 12 months was used to assess the efficacy of MTX. <h3>Results</h3> 9 patients (male = 8) with UC treated with MTX were identified. Median age was 47.3 years (range; 24.8–77.8). Median time since diagnosis was 4.5 years (range; 1–25.5). Disease extent was extensive (n = 5), left sided (n = 1) and rectosigmoiditis (n = 3). Thiopurines had previously been discontinued in 9 patients because they were intolerant (n = 5) or unresponsive (n = 4) despite therapeutic TGN and normal MMPN levels. 2 patients (22%) entered a steroid-free clinical remission with MTX at 16 weeks, which was sustained at 12 months. Both were intolerant of thiopurines because of severe nausea and dyspepsia. 7 patients (78%) discontinued MTX at 16 weeks because of a lack of response (n = 6) or side effects (n = 1, pneumonitis). Clinical outcomes at 12 months for patients who failed MXT were colectomy (n = 4), arsenic suppositories (n = 2), and diagnostic reclassification (n = 1) to Crohn’s disease with CMV colitis treated with ganciclovir and infliximab. <h3>Conclusion</h3> The efficacy of MTX in UC patients in this study was poor with a low clinical response rate (22%) and high colectomy rate (44%). Previous retrospective studies have reported MTX to be efficacious in patients failing thiopurines without reporting on the use of thiopurine optimisation. This study suggests that MTX has limited use in UC patients who are unresponsive to thiopurines despite dose optimisation. <h3>Disclosure of Interest</h3> R. Basuroy: None Declared, H. Johnson Conflict with: Sponsorship from Falk, Abbott &amp; Warner Chilcott to attend meetings, T. Hollingworth: None Declared, S. Weaver Consultant for: MSD advisory board, Conflict with: Sponsorship from Falk, Abbott, MSD &amp; Ferring to attend meetings, S. McLaughlin Conflict with: Sponsorship from Falk to attend meetings
THU0496 [18F] Fdg Uptake in Proximal Muscles Assessed by Pet/Ct Reflects Both Global and Local Muscular Inflammation and Provides Useful Information in the Management of Patients with Polymyositis/Dermatomyositis
Authors: S. Tanaka, K. Ikeda, K. Uchiyama, T. Iwamoto, Y. Sanayama, A. Okubo, D. Nakagomi, K. Takahashi, M. Yokota, A. Suto, K. Suzuki, H. Nakajima
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Although the utility of [<sup>18</sup>F] fluoro-deoxy-glucose-positron emission tomography/computed tomography ([<sup>18</sup>F] FDG-PET/CT) in the management of rheumatic or inflammatory diseases has been increasingly reported, its applications and benefits in the management of polymyositis (PM)/dermatomyositis (DM) are still controversial [1,2]. <h3>Objectives</h3> This study aimed to determine whether [<sup>18</sup>F] FDG-PET/CT discriminates PM/DM from non-muscular diseases and also whether the FDG uptake in proximal muscles reflects the activity and severity of muscular inflammation in PM/DM. <h3>Methods</h3> Twenty treatment-naïve PM/DM patients who underwent [<sup>18</sup>F] FDG-PET/CT were retrospectively identified by reviewing medical records. The same number of age- and sex-matched control patients with non-muscular diseases were also identified. Standardized uptake value (SUV) was calculated for each of the seven proximal muscles. For patient-based assessment, mean proximal muscle SUV was calculated by averaging the SUVs for these proximal muscles bilaterally. <h3>Results</h3> Mean proximal muscle SUVs were significantly greater in PM/DM patients than those in control patients (median 1.05 vs. 0.69, <i>P</i> &lt; 0.001). Mean proximal muscle SUVs significantly correlated with mean proximal manual muscle test scores (rho = -0.48, <i>P</i> = 0.028) and serum levels of creatine kinase (rho = 0.54, <i>P</i> = 0.015) and aldolase (rho = 0.64, <i>P</i> = 0.002). Furthermore, SUVs in proximal muscles from which biopsy specimens were obtained significantly correlated with the histological grades for inflammatory cell infiltration (rho = 0.66, <i>P</i> = 0.002). <h3>Conclusions</h3> Our results suggest that [<sup>18</sup>F] FDG-PET/CT is useful in the diagnosis of PM/DM when inflammation in proximal muscles is globally assessed with quantitative measures. Our results also indicate that the local FDG uptake in a proximal muscle reflects the activity of inflammation in the same muscle and provides useful information in determining the region for muscle biopsy. <h3>References</h3> Pipitone N, Versari A, Zuccoli G, et al. 18F-Fluorodeoxyglucose positron emission tomography for the assessment of myositis: a case series. Clin Exp Rheumatol 2012;30:570-3. Owada T, Maezawa R, Kurasawa K, Okada H, Arai S, Fukuda T. Detection of inflammatory lesions by f-18 fluorodeoxyglucose positron emission tomography in patients with polymyositis and dermatomyositis. J Rheumatol 2012;39:1659-65. <h3>Disclosure of Interest</h3> None Declared
COMPARISON OF GATED SPECT EJECTION FRACTION (EF) POST EXERCISE AND ADENOSINE STRESS TO RESTING EJECTION FRACTION AMONG PATIENTS WITH AND WITHOUT CORONARY ARTERY DISEASE (CAD).
Authors: Haresh Majmundar, Renee Fabrizi-Bames, Calvin Hou, Nancy Prill, Sue Clemente, Daniel Kulick, Jennifer Thomas, Gregory Thomas
Journal: Clinical Nuclear Medicine (1998)

s Presented At The 22Nd Annual Western Regional Meeting Of The Society Of Nuclear Medicine October 1997
AB0089 Prevalence of metabolic syndrome in the moroccan population with rheumatoid arthritis: results from the quest-ra study.
Authors: L. Bouazzaoui, S. Rostom, L. Benbrahim, B. Benchekroun, S. Ahid, R. Bahiri, N. Hajjaj-hassouni
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To evaluatethe prevalence of metabolic syndrome in patients with rheumatoid arthritis and analyze the factors that are associated with its presence. <h3>Methods</h3> QUEST-RA Moroccan inspired by Finland QUEST-RA (Quantitative monitoring of standard patients with rheumatoid arthritis) is a multinational cross-sectional study, including patients with rheumatoid arthritis, according the criteria for diagnosis of ACR 1987, and collected in several Moroccan centers combining the public and private sector over a period of two years (from January 2008 to December 2010). A questionnaire containing sociodemographic, clinical and paraclinical parameters was completed by all patients. The definition of theWorld Health Organization (WHO 1998) was used to identify the metabolic syndrome. Metabolic syndrome is defined as the presence of at least two of the four following factors (obesity (BMI&gt; 30 kg/m2), diabetes, hypertension, dyslipidemia). <h3>Results</h3> 1129exploitable files were analyzed. The mean age of patients was 48.8 ± 12.7 years with female predominance 87.3%. The median disease duration was 6 years (3, 12), the mean DAS28 was 4.94 ± 1.68, with a median HAQ of1 (0.37, 1.62). The prevalence of hypertension, diabetes, hyperlipidemia, and obesity was respectively 13.7%, 8.3%, 4.4%, 17.6%. The prevalence of metabolic syndrome according to the WHO definition was 8.1%. In univariate analysis, the presence of metabolic syndrome was associated with a higher age of patients (p &lt;0.0001) and a longer disease duration (p = 0.04) compared to the group without metabolic syndrome. In addition, there was no association between the presence of metabolic syndrome and DAS 28, ESR, CRP, The consumption of alcohol and tobacco, taking the dose of corticosteroids, the presence of bone erosions, anti-CCP and rheumatoid factor. <h3>Conclusions</h3> This study suggeststhat there is no increased frequency of metabolic syndrome in rheumatoid arthritis in Morocco compared to literature data. The presence of metabolic syndrome was associated with age and disease duration of the disease unrelated to the activity or severity of the disease. Comparison with a control group and larger multiethnic studies are necessary. <h3>Disclosure of Interest</h3> None Declared
The Prognosis for Seizure Control in Newly Diagnosed Epilepsy
Authors: Robert D. C. Elwes, Anthony L. Johnson, Simon D. Shorvon, Edward H. Reynolds
Journal: New England Journal of Medicine (1984)

We assessed the prognosis for seizure control in 106 patients who were referred to an adult neurology clinic with previously untreated tonic-clonic, partial, or mixed seizures and were followed prospectively for a median of 66 months (range, 6 to 96). Twenty-six patients remained completely free of seizures for as long as they were followed. Actuarial analysis showed that 35 per cent of patients could be expected to enter a seizure-free period of at least two years at the start of treatment, 73 per cent would have had a two-year seizure-free period at the end of four years, and 82 per cent would have had a two-year seizure-free period at the end of eight years. Of 79 patients whose seizures were completely controlled for at least two years, 51 subsequently remained seizure-free. If seizures continued for up to two years after the start of treatment, the probability of subsequent seizure control fell by half. The presence of partial seizures; a high frequency of tonic-clonic seizures before treatment; a neurologic, social, or psychiatric handicap; and a family history of epilepsy each indicated a worse prognosis. We conclude that the long-term pattern of seizure control is largely established during the first two years of treatment.
Evaluation of response to neoadjuvant chemotherapy in primary breast cancer using PET.
Authors: J Choi, K Kim, W Kim, S Lee, H Lim, E Cho, B Han, Y Kim, J Ahn, Y Im, J Lee, S Nam, J Yang
Journal: Cancer Research (2009)

Abstract Abstract #4019 Purpose&amp;#x2028; To estimate the usefulness of PET scan to assess the response of neoadjuvant chemotherapy, PET scan results were compared with conventional imaging modalities(US and MRI).&amp;#x2028; Patients and Methods&amp;#x2028; Fourty-one patients undergoing neoadjuvant chemotherapy between December 2004 and March 2008 were included. PET scan was performed before and after chemotherapy. Pathologic results were classified into two groups; pathological complete response(pCR) and non-pCR. Clinical responses were assessed with the results of imaging modalities such as post-chemotherapy size or pSUV(postTx), size difference between treatment(delta) and reduction rate(RR) of size or pSUV, and they are compared with postoperative pathologic results.&amp;#x2028; Results&amp;#x2028; 7 out of 41 patients (17.1%) had pCR. The results of US shows that postTx size (1.7±1.5cm) of pCR was not dfferent from those of non-pCR (3.6±3.0cm), and the delta (3.1±1.9cm) and RR (67.7±29.1%) of pCR were higher than those of non-pCR (1.3±1.3cm, 31.0±25.4%), respectively. As a result of MRI, postTx size, delta, RR of pCR was differ from those of non-pCR (1.0±1.7cm vs 2.8±1.7cm p&amp;lt;0.05; 4.5±1.0cm vs 2.3±1.8cm, p&amp;lt;0.05; 88.0±20.8% vs 44.6±24.7%, p&amp;lt;0.01). In PET scan, only postTx pSUV of pCR was differ from that of non-pCR (1.4±1.3 vs 5.3±8.3cm, p&amp;lt;0.05). As a result of receiver operating characteristic curve analyses for the prediction of pathological response of breast cancer, area under curve values (95% confidence interval) of US, MRI, PET for delta were 0.83(0.69∼0.98), 0.91(0.80∼1.01), 0.62(0.38∼0.86), and those of RR were 0.80(0.60∼0.99), 0.90(0.77∼1.02), 0.72(0.47∼0.96), respectively&amp;#x2028; Conclusions&amp;#x2028; We suggest that MRI is useful method to evaluate the response of neoadjuvant chemotherapy. Although PET scan shows less effective for evaluating the response of chemotherapy than MRI, PET scan with the ability to detect the distant metastatic lesions may be helpful to decide the proper management plans for advanced breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4019.
Regional Cardiac Sympathetic Denervation and Systolic Compression of a Septal Perforator Branch in a Sudden Death Survivor with Hypertrophic Cardiomyopathy
Authors: Jimin Han, Dae Hyuk Moon, You Ho Kim
Journal: Clinical Nuclear Medicine (2002)

Hypertrophic cardiomyopathy is a heterogeneous primary cardiac disease with a broad clinical spectrum, including a high risk for sudden death in a certain subgroup of patients. However, the precise criteria for identifying the subgroup at high risk have not been established. The authors describe a 41-year-old man with hypertrophic cardiomyopathy who was examined after an episode of aborted sudden death. Extensive invasive and noninvasive investigations did not reveal a cardiac abnormality other than severe sympathetic denervation in the midbasal septal wall on iodine-123 MIBG SPECT imaging and concentric left ventricular hypertrophy on echocardiography. A retrospective review of the cardiac catheterization findings, however, revealed systolic compression of a septal perforator artery. The aborted sudden death of the patient was most likely associated with systolic compression of a septal branch or sympathetic denervation, which may have precipitated a ventricular arrhythmia in this patient.
Abstract 4845: Tumor cell line profiling of eighteen cancer therapeutics to evaluate relationships between tumor genotypes and cancer cell sensitivities
Authors: Yulia Y. Ovechkina, Christine O'Day, Karen Marcoe, Robert Keyser, Karen Bernards, Jessica Chesnut-Speelman, Phuong Nguyen, Janine Mulligan, Teddy Lin, Rodney Shively, Jim Hnilo, Brian Nelson
Journal: Cancer Research (2011)

Abstract In vitro cellular response profiling of tumor human cell lines has become a widely used approach for the targeted cancer therapeutics development. Correlation of the drug sensitivity and resistance cellular response with genomic data offers a robust and sensitive system for predicting clinical efficacy and identifying more efficacious patient populations. We have developed a high throughput cellular approach to evaluate the relationship between tumor genotypes and drug sensitivity over 240 human tumor cell lines. A panel of the cancer therapeutic agents was tested for proliferative, apoptotic and cell cycle arrest responses using multiplexed high content screening with automated fluorescence microscopy and image analysis based technology. Growth index was measured using nuclear dye. Activated caspase 3 antibodies were used for the apoptosis induction detection. Phospho-histone H3 antibodies were used to measure the cell cycle block. The eighteen cancer therapeutics were used in this study: BMS-387032 (SNS-032), PD0325901, PD173074, API-2 (Triciribine), Lapatinib (Tykerb), BMS-536924, Geldanamycin, Sorafenib, Dasatinib, Erlotinib, VX-680, Sunitinib, Everolimus, Tandutinib, Cl 1040, Doxorubicin, Paclitaxel and Staurosporine. We generated cell line profiles to reveal drug sensitivity and resistance patterns and identified markers associated with a specific response. It was found that Raf/Ras mutations confer sensitivity to MEK inhibitors, PD0325901 and Cl 1040, while PIK3CA and RB mutations were associated with resistance. Resistance to IGF-1R, FGFR, and EGFR inhibitors correlated with PI3K/PTEN/Akt or Raf/Ras pathway activation. EGFR mRNA overexpression was associated with resistance to FGFR and IGF-1R inhibitors. Resistance to AKT inhibitor, API-2 (Triciribine) was associated with PTEN mutations and amplification of AKT. APC mutations were associated with resistance to Aurora kinase inhibitor, VX-680, while mutations in the beta-catenin gene were linked with a sensitive phenotype. This approach could provide insight into the mechanisms of enhanced susceptibility or resistance which in turn could be used for the optimization of the targeted cancer therapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4845. doi:10.1158/1538-7445.AM2011-4845
Suicidal Ideation and Suicide Attempts in Panic Disorder and Attacks
Authors: Myrna M. Weissman, Gerald L. Klerman, Jeffrey S. Markowitz, Robert Ouellette
Journal: New England Journal of Medicine (1989)

Panic disorder, which is found in about 1.5 percent of the population at some time in their lives, includes recurrent episodes of sudden, unpredictable, intense fear accompanied by symptoms such as palpitations, chest pain, and faintness. Panic attacks, which do not meet these diagnostic criteria fully, are two to three times more prevalent. Since panic symptoms can mimic those of other medical disorders, patients with these symptoms use medical services frequently. To determine the risk of suicidal ideation and suicide attempts in panic disorder and attacks, we studied a random sample of 18,011 adults drawn from five U.S. communities. Subjects who had panic disorder, as compared with other psychiatric disorders, had more suicidal ideation and suicide attempts, with an adjusted odds ratio for suicide attempts of 2.62 (95 percent confidence interval, 1.83 to 3.74). The odds ratio was 17.99 (95 percent confidence interval, 12.18 to 26.58) when the group with panic disorder was compared with subjects who had no psychiatric disorder. Twenty percent of the subjects with panic disorder and 12 percent of those with panic attacks had made suicide attempts. These results could not be explained by the coexistence of major depression or of alcohol or drug abuse. We conclude that panic disorder and attacks are associated with an increased risk of suicidal ideation and suicide attempts. Physicians working in general medical settings and emergency departments should be alert to this problem. (N Engl J Med 1989; 321: 1209–14.)
Neonatal Gastric Hemorrhage Showing Gallbladder Visualization with Tc-99m Red Blood Cell Scintigraphy
Authors: DOUGLAS HOWARTH, PATRICIA DAVIDSON
Journal: Clinical Nuclear Medicine (2002)

HOWARTH, DOUGLAS F.R.A.C.P.*; DAVIDSON, PATRICIA M.D., F.R.C.P., F.R.C.S., F.R.A.C.S.† Author Information
PWE-233 Single centre comparison of mortality, hospital recorded serious adverse events (SAE) and primary care recorded opportunistic infections (OI) in IBD patients treated with anti-TNF compared to thiopurines alone: Abstract PWE-233 Figure 1
Authors: O Waters, M Saunders, M Bulsara, T Ahmad
Journal: Gut (2012)

<h3>Introduction</h3> The safety profile of anti-TNF therapy in IBD has been examined in previous case series, however these have been in tertiary centres, have not included a control cohort, or review of primary care records. We aimed to review SAE including primary care recorded OI, in patients treated with anti-TNF compared to a thiopurine alone. <h3>Methods</h3> We studied two IBD cohorts: Cohort 1—All 212 anti-TNF treated patients between 1999 and 2010. Cohort 2—220 responders to an invitation sent to 365 patients treated with thiopurines only. A review of primary and secondary care records was conducted. A primary care OI was defined as any infection diagnosed or treated in primary care. Statistical analysis was performed using Stata V.12 software. Proportional hazard regression model was used to assess mortality. Other SAE and OI were studied using logistic regression, t-test, and χ<sup>2</sup> with Fishers exact. <h3>Results</h3> Cohort 1: 137 (64.5%) CD patients. 170 (80%) received Infliximab (IFX) as their only anti-TNF treatment, 34 (16%) IFX and Adalimumab (ADA) and 8 (4%) ADA only. Cohort 2: 220 patients comprising 88 (40%) CD. The mean age at drug initiation was 35.3 (SD 16.1) yrs in cohort 1, 45.7 (SD 15.9) yrs in cohort 2 (p&lt;0.0001). Median follow-up after drug initiation in cohort 1 was 2.7 years (0–11.0), total 714.9 yrs, in cohort 2 6.4 (0–30.8) yrs, total 1524 yrs. There were 8 (4%) deaths in cohort 1 (1 cardiovascular (CVS), 3 sepsis, 3 solid organ malignancies, 1 haematological malignancy) and 5 (2%) deaths in cohort 2 (2 CVS, 2 sepsis, 1 haematological malignancy). Cohort 1 patients had a higher mortality when corrected for age at diagnosis (HR 3.4 95% CI 1.1 to 10.5) Abstract PWE-233 figure 1. In cohort 1 there were two cases of demyelination (1 suspected), 1 TB reactivation, 40 in-patient treated infections, 8 malignancies, seven cases of <i>Clostridium difficile</i> and no drug induced lupus. Hospital recorded SAE did not differ between cohorts 1 and 2 and no risk factors were identified. The mean number of primary care recorded OI was 5.8 (SD 5.8) in cohort 1 and 4.5 (SD 4.2) in cohort 2. <h3>Conclusion</h3> The age at diagnosis adjusted mortality of IBD patients treat with anti-TNF is significantly greater than patients treated with thiopurines alone. Causality is unclear and may reflect underlying disease severity. Anti-TNF treated patients have similar rates of other SAE and primary care OI compared to patients treated with thiopurines alone. <h3>Competing interests</h3> None declared.