tbuckley/cabot-search huggingface dataset:
SAT0386 Data-Driven Cluster Analysis of Joint Swelling and Tenderness in A Large Psoriatic Arthritis Cohort – Comparison with CASPAR Classification, Moll &amp; Wright Subtypes, and Clinical Response to TNF Blockade
Authors: D. Stekhoven, A. Scherer, P.M. Villiger, B. Möller
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Psoriatic arthritis (PsA) shows the largest complexity in joint involvement among all inflammatory types of arthritis. <h3>Objectives</h3> We aimed at comparing a feasible number of data-driven joint involvement (JI) groups in the Swiss Clinical Quality Management (SCQM) PsA cohort with the classical subtypes of PsA as described by Moll &amp; Wright (M&amp;W). Also, we compared these new PsA subgroups in their clinical response to TNF-blockade, the current gold standard of disease modification in respect of structural damage. <h3>Methods</h3> By December 1st 2013, we included all 1380 patients in the SCQM registry with PsA diagnosis. Hierarchical clustering was applied to generate distinct groups of patients based only on their tender or swollen joint involvement. The robustness of clustering was tested by comparing swollen (SJ) and tender joint (TJ) clusters, and by repeated clustering with different linkage methods. Analyses were repeated in the subgroup of 872 PsA patients fulfilling the CASPAR classification criteria. <h3>Results</h3> Ward9s Minimum Variance method for clustering gave the most distinguished clusters and will be reported in the following results. In both SJ and TJ four clusters were found characterizing oligoarticular, hand or foot predominant, and polyarticular features (Fig. 1). On the individual patient level, about one third of joints were affected in a symmetric manner. Assignment of patients to the same clusters in SJ and TJ varied between 85% (oligoarticular) to 17% (polyarticular). In the following, only SJ results are reported. Most patients assigned to the oligoarticular cluster were also of the oligoarticular M&amp;W subtype (78%). The rest of patients in the oligoarticular cluster were in the symmetric (11%) or DIP (2%) M&amp;W subtypes or were not assignable to these subtypes (9%). In the polyarticular cluster, MCP and PIP joints were more frequently involved than DIP joints, but osteoproliferation, typically juxta-articular to DIP joints, was also overrepresented (49%, p&lt;0.001). Dactylitis was most prevalent in cluster D, but clinical improvements upon TNF blockade were similar among the groups. <h3>Conclusions</h3> We identified a small but highly characteristic cluster of patients with more extended joint, bone and skin involvement, but all obtained clusters were similar with regard to response to TNF-blockade. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4047
Wire-guided endoscopic snare resection of a choledochocele-associated villous adenoma
Authors: J. Park, J. Moon, H. Kim, H. Choi, J. Kang, H. Kim, B. Ko, Y. Cho, M. Lee, C. Shim
Journal: Endoscopy (2009)

Adenomas arising in a choledochocele are usually resected surgically because they are difficult to completely remove endoscopically and they are associated with a high malignancy potential [1] [2]. We successfully performed an endoscopic snare resection for choledochocele-associated villous adenoma with high-grade dysplasia.
SP0088 The genetics of myositis - recent insights from autoimmune diseases and statins
Authors: R. Cooper
Journal: Annals of the Rheumatic Diseases (2013)

It is increasingly clear that IIM disease susceptibility is statistically highly associated with genes at HLA, which likely interact with environmental factors to trigger disease. IIM may be classified by “traditional” subtype (PM, DM and IBM), but classification by myositis-specific/associated antibody (MSA/MAA) status is increasingly advocated, as the differential presence of these antibodies is predictive of an individual’s disease phenotype within the IIM spectrum. Moreover, the MSA/MAA detected in any individual IIM sufferer is predictable from that individual’s genotype at HLA. This close association between HLA genotype and IIM subtype, including MSA/MAA status, suggests that HLA genotype is somehow involved in determining overall IIM phenotype. This may mean that, when an IIM is environmentally triggered, the sufferer’s disease phenotype is somehow predetermined by their genotype status at HLA. The notion that IIM phenotype is linked mechanistically to HLA genes is however speculative, and currently unproven. Recent research has progressed our understanding of immunogenetics, and its potential implications for differential disease expression including circulating autoantibodies in IIM as well as in other autoimmune diseases. The remit of this presentation is to use the results of these recent immunogenetic studies in IIM and other autoimmune diseases to explore the hypothesis that HLA gene:gene and HLA gene:envioronment interactions may play important roles in determining disease susceptibility, phenotype and treatment outcomes in IIM and in other autoimmune diseases. <h3>Disclosure of Interest</h3> None Declared
Inactivating Mutations in the Gene for Thyroid Oxidase 2 (<i>THOX2</i>) and Congenital Hypothyroidism
Authors: José C. Moreno, Hennie Bikker, Marlies J.E. Kempers, A.S. Paul van Trotsenburg, Frank Baas, Jan J.M. de Vijlder, Thomas Vulsma, C. Ris-Stalpers
Journal: New England Journal of Medicine (2002)

Several genetic defects are associated with permanent congenital hypothyroidism. Immunologic, environmental, and iatrogenic (but not genetic) factors are known to induce transient congenital hypothyroidism, which spontaneously resolves within the first months of life. We hypothesized that molecular defects in the thyroid oxidase system, which is composed of at least two proteins, might be involved in the pathogenesis of permanent or transient congenital hypothyroidism in babies with defects in iodide organification, for which the oxidase system is required.
Abstract 1159: Identification of potential miRNA biomarkers for breast cancer using TaqMan® Pri-miRNA assays
Authors: Yu Liang, Athina Markoy, Evi Lianidou
Journal: Cancer Research (2011)

Abstract Identification of cancer biomarkers depends on measuring the differential genotypes and phenotypes between normal and disease tissues. However, cancer is characterized by accumulation of genetic lesions and heterogeneity, and hence great efforts need to be invested to distinguish driver versus passenger abnormalities. Several strategies have been employed to achieve the distinction, including conservation of genetic lesions between mouse models and human diseases, gain of copy number/amplification, deletion/loss of heterogeneity, and epigenetic alterations. Redundancy of some microRNA (miRNA) genes has been an interesting finding and its biological significance is not clear. These redundant miRNA loci have different genomic locations and are transcribed independently, and yet are processed into identical mature miRNA, and these loci are annotated as -1, -2, -3, etc, following the miRNA gene name. Selective expression of these loci could be a regulatory strategy to control expression of other genomically associated genetic elements that are critical to the disease processes, while the required level of mature miRNA can still be maintained by leveraging the redundancy. The proof-of-principle of this rationale was to compare between normal breast and breast cancer cell lines the expression of miRNA genes that have multiple loci and are associated with other genetic elements such as other miRNA genes within the same clusters or their host protein-coding/non-coding genes. This investigation narrowed down to mir-100 gene that is clustered with let-7a-2 gene, both of which lost expression completely in three luminal-type breast cancer cell lines but not in one basal-type cell line and normal breast, whereas expression from let-7a-1 and let-7a-3 remains unchanged between normal breast and cell lines tested. Loss of mir-100 and let-7a-2 expression appears to be caused at least by loss of one copy or both copies of these two loci. Deletion of mir-100 locus can also be detected in clinical specimens. These results suggest that this method might effectively distinguish driver versus passenger differentially expressed genes. 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 1159. doi:10.1158/1538-7445.AM2011-1159
Abstract P3-05-09: The role of TGF-beta receptor type 3 in breast cancer progression
Authors: B Jovanovic, WJ Ashby, A Zijlstra, JA Pietenpol, HL Moses
Journal: Cancer Research (2012)

Abstract Breast cancer is a diverse group of diseases. Gene expression profiling has identified luminal A, luminal B, Her2-like, Normal breast-like and Basal-like as major classifications of breast cancer diseases. These correlate to the overall patient survival with the basal-like subtype, clinically termed as triple-negative breast cancers (TNBC), demonstrating the poorest overall outcome. The poor patient outcome is primarily due to absence of hormonal receptor targets ER, PR and HER2 which are the major drug-targets for currently available therapies. Considering that TNBC lacks well-defined molecular targets, our group pursued extensive genomic molecular and biological analysis of over 500 tumor tissues from TNBC patients. Ultimately, this led to the discovery of six, TNBC subtypes; among which are Mesenchymal-Stem Like (MSL) and Mesechymal (M). These two subtypes share a unique biological driver, the TGF-beta pathway. To gain insight into the role of the TGF-β pathway signaling in TNBC we have performed gene expression analysis on all six TNBC subtypes. A major finding was that among all TGF-β pathway-associated genes, TGF-beta receptor type 3 (TBR3) is most differentially expressed in MSL and M tumor subtypes of TNBC. Based on these findings, we are hypothesizing that TBR3 is required for maintenance of tumorigenicity in MSL and M subtypes of the triple-negative breast cancer. In order to test our hypothesis we have screened 15 TNBC cell lines for both RNA and protein levels of TBR3 and validated that TBR3 is differentially expressed in M and MSL subtypes. Furthermore, we have manipulated TBR3 expression in M and MSL TNBC cell lines and tested their ‘biologies’ using both an in vitro and in vivo model systems. Preliminary results indicate that upon silencing TBR3 expression, cell motility as well as ability to cluster together in 3D culture system is significantly changed. In addition, our xenograft mouse model also demonstrated a significant change in tumor onset and growth. We are interested in validating the prognostic and functional contribution of TBR3 to the breast cancer progression. The results of this study will provide insight into the potential use of the TGF-β signaling axis for prognostic or therapeutic utility in breast cancer patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-05-09.
Belling the cat: Why reuse theory is not enough
Authors: Oscar Vilarroya
Journal: Behavioral and Brain Sciences (2010)

Abstract I agree with Anderson's approach to reuse theories. My main concern is twofold. Anderson assumes certain nomological regularities in reuse phenomena that are simply conjectures supported by thin evidence. On the other hand, a biological theory of reuse is insufficient, in and of itself, to address the evaluation of particular models of cognition, such as concept empiricism or conceptual metaphor.
IT-15 * DELTA-24-RGDOX: TARGETING CO-STIMULATORY IMMUNE CHECKPOINT PROTEINS WITH ONCOLYTIC ADENOVIRUSES
Authors: H. Jiang, F. Lang, X. Fan, J. Gumin, L. Bover, K. Clise-Dwyer, C. Toniatti, K. Ruisaard, C. Conrad, L. Vence, C. Gomez-Manzano, J. Fueyo
Journal: Neuro-Oncology (2014)

OX40 ligand (OX40L), the ligand for OX40 on activated CD4+ and CD8+ T cells, has adjuvant properties for establishing effective T-cell immunity against cancer. The hypothesis of this study is that oncolytic viruses expressing OX40L will stimulate tumor-specific T cells by the OX40L-OX40 engagement. We will also test whether Delta-24-RGD induces DAMPs, and systemic immunity against the tumor. To test the hypothesis we modified Delta-24-RGD to express the OX40 ligand during replication, the new virus was called Delta-24-RGDOX. Flow-cytometry analyses of human glioma U-87MG and mouse glioma GL261 cells infected with Delta-24-RGDOX detected the expression of OX40L by 48h after infection. Importantly, infection of glioma cells with Delta-24-RGDOX resulted in the production of DAMPs (The damage-associated molecular pattern high-mobility group box 1, calreticulin, HSP70 and HSP90 proteins) as assessed by western blot and ELISA analyses, indicating immunogenic cell death. In addition, using a syngeneic animal model, we showed that intratumoral injection of Delta-24-RGDOX caused infiltration of innate and adaptive immune cells, instigating a Th1 immunity at the tumor site which resulted in specific anti-glioma immunity, shrunken tumor and prolonged animal survival. Importantly, Delta-24-RGDOX treatment showed superior efficacy that the treatment with Delta-24-RGD (28.5 vs. 17 days; P< 0.0001). Moreover, we showed that splenocytes from mice treated with both therapies were stimulated against infected and non-infected GL261 cells in a significantly greater degree than splenocytes of mice treated with the combination of Delta-24-RGD and OX40 antibodies (P<0.001). Consistent with the anti-tumor immune hypothesis, treatment with Delta-24-RGDOX did not prolong the life of immunosuppressed mice bearing intracranial GL261 tumors (P>0.01). These results support the concept that the immune-mediated anti-gliomas effects of Delta-24-RGD can be greatly enhanced by Delta-24-RGD-OX40L and warrant the clinical testing of the new immune-targeted adenovirus in patients with malignant gliomas.
Abstract 2197: p53-dependent expression of the fluorouracil (5-FU) catabolic enzyme dihydropyrimidine dehydrogenase (DPD) in mouse liver.
Authors: Prashanth R. Gokare, Niklas Finnberg, Joshua Allen, Jenny Dai, Wafik El-Deiry
Journal: Cancer Research (2013)

Abstract Fluorouracil (5-FU) a commonly used drug in the treatment of cancer is hampered by a short unpredictable plasma half-life, which complicates dose modulation to minimize toxicity and improve efficacy of 5-FU treatment. Strategies to improve on the unfavorable pharmacokinetic properties of 5-FU, currently under clinical trial, involve targeting of the catabolic enzyme dihydropyrmidine dehydrogenase (DPD).This requires understanding the mechanisms regulating the expression of DPD and the inducibility of 5-FU catabolism, which is inadequately investigated. By performing in silico analysis we were able to identify putative p53 binding sites in the proximity of the dihydropyrimidine dehydrogenase gene (DPYD) and confirm by chromatin immunoprecipitation (ChIP) that p53 increasingly locates to a binding site (about 1.8 ± 0.05 fold over untreated control) downstream of DPYD (P53DBS) following a single IV bolus of 5-FU (150 mg/kg bw) in mouse liver. Indeed, DPYD mRNA increased by 1.8 fold and protein by 1.8 fold (P&amp;lt; 0.0005) respectively in a time- and p53-dependent manner in the liver of treated with 5-FU. Our ongoing studies are focused on assessing p53-dependent regulation of DPD-activity and the resulting change in 5-FU bioavailability We suggest that p53 can regulate an important step of pyrimidine-catabolism and targeting p53 in the context of 5-FU therapy of malignancies carrying p53 mutations may be another strategy to improve treatment efficacy. Citation Format: Prashanth R. Gokare, Niklas Finnberg, Joshua Allen, Jenny Dai, Wafik El-Deiry. p53-dependent expression of the fluorouracil (5-FU) catabolic enzyme dihydropyrimidine dehydrogenase (DPD) in mouse liver. [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 2197. doi:10.1158/1538-7445.AM2013-2197
Home and work place evaluation in contact tracing
Authors: Raquel Duarte, Maria Neto, Aurora Carvalho, Henrique Barros
Journal: European Respiratory Journal (2011)

In an urban city, a decision was taken in 2004 to modify tuberculosis (TB) contacts screening strategy from targeting only close contacts identified by interview with the index case (the national policy) to a screening strategy involving home and work visit.  The present study compares TB contact-tracing during the periods 2001 to 2003 and 2004 to 2006 trying to capture how the new contact tracing strategy addressed the three main questions: (i) Does this strategy increase TB screening compliance? (ii) Does it identify more at-risk contacts? (iii) Does it result in more TB cases being prevented?  Home and work visit allowed to identify more at risk contacts (8.4/index case) than the interview (2.5/index case); to improve compliance (87.3% of the identified contacts were screened, compared to 67.6%). More cases of active TB and LTBI cases were detected (1.4/index case compared with 0.75/index case) and prevented more TB cases in the future.  The newly implemented contact-screening program with home and work place evaluation of active TB patients, improved compliance to screening procedures, identified more at-risk contacts and should allow us to prevent more TB cases in the future.
CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis
Authors: Bob Olsson, Ronald Lautner, Ulf Andreasson, Annika Öhrfelt, Erik Portelius, Maria Bjerke, Mikko Hölttä, Christoffer Rosén, Caroline Olsson, Gabrielle Strobel, Elizabeth Wu, Kelly Dakin, Max Petzold, Kaj Blennow, Henrik Zetterberg
Journal: The Lancet Neurology (2016)
Researchers Get Creative in Solving MoAb Problems
Authors: M. Patlak
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Researchers Get Creative in Solving MoAb Problems Get access Margie Patlak Margie Patlak Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 10, 20 May 1992, Pages 748–750, https://doi.org/10.1093/jnci/84.10.748 Published: 20 May 1992
Congress Decides NIH Funding Level
Authors: D. Tisevich
Journal: JNCI Journal of the National Cancer Institute (1996)

News News have a higher risk of aggressive prostate cancer is exciting, but he cautioned that for now, 'It's far too preliminary to use this information clinically."For example, he said it is too early for physicians in practice to give high-risk men a blood test for CAG repeats as a marker of prostate cancer risk, although such a test may ultimately become available.
REST FLOW RATE, NOT STROKE VOLUME, IS A BETTER DISCRIMINATOR OF TRUE VERSUS PSEUDOSEVERE SEVERE AORTIC STENOSIS: IMPLICATIONS FOR STRESS ECHOCARDIOGRAPHY AND FOR THE ROUTINE ASSESSMENT OF AORTIC STENOSIS SEVERITY
Authors: Navtej S. Chahal, Maria Drakopoulou, Ana Gonzalez, Alison Duncan, Rajdeep S. Khattar, Roxy Senior
Journal: Journal of the American College of Cardiology (2015)
Efficacy of Pneumococcal Vaccine in High-Risk Patients
Authors: Michael S. Simberkoff, Anne P. Cross, Mohamed Al-Ibrahim, Aldona L. Baltch, P.Jan Geiseler, Jeffrey Nadler, Alma S. Richmond, Raymond P. Smith, Gerald Schiffman, Donald S. Shepard, John P. Van Eeckhout
Journal: New England Journal of Medicine (1986)

We conducted a randomized, double-blind, placebo-controlled trial to test the efficacy of the 14-valent pneumococcal capsular polysaccharide vaccine in 2295 high-risk patients (patients with one or more of the following: age above 55 years and the presence of chronic cardiac, pulmonary, renal, or hepatic disease, alcoholism, or diabetes mellitus). Seventy-one episodes of proved or probable pneumococcal pneumonia or bronchitis occurred among 63 of the patients (27 placebo recipients and 36 vaccine recipients). Vaccine-serotype Streptococcus pneumoniae strains were recovered in association with 11 infections in the placebo group and 14 infections in the vaccine group. Pneumococcal infections occurred most frequently among patients with chronic pulmonary, cardiac, or renal diseases. Among vaccine recipients who subsequently had vaccine-type pneumonia or bronchitis, the majority did not make or sustain serum antibodies against their infecting organism in concentrations that were twice as high as the base-line values, or more than 400 ng of antibody nitrogen per milliliter, although their base-line levels were higher than those in subjects in whom infection did not develop. We were unable to demonstrate any efficacy of the pneumococcal vaccine in preventing pneumonia or bronchitis in this population. Our data suggest that chronically ill patients, who are most susceptible to infection, may have an impaired immune response to the pneumococcal vaccine.
Feasibility of Using Autologous Transplantation to Evaluate Hematopoietic Stem Cell-Based Gene Therapy Strategies in Transgenic Mouse Models of Human Disease
Authors: Cindy L. Miller, Suzan Imren, Jennifer Antonchuk, Christian Kalberer, Mary E. Fabry, Ronald L. Nagel, R.Keith Humphries, Connie J. Eaves
Journal: Molecular Therapy (2002)

Histoincompatibility between murine donors and recipients of bone marrow (BM) transplants reduces engraftment, and this compromises assessment of hematopoietic stem cells (HSCs) in certain transgenic mice. To study HSCs in the S+S–Antilles mouse model of human sickle cell disease (SCD), we developed an autotransplant protocol. Initial experiments showed no differences between S+S–Antilles mice and normal C57BL/6 (+/+) mice in their radiosensitivity or baseline hematopoietic progenitor numbers. The kinetics of red blood cell (RBC) replacement post-transplant in +/+ recipients of mixtures of transgenic and +/+ BM cells also showed no competitive advantage of the +/+ cells. BM cells were then aspirated from mice 4 days after 5-fluorouracil treatment, transduced with a green fluorescent protein (GFP)-encoding retrovirus, and transplanted into the same recipients that, just before transplant, were irradiated with 800 cGy. We subsequently detected high levels of GFP+ RBCs (21–79%) and white blood cells (WBCs; 35–88%) in the blood for 11 months and showed that transduced HSCs regenerated in the primary mice also repopulated secondary mice. These findings provide a generally applicable protocol for performing autotransplants in mice and forecast the potential utility of this approach in assessing HSC-based gene therapy protocols in transgenic mouse models of many human diseases. Histoincompatibility between murine donors and recipients of bone marrow (BM) transplants reduces engraftment, and this compromises assessment of hematopoietic stem cells (HSCs) in certain transgenic mice. To study HSCs in the S+S–Antilles mouse model of human sickle cell disease (SCD), we developed an autotransplant protocol. Initial experiments showed no differences between S+S–Antilles mice and normal C57BL/6 (+/+) mice in their radiosensitivity or baseline hematopoietic progenitor numbers. The kinetics of red blood cell (RBC) replacement post-transplant in +/+ recipients of mixtures of transgenic and +/+ BM cells also showed no competitive advantage of the +/+ cells. BM cells were then aspirated from mice 4 days after 5-fluorouracil treatment, transduced with a green fluorescent protein (GFP)-encoding retrovirus, and transplanted into the same recipients that, just before transplant, were irradiated with 800 cGy. We subsequently detected high levels of GFP+ RBCs (21–79%) and white blood cells (WBCs; 35–88%) in the blood for 11 months and showed that transduced HSCs regenerated in the primary mice also repopulated secondary mice. These findings provide a generally applicable protocol for performing autotransplants in mice and forecast the potential utility of this approach in assessing HSC-based gene therapy protocols in transgenic mouse models of many human diseases.