tbuckley/cabot-search huggingface dataset:
AB0780 Identification of Knee OA Phenotypes: A Replication Study Using Data from the Amsterdam Osteoarthritis Cohort
Authors: J. Knoop, M. van der Esch, L.D. Roorda, M. van der Leeden, D.L. Knol, W.F. Lems, J. Dekker
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> We previously identified 5 clinically relevant phenotypes from a heterogeneous knee OA population (Osteoarthritis Initiative [OAI] cohort), which needs to be replicated for validation. <h3>Objectives</h3> The present study aims to replicate this phenotype identification for validation in a clinical setting using data from the Amsterdam Osteoarthritis (AMS-OA) cohort. <h3>Methods</h3> K-means clustering analysis was performed in 374 knee OA patients from the AMS-OA cohort, using 4 clinically relevant and easily obtainable patient characteristics or clustering variables: radiographic severity (Kellgren/Lawrence [K/L] grade), body mass index (BMI), upper leg muscle strength, and depression (from Hospital Anxiety and Depression Scale [HADS] questionnaire). The cluster solution with the highest Pseudo F value was considered the most adequate number of clusters or phenotypes in the dataset. This solution was compared with the original study. <h3>Results</h3> The most adequate number of phenotypes was 5, similar as in the original study. Moreover, the 5 identified phenotypes represented in general similar phenotypes compared to the original study, namely a "minimal joint disease phenotype", a "strong muscle phenotype", a "non-obese weak muscle phenotype" (although obesity was more prevalent compared to the original study), an "obese weak muscle phenotype", and a "depressive phenotype" (although depression was less prevalent compared to the original study). <h3>Conclusions</h3> The identification of phenotypes from the OAI cohort could be replicated, except for two minor differences that are presumably attributable to differences in study population. The phenotype identification seems therefore a valid finding, with phenotypes possibly representing different etiological subtypes of knee OA in which phenotype-specific interventions may be needed. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3277
Phenobarbital Compared with Phenytoin for the Treatment of Neonatal Seizures
Authors: Michael J. Painter, Mark S. Scher, Aryeh D. Stein, Stacey Armatti, Zhiming Wang, Joseph C. Gardiner, Nigel Paneth, Beth Minnigh, John Alvin
Journal: New England Journal of Medicine (1999)

Seizures occur in 1 to 2 percent of neonates admitted to an intensive care unit. The treatment is usually with either phenobarbital or phenytoin, but the efficacy of the two drugs has not been compared directly.
Case 1-2003
Authors: Lynn T. Tanoue, Eugene J. Mark
Journal: New England Journal of Medicine (2003)

Presentation of CaseA 43-year-old man was admitted to the hospital because of fever, night sweats, weight loss, and headache.The patient had reportedly been well until 15 days earlier, when fever developed. A physician prescribed an unknown medication, but the fever persisted, and on the day of admission the patient's temperature was 40.1°C.The patient was a native of Morocco and had immigrated to this country in the autumn, four months before admission. An eight-year-old son was said to have “dormant tuberculosis.” The patient reported a four-month history of night sweats, a three-month history of “generalized arthralgias,” a two-week . . .
Paroxysmal Hypertension and Hypovolemia
Authors: Jay N. Cohn
Journal: New England Journal of Medicine (1966)

CATECHOLAMINE release produces a clinical picture characterized by hypertension, anxiety, sweating and tachycardia. Blood volume is often reduced in pheochromocytoma,1 and hypovolemia has been implicated as a cause of the shock that occasionally complicates the preoperative or postoperative course.2 Essential hypertension, however, is not usually associated with signs of sympathoadrenal discharge or with reduced blood volume.3 , 4 Recently 3 patients were observed who exhibited paroxysmal elevation of blood pressure with many features suggesting catecholamine release. Despite intensive investigation no evidence for pheochromocytoma could be found. The development of shock in response to minimal stresses in all 3 patients suggests that they . . .
SP0138 Rheumatoid Arthritis Flare is More than a High Joint Count: Patient Perspectives on Flare
Authors: S. Hewlett
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> In rheumatoid arthritis, even with good inflammatory control, there are often episodes of increased inflammation (flare), which may prompt change in medication. However, there is no international definition of flare from either clinician or patient perspective. Whilst little is known about how professionals judge flare, even less is known about the patient experience, yet it may be an important indicator of increasing inflammation, may prompt a request for help, and may be an important way of exploring efficacy of new medications. This lecture will present the findings of an international study to explore the patient perspective of flare. The qualitative study was conducted across 5 countries, seeking to understand the patient perspective of flare, how and at what point they make a decision to seek help, whether there is an early warning that predicts flare, and how they manage flare. We also sought to examine the terminology used and how they might prefer a patient measure to be designed to capture flare. The patient perspective on flare, which will be presented, demonstrated much wider concepts than the traditional variables of painful, swollen joints (for example "I feel like a tractor has run over me"). Capturing this perspective has informed our thinking around the measurement of flare,enabling a merger of patient expertise with professional expertise. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6207
Positron Emission Tomography in the Detection and Management of Sarcomatous Transformation in Neurofibromatosis
Authors: STEPHEN B. SOLOMON, A. SEMIH DOGAN, THERESA L. NICOL, JAMES N. CAMPBELL, MARTIN G. POMPER
Journal: Clinical Nuclear Medicine (2001)

Benign neurofibromas undergo sarcomatous transformation in approximately 5% of patients with neurofibromatosis type I. The clinical and radiologic diagnosis of sarcomatous change remains difficult. Positron emission tomography with F-18 fluorodeoxyglucose is a method to assess increased glucose metabolism in malignant tissue such as sarcomas. In this case report, positron emission tomography accurately distinguished malignant from benign neurofibromas. The technique may be useful as a noninvasive screening tool for malignant transformation of neurofibromas.
Abstract P5-14-15: Contralateral Prophylactic Mastectomy: Clinical and Pathological Features of Women Treated at the University of Louisville
Authors: RR Johnson, PN Barry, B Kruse, AE. Dragun
Journal: Cancer Research (2010)

Abstract Objective: To evaluate the clinical and pathological features of women who underwent contralateral prophylactic mastectomy (CPM) as a component of breast cancer therapy. Materials &amp; Methods: This is a retrospective review of a prospectively-maintained database of patients treated at the multi-disciplinary breast cancer clinic at the University of Louisville from 2003-2009. Patientswith unilateral pre-invasive and invasive adenocarcinoma who underwent mastectomy as primary surgical treatment for the involved breast with CPM were included. All information from surgical, medical and radiation oncology records were reviewed for this analysis. Results: A total of 107 patients are included in this analysis. The median age was 48 years (range 26-80). A previous history of breast cancer was noted in 8% of patients, all of whom received lumpectomy and whole-breast radiotherapy. A family history of breast cancer was identified in 46% of patients and 4% of patients possessed a germline BRCA mutation. Ninety-three percent of tumors were invasive. Evaluation of the pathological tumor (T) stage yielded 7% Tis, 48% T1, 36% T2, 3% T3, and 3% T4. Four percent of tumors were pathologically T0 after a complete response to neoadjuvant chemotherapy. Pathological node (N) staging yielded 56% N0, 23% N1, 14% N2, and 7% N3. Two percent of patients had distant metastasis at diagnosis. Twenty-two percent of tumors were negative for the estrogen, progesterone, and HER2/neu receptors (triple negative). Lobular carcinoma in situ was found in 10% of tumors. Five occult tumors were detected in the contralateral breast, of which 4 were carcinoma in situ and 1 was invasive mucinous carcinoma. With a median follow-up of 27 months (range 7-83), 9 treatment failures have been noted. Four patients failed locoregionally, 3 failed distantly, and 2 failed both locoregionally and distantly. Five patients have died of metastatic disease. No contralateral chest wall failures have occurred. Conclusions: CPM has become more popular over the past 6 years and patients present with a diverse array of clinical and pathological features. Occult disease in the contralateral breast is rare and was not encountered in our series. The pattern of failure is determined by the primary disease and the clinical utility of CPM therefore remains uncertain. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-14-15.
Abstract 3756: MiR-203 inhibits the proliferation and self-renewals of esophageal cancer stem-like cells by suppression stem renewal factor Bmi-1.
Authors: Xiying Yu, Xingran Jiang, Hongxia Li, Liping Guo, Wei Jiang, Shih-Hsin Lu
Journal: Cancer Research (2013)

Abstract Recent reports have shown that cancer stem-like cells exist in many malignancies and several stem cell-related gene products and miRNAs, such as Bmi-1 and miR-203, were identified as cancer stem-like cell regulators using gene microarray or sequencing analysis. Bmi-1 is essential for the self-renewal capacity of several types of normal stem cells and cancer stem-like cells while miR-203 is involved in stem cell self-renewal regulation. Previously, we used side population (SP) sorting to enrich cancer stem-like cells from esophageal squamous cell carcinoma (ESCC) cell line EC9706. Our results demonstrated that EC9706 SP cells have the same common features of cancer stem-like cells, such as the ability of self renewal, highly proliferation and tumorigenesis. In this study, we examined expression regulation of Bmi-1 and miR-203 in ESCC SP and none-SP (NSP) cells. Our results showed that, when compared with NSP cells, Bmi-1 was up-regulated and miR-203 was down-regulated in SP cells. During the differentiation from SP to NSP cells, the expression levels of Bmi-1 were gradually decreased, suggesting that Bmi-1 might be required for maintaining the ESCC SP cells. As sequence analysis revealed that the mRNA 3’UTR of Bmi-1 has a highly conserved binding site of miR-203, we overexpressed miR-203 in EC9706 cells using lentivirus mediated gene transduction. Overexpression of miR-203 (lenti-miR-203) resulted in a significant reduction of endogenous Bmi-1 protein levels in EC9706 cells. SP and NSP analyses revealed that the SP cell fraction markedly decreased in lenti-miR-203 cells. Lenti-miR-203 cells also showed significantly reductions of the colony formation, resistant to chemotherapeutic drug treatment and tumorigenicity in nude mice. Rescue experiments demonstrated that ectopic expression of Bmi-1 in lenti-miR-203 cells increased the SP fraction and restored cell proliferation. Taken together, these results indicated that stem renewal factor Bmi-1 is a direct target of miR-203. Regulation of Bmi-1 by miR-203 may play an important role in controlling cell proliferation and self-renewals of esophageal cancer stem-like cells. Citation Format: Xiying Yu, Xingran Jiang, Hongxia Li, Liping Guo, Wei Jiang, Shih-Hsin Lu. MiR-203 inhibits the proliferation and self-renewals of esophageal cancer stem-like cells by suppression stem renewal factor Bmi-1. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3756. doi:10.1158/1538-7445.AM2013-3756
Abstract 5087: UCSC Cancer Genomics Browser 2.0
Authors: Jingchun Zhu, Brian Craft, Teresa Swatloski, Kyle Ellrott, Mary Goldman, Christopher Wilks, Singer Ma, Christopher Szeto, Eric Collisson, David Haussler
Journal: Cancer Research (2012)

Abstract As the rate of cancer genomic information production has increased so has the task of managing the computational infrastructure required to host, visualize and analyze that data. The UCSC Cancer Genomics Browser (https://genome-cancer.ucsc.edu) provides a variety of tools to help researchers analyze their data. It includes sortable genomic heatmaps linked to patient clinical attributes that can be explored on demand. A user can run statistical tests between user defined groupings of samples, genomic signature evaluations, and toggle between chromosomal and custom gene sets views. The browser is linked to the UCSC Genome Browser; thus inheriting and integrating the Genome Browser's rich set of human biological and genetic data that enhances the interpretability of the cancer genomics information. UCSC Cancer Genomics Browser 2.0 has been released with drastically enhanced user. Other recent improvements in the Cancer Genomics Browser have been in response to the growing number of collaborative cancer analysis projects. Designed with the privacy issues that come along with patient data in mind, cancer browser accounts provide user-specific sessions, gene sets, genomic profiles, and user-specific data tracks controls. In addition to the public portal, the Cancer Genomics Browser also supports projects that require secured access control. The system hosts results from TCGA, SU2C (Stand Up To Cancer), LINCS (Library of Integrated Network-based Cellular Signatures), GEO (Gene Expression Omnibus) and the ISPY trials along with information from individual labs. Researchers that have been authenticated to multiple projects can see the results from all of their projects in a single page. The other aspect of working with multiple collaborative cancer projects is the issue of properly defining data interchange formats. For the Cancer Genome Browser we have created a specification called cgData, which will be used by UCSC to consolidate various types of information from TCGA. cgData is a designed to provide the variety of file formats that are required to describe the heterogeneous data required for the browser. Formats for defining expression matrices, genomic probe definitions, clinical feature data, mutation information and sample mapping have all been specified to enable rapid integration of new data into the Cancer Genome Browser. This format is being developed in collaboration with partners from SU2C and LINCS, and utilities to convert The Broad Institutes TCGA Firehose analysis and MSKCC cBio portal information have already been developed. The publicly available data is organized into downloadable releases on a monthly basis. 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 5087. doi:1538-7445.AM2012-5087
Blunt Trauma Soft-Tissue Uptake on Skeletal Scintigraphy
Authors: Clayton J. Frater, Walter Haindl
Journal: Clinical Nuclear Medicine (2003)

Muscle and soft-tissue uptake have been described numerous times in the literature in patients undergoing Tc-99m methylene diphosphonate skeletal scintigraphy following trauma. Many of these traumas range from electrical burns, intramuscular injections, sports-related trauma, and overexercising, to actual physical damage resulting in superficial bruising and skin discoloration. In this case the patient presented with continuing low back pain after falling down some stairs. Although the scan was essentially normal for bony trauma, subtle soft-tissue uptake was detected that was enhanced with the addition of single photon emission computed tomographic imaging and surface rendering.
Abstract 190: Targeting ceramide and endoplasmic reticulum-stress in vitamin E induced apoptosis in human breast cancer cells
Authors: Archana Gopalan, Weiping Yu, Bob Sanders, Kimberly Kline
Journal: Cancer Research (2011)

Abstract Vitamin E consists of eight plant-derived forms classified as tocopherols (α, β, Δ, γ) and tocotrienols (α, β, Δ, γ) which have a chromanol ring and a saturated and unsaturated aliphatic side chain, respectively. The anti-cancer actions of tocopherols and tocotrienols are limited to the gamma and delta forms. Here, we report that both γ-tocopherol (γT) and γ-tocotrienol (γT3) display potent anti-cancer actions with γT3 being more potent. Both forms target similar pro-apoptotic and anti-apoptotic pathways. γT and γT3 induced apoptosis in human breast cancer cells by enhancing death-receptor DR5 mediated activation of caspase-8 and mitochondria dependent caspase-9, as well as by activating ER-stress markers: GADD153/ C/EBP homologous protein (CHOP), GRP-78, ATF-4 and eIF2α. JNK and CHOP are involved in DR5 mediated apoptosis triggered by both vitamin E forms. γT and γT3 decreased protein levels of anti-apoptotic factors c-FLIP, BCl-2 and survivin. Since ceramide is a known upstream inducer of ER-stress and downstream mediator of death receptor apoptotic pathway mediators, treatments with γT and γT3 were conducted in the presence of specific inhibitors of sphingomyelin hydrolysis, de novo ceramide pathways and ER-stress in order to distinguish between the pathways modulated by the vitamin E forms. Data show that both γT and γT3 induced apoptosis via activation of sphingomyelin hydrolysis and the de novo ceramide pathways; however, activation of the ER-stress pathway contributed to apoptosis induced by γT3 only. Taken together, our data suggest that γT3s more potent apoptotic effects in comparison to γT are due to the ability of γT3 to activate ER stress pathways. This better understanding of the anti-cancer properties and mechanistic actions by these two natural occurring agents in vitro provides the necessary impetus to test them in combination with other known anti-cancer agents in pre-clinical xenograft studies to identify novel and safer therapeutic strategies. Research funded by The Clayton Foundation for Research. 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 190. doi:10.1158/1538-7445.AM2011-190
OP0112 Abatacept Treatment Reduces Disease Activity in Early Primary Sjögren’s Syndrome (Phase II Open Label Asap Study)
Authors: P. Meiners, A. Vissink, F. Kroese, F. Spijkervet, E. Haacke, W. Abdulahad, N. Sillevis Smitt-Kamminga, E. Brouwer, S. Arends, H. Bootsma
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Abatacept, a selective co-stimulation modulator of T lymphocytes, could be a new treatment option for primary Sjögren’s syndrome (pSS). <h3>Objectives</h3> To assess short-term efficacy and safety of abatacept treatment in early pSS patients. <h3>Methods</h3> 15 pSS patients (12 female, 3 male) were included in the open-label ASAP (Active Sjögren Abatacept Pilot) study. All patients met the revised AECG criteria. Disease duration was &lt;5 years. DMARDs or corticosteroids were discontinued at least 1 month before baseline. Patients were biological DMARD naïve. All patients were treated with 8 abatacept infusions (≈10 mg/kg of body weight) administered intravenously on days 1, 15, and 29 and then every 28 days for 5 months. Follow-up was conducted at 4, 12, 24 (on treatment), 36, and 48 weeks (off treatment). Follow-up data up to 24 weeks are available for all patients. Disease activity was assessed with the EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) and Disease Activity Index (ESSDAI). Other objective and laboratory variables included stimulated whole saliva, rheumatoid factor (RF), IgG, and T and B cell counts. Generalized estimating equations were used to analyse parameters over time. <h3>Results</h3> Median age and disease duration were 43 years and 11 months. Significant improvements during treatment were found for ESSPRI and ESSDAI (Fig.1). Furthermore, RF levels decreased significantly from 43 kIU/l at baseline to 28 kIU/l at week 24, and IgG levels dropped from 20.2 g/l to 16.5 g/l. Absolute numbers of T- and B-cells decreased slightly (&lt;10%). Stimulated whole saliva remained stable. Abatacept treatment was well tolerated. No deaths, serious adverse events or serious/opportunistic infections were seen. <h3>Image/graph</h3> <h3>Conclusions</h3> The promising interim results of this first open-label pilot study indicate that abatacept treatment is well tolerated, safe and presents a clinically meaningful improvement of disease activity and laboratory parameters. It is worthwhile to further explore the efficacy and safety of abatacept in future trials. <h3>Acknowledgements</h3> <i>Supported by an unrestricted grant and study medication by BMS, France</i> <h3>Disclosure of Interest</h3> None Declared
Selective Tri-Nucleotide Spacers Modulate the Regulatory Potential of Estrogen Response Elements.
Authors: C. Kallen, D. Yang, N. Sidell
Journal: Cancer Research (2009)

Abstract Estrogens bound to Estrogen Receptors (ERs) play critical roles in breast cancers through their binding to certain DNA motifs (i.e. estrogen response elements or EREs) in the promoters of target genes to regulate their transcriptional activity. The consensus ERE has the 15 base sequence AGGTCAnnnTGACCT where nnn are known as the tri-nucleotide spacer. The base specificity or sequence of this spacer is thought to be unimportant in terms of its effect on ERα-ERE binding affinity or transactivation efficiency. In the present experiments, whole genome sequence analysis of ERα-DNA binding sites was performed in MCF-7 breast cancer cells using CHIP-on-chip assays to determine frequency variations in EREs that bind ERα. Here, we present evidence that ERα binds to widely variant ERE sequences, both in terms of half-site specificity and tri-nucleotide spacer identity. Overall, our analysis indicated that whole genome ERα-ERE binding highly favored specific C(A/T)G enriched tri-nucleotide spacers, suggesting some evolutionary advantage to this three base configuration. To address this question in MCF-7 cells, we designed consensus EREs containing different nnn spacers (CTG, GCC, TTT) to test as binding probes in Electrophoretic Mobility Shift Assays and as enhancer elements in luciferase reporter vectors. Our results indicated differences in the ERα-ERE binding affinity depending on the nnn spacer sequence with the order of affinity being CTG &amp;gt; GCC &amp;gt; TTT. To determine the potential functional significance of the tri-nucleotide spacers, luciferase reporter assays in MCF-7 cells were performed. Results showed the same dependency on the sequence of the nnn spacer to induce luciferase activity in response to estrogen treatment (CTG&amp;gt;GCC&amp;gt;TTT). These experiments indicate that the identity of the three base spacer elements in the ERE are important for influencing ERα-ERE interactions and functional activity. These data support the results of the whole genome CHIP-on-chip analysis and suggest that increased frequency of ERα binding to ERE motifs with C(A/T)G spacers is due to preferential binding characteristics resulting in efficient transactivation of estrogen target genes. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3179.