tbuckley/cabot-search huggingface dataset:
OP0215 Bias in effect size of systemic lupus erythematosus susceptibility loci across europe
Authors: E. Alonso-Perez, A. Gonzalez
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> More tan 30 reproducible SLE susceptibility loci have been identified in the last years. Some of these loci are specific of particular ethnic groups, like <i>PXK</i> or <i>FCGR2A</i>, due to unknown causes<sup>1</sup>. Independently, it has become clear that there are gradients of prevalence of some SLE clinical features among Europeans<sup>2,3</sup>, and it is known that there are frequency clines of polymorphisms in the Europeans along a dominant North-South axis<sup>4</sup>. Therefore, we have hypothesized that there could be heterogeneity in the effect sizes of SLE loci among Europeans. <h3>Objectives</h3> We aimed to know if the effect size of the SLE susceptibility loci varies across Europe. <h3>Methods</h3> European SLE patients, 1742, and ethnically matched healthy controls, 2101, were recruited at 17 centres from 10 different countries. Only individuals with uniform self-reported ancestry from the country of origin were included. In addition, they were genotyped for top ancestry informative markers and for 25 SLE susceptibility loci. The results were used to compare association effect sizes between the Central and Southern European subgroups. <h3>Results</h3> Twenty of the 25 loci showed significant association with SLE in our samples. There was a significant bias to larger effect sizes in the Southern subgroup with 15/20 associated SNPs showing this trend (P=0.019), two of them with significant differences. There was also a larger mean O.R. of the 20 SNPs (1.46 vs.1.34; P=0.02) in patients from the South than from Central Europeans., as well as, a larger difference in the number of risk alleles between SLE patients and controls (2.06 vs. 1.63; P=0.027). This bias was accompanied by a lower number of SLE risk alleles in the Southern subjects, both patients and controls, being the difference more marked between the controls (12.0 <i>vs.</i> 12.8; P=1.1×10<sup>-8</sup>) than between the Southern and Central European patients (14.0 <i>vs.</i> 14.4; P=0.016). <h3>Conclusions</h3> Our study has shown a bias in effect sizes of the SLE susceptibility loci towards a stronger association in Southern Europeans relative to Central Europeans. This bias is related with a lower frequency of risk alleles in the Southern subgroup, with a more marked difference in healthy controls than in SLE patients. These results have implications for the design and interpretation of genetic studies and for the understanding of the SLE genetic structure. They also suggest that selective forces have shaped the genetic epidemiology of SLE differentially in Europeans and reinforce the need to investigate the proposed interplay between infection resistance and susceptibility to autoimmunity. <h3>References</h3> Han JW, et al. Nat Genet. 2009;41:1234-7 Chung SA, et al. Arthritis Rheum. 2009;60:2448-56 Alonso-Perez E, et al. PLoS One. 2011;6:e29033 Seldin MF, et al. PLoS Genet. 2006;2:e143 <h3>Disclosure of Interest</h3> None Declared
SEVERE AORTIC STENOSIS CAUSES BIVENTRICULAR DYSFUNCTION DEMONSTRATED BY TWO DIMENSIONAL AND THREE DIMENSIONAL GLOBAL LONGITUDINAL STRAIN USING TRANSTHORACIC ECHOCARDIOGRAPHY
Authors: Koya Ozawa, Nobusada Funabashi, Hiroyuki Takaoka, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2015)
Selective Bladder Preservation by Combination Treatment of Invasive Bladder Cancer
Authors: Donald S. Kaufman, William U. Shipley, Pamela P. Griffin, Niall M. Heney, Alex F. Althausen, J.T. Efird
Journal: New England Journal of Medicine (1993)

For patients with invasive bladder cancer the usual recommended treatment is radical cystectomy, although transurethral resection of the tumor, systemic chemotherapy, and radiotherapy are each effective in some patients. We sought to determine whether these treatments in combination might be as effective as radical cystectomy and thus might allow the bladder to be preserved and the cancer cured.
Effect of Bile Infusion on the Dog Kidney
Authors: Cemalettin Topuzlu, William M. Stahl
Journal: New England Journal of Medicine (1966)

TRADITIONALLY, the surgeon approaches the jaundiced patient with extreme care. His attitude arises from the high postoperative morbidity and mortality in jaundiced patients undergoing operations that otherwise carry little risk.1 In more than 50 per cent of such patients who die after surgery death has been due to renal failure and uremia. Almost invariably hypotension has occurred during the clinical course. Pathological studies of kidneys from patients dying of renal failure while jaundiced have shown a vacuolization of the tubular cells, suggestive of direct renal damage. Moreover, hyperbilirubinemia has appeared to make the kidney more susceptible to ischemic damage.2 Infusion . . .
131I Abnormal Uptake by the Thyroid Bed From Zuckerkandl Tubercle Diagnosis by 131I SPECT/CT
Authors: Joji Kawabe, Shigeaki Higashiyama, Kohei Kotani, Naoyoshi Onoda, Susumu Shiomi
Journal: Clinical Nuclear Medicine (2014)

After thyroid remnant ablation following total thyroidectomy for thyroid cancer, 131I SPECT/CT revealed 131I uptake, regarded as thyroid bed uptake on planar images, in the anterior cervical region. On SPECT/CT, the 131I uptake focus appeared at the esophagus, suggesting esophageal invasion. No esophageal invasion had been recognized intraoperatively, and no residual uptake was detected by 131I scintigraphy evaluating therapeutic effects 3 months after ablation. Preoperative CT revealed a retrotracheal space portion extending from the normal thyroid with the same density, suggesting Zuckerkandl tubercle. Abnormal uptake on SPECT/CT was deemed Zuckerkandl tubercle-derived thyroid bed uptake.
Abstract 2091: Ultrasensitive detection of mutations in the androgen receptor gene by ICE COLD-PCR
Authors: Yanggu Shi, Courtney Cubrich, Stephanie Veys, Katherine Richardson, Benjamin Legendre, Rui Lin, Grant Wu, Phil Eastlake
Journal: Cancer Research (2012)

Abstract The Androgen Receptor plays an important role in prostate cancer, androgen-dependent (AD) and androgen-independent (AI) disease progression. Anti-androgen therapies are the hallmark of prostate cancer treatment; however spontaneous AR mutations are often detected in hormone-refractory, androgen-ablated and metastatic tumors. ICE COLD-PCR (Improved &amp; Complete Enrichment CO-amplification at Lower Denaturation temperature) is a technology that preferentially enriches mutant DNA sequences in an excess of wild-type DNA through selective amplification of the mutant DNA population using an oligonucleotide complementary to wild-type sequence (RS-oligo). This RS-oligo prevents PCR amplification of wild-type sequences while allowing amplification of DNA containing any mutation covered in the RS-oligo region. We have developed an ICE COLD-PCR assay for the enrichment of mutations in the Androgen Receptor including the AR H875R, H875Y and T878A mutations. The mutant-enriched DNA was then analyzed by standard Sanger DNA sequencing. The analytical sensitivity for the ICE COLD-PCR assay was 1 in 10,000 (0.01%) for all the mutations, compared to 20% limit of detection by standard Sanger sequencing. The ICE COLD-PCR assay developed here provides a means to detect low level mutations in the Androgen Receptor and thus will provide a valuable methodology for the early diagnosis, treatment guidance, outcome prediction and relapse monitoring of prostate cancer. 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 2091. doi:1538-7445.AM2012-2091
DEGENERATIVE VERSUS FUNCTIONAL MITRAL REGURGITATION IN PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT FOR SEVERE AORTIC STENOSIS
Authors: James M. Ouzan, Byan Kindya, Israel Gotsman, Vasilis Babaliaros, Erhan Gonen, Bradley Leshnower, Eren Karayel, James Stewart, Ronen Beeri, Chandan Devireddy, Hina Ahmed, Haim Danenberg, Eric Sarin, Dan Gilon, Robert Guyton, Chaim Lotan, Stamatios Lerakis, Vinod Thourani, Peter Block, Kreton Mavromatis
Journal: Journal of the American College of Cardiology (2016)
Abstract 2076: Mammary stem cell-like miRNA expression and relation to cancer
Authors: Eylem Aydogdu, Luisa Helguero, Lars-Arne Haldosen, Cecilia M. Williams
Journal: Cancer Research (2010)

Abstract Mammary stem cells are suggested to be the origin of breast cancer, but are elusive and vaguely characterized. Cancer may be sustained by cancer stem cells, that are resistant to common treatments like irradiation and chemotherapy. To determine a possible association between mammary stem cells and breast cancer, we have previously made a detailed characterization of the transcriptome in murine mammary epithelial stem-like cell line (HC11) and made a thorough investigation of global gene-expression changes during stepwise differentiation using dual-color comparative microarray technique. Subsequently, we performed a cross-species comparison to reveal conserved gene expression between stem cells and subtype-specific and prognosis gene signatures. Our analysis provided a unique map of the transcriptomic changes and a number of novel mammary stem cell markers. Our comparisons showed a relationship between breast cancers of poor prognosis and stem-like gene expression. In particular the specific subtypes of basal like tumors and Luminal C types, which both have a poor prognosis, showed stem cell like gene expression pattern. We are subsequently investigating regulations of miRNAs during differentiation. We have found very strong miRNA regulation during differentation of the stem cell like cells, and are investigating the functions of key regulated miRNAs. We imply the same miRNAs could be affecting poor prognosis breast cancers. By defining the association between mammary stem cell like cells and stem cell like tumors, we can start to understand the pathways that will need to be targeted for successful treatment of poor prognosis breast cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2076.
Number of patients eligible for fast track access to drugs through the cancer drugs fund is slashed
Authors: I. Torjesen
Journal: BMJ (2013)

<h3>Abstract</h3> The Parkinson’s disease (PD) is a heterogeneous neurodegenerative disease, of which the etiological and pathological mechanisms remain unclear to date. PD has been associated with diverse movement dysfunctions and non-motor symptoms (i.e., symptom heterogeneity) and progression patterns of these symptoms differ from patient to patient (i.e., progression heterogeneity). To address these, the present investigation aims at comprehensively considering full progression course of early PDs to identify subtypes, each of which can reflect unique PD progression pattern. We retrospectively analyzed the Parkinson’s Progression Markers Initiative (PPMI) and the Parkinson Disease Biomarkers Program (PDBP) as the development and validation cohorts, respectively. An unsupervised deep learning model was built to model progression trajectories in diverse clinical manifestations and cerebrospinal fluid (CSF) biomarkers to produce a representation vector for each patient, encoding his/her symptom progression profile. Then by performing clustering analysis on the patients’ representation vectors, we identified three subtypes with distinct PD progression patterns in the PPMI cohort: Subtype I, mild baseline severity and mild symptom progression; mild baseline severity and moderate progression; and Subtype III, rapid symptom progression. Replication in the PDBP validation cohort demonstrated reproducibility of the subtypes. After that, we explored demographic factors, CSF biomarkers, neuroimaging biomarkers in brain regional atrophy, and genetic factors of the subtypes. Last, to enhance usability of the subtypes, predictive model of subtypes that relies on data at baseline and 1-year follow-up was trained. In conclusion, the identified subtypes revealed significant symptom progression patterns of PDs. Patients with similar baseline severities can even suffer from different progression pattern, leading to distinct prognosis. Demographic factors, biomarkers, and genetic components of the subtypes suggested distinct biological mechanisms and pathways potentially leading to those progression patterns. Our findings may benefit pathophysiological study, clinical practice, and clinical trials to advance PD.
OP0130 Dickkopf-Related Protein 1 Produced by Bone Decreases Osteoarthritis through VEGF Inhibition
Authors: T. Funck-Brentano, W. Bouaziz, E. Hay, M.E. Cohen-Solal
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Osteoarthritis (OA) is characterized by cartilage and subchondral bone dammage. The Wnt family is involved in joint homeostasis. We have shown that the Wnt/β-catenin pathway is activated in bone during OA, but the effect of Wnt inhibition in the subchondral bone on cartilage remodeling is unknown. <h3>Objectives</h3> We here investigated how the bone-specific inhibition of Wnt impacts the development of OA. <h3>Methods</h3> Joint destabilization by partial meniscectomy (MNX) was performed in mice overexpressing Dkk1 in bone (2.3 Col1-Dkk1Tg). Bone and cartilage lesions were assessed by microCT and histology. The effects of Dkk-1 in chondrocyte and osteoblast metabolism were further assessed using supernatant transfer and MMP expression. <h3>Results</h3> At baseline, Dkk1-Tg mice had lower bone volume which was further reduced in MNX knees. This was accompanied by a reduction of the subchondral bone and osteophyte volume. At 6 weeks after MNX, Dkk1-Tg experienced a lower OA score than WT mice (5.1±0.63 vs 8.4±0.6, p=0.002). The number of Dkk1(+) chondrocytes was high at baseline (84.2±3.1%), decreased markedly during the course of OA from week 4 (14.4±3.8%) to week 6 (5.7±1.6%), whatever the genotype. However, direct effect of Dkk1 on chondrocytes or cartilage explants induced the expression of agreccanases and metallproteinases and proteoglycans loss. When supernatants of osteoblasts previously cultured with Dkk1 were transferred on chondrocytes, this procatabolic effect was reversed, indicating and indirect underlying mechanism via osteoblasts. Because Dkk1-Tg osteoblasts produced low VEGF, we tested whether VEGF could mediate the anti-catabolic effect observed in vivo. Blocking VEGF in the supernatant of osteoblast cultures reversed the expression of MMPs by chondrocytes, and VEGF expression was decreased in vivo in the MNX knees of Dkk1-Tg mice. <h3>Conclusions</h3> Inhibition of the Wnt pathway in bone cells decreased OA severity by reducing VEGF production in the subchondral bone. Targeting bone could be a useful approach for the treatment of OA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5612
166 HCV DIVERSITY AND FIBROSIS PROGRESSION: NS5A AND CORE VARIANTS CORRELATE WITH SEVERITY OF HCV RECURRENCE AFTER LIVER TRANSPLANTATION
Authors: I. Lenci, S. Cucchiarelli, V.C. Di Maio, V. Cento, F. De Luca, M. Milana, F.P. Antonucci, D. Di Paolo, E. Giardina, G. Tisone, M. Angelico, C.F. Perno, F. Ceccherini-Silberstein
Journal: Journal of Hepatology (2013)
Tc-99m HIDA Scintigraphic Localization of Biliary Leak After Hydatid Cyst Resection
Authors: GEOFFREY R. STOREY, HUGH CARMALT, HANS Van Der WALL, KEVIN C. ALLMAN
Journal: Clinical Nuclear Medicine (1997)

A 62-year-old man had a 2-month history of abdominal distension and right upper quadrant pain. Abdominal CT scan revealed two large intrahepatic cysts and serologic testing for Echinococcus granulosis yielded positive results. Hydatid disease with liver involvement was diagnosed. The patient subsequently underwent laparotomy for deroofing/drainage of the two hydatid cysts and cholecystectomy. A CT scan performed 5 days postoperatively revealed a large perihepatic fluid collection, which proved to be bile-stained on percutaneous drainage. A large volume of bile continued to drain percutaneously. Tc-99m HIDA scintigraphy performed to identify the source of the leak showed the site of bile leakage to lie within the lateral hepatic cystic cavity. Physiologic drainage of bile into the duodenum was also demonstrated, confirming patency of the extrahepatic biliary system.
P135 Maximum inspiratory flow measured directly with an inspiratory flow metre compared with measurements from flow volume loop traces
Authors: M. C. P. Apps, M. Skipper, J. Skipper, S. Basford, V. Bryant, J. Saines, T. Andrews
Journal: Thorax (2011)

<h3>Introduction</h3> Low Maximum Inspiratory Flow is characteristic of patients with muscle weakness, Laryngeal dysfunction, or Extra-thoracic airway obstruction. We have been exploring the use of an Inspiratory Flow Metre (In Check Dial- Clement Clarke International) to help in the identification of those patients who need more detailed investigation. <h3>Methods</h3> We have compared the Inspiratory Flow rate (I) with the flow metre against Maximum Inspiratory flows taken from a flow volume loop (FVI) taken as part of routine lung function testing in 100 sequential subjects attending the Cardio Respiratory department for lung function testing. <h3>Results</h3> We have found major variability in the FVI on flow volume traces despite attempts to obtain traces with maximum volume and effort. Only 36% of subjects had variability between attempts of &lt;1 l/s, with 64% showing variability between attempts of &gt;1 l/s, 24% of &gt;2 l/s, and 3% &gt;3 l/s. For measurements using the Inspiratory Flow metre If I&gt;2 l/s all of the 38% of subjects showed FVI of 2 l/s or more. With I of &lt;2 l/s there was agreement between the two methods ±0.3 l/s in 26%, and a further 14% with FVI of &lt;2 l/s. 40% of subjects with Inspiratory Flow (I) of &lt;2 l/s had FVI of &lt;2 l/s. But in 22% of subjects I &lt;2 l/s but FVI &gt;2 l/s. FVI-I showed mean difference for these subjects of 2.4 l/s (range 0.9–4 l/s). In total 78% of subjects showed concordance of Maximum Inspiratory Flow to &gt;2 l/s or &gt;2 l/s between the two measurements and for 22% the inspiratory flow metre reading of &lt;2 l/s did not reflect maximum Inspiratory Flow. <h3>Conclusion</h3> There are major variations in the Maximum Inspiratory Flow measured with a flow volume loop but for a simpler measurement with an Inspiratory Flow metre if Maximum flow is &gt;2 l/min then it is unlikely that Inspiratory flow is compromised. A simple clinic based measurement can be useful to exclude limitation of Inspiratory Flow but if abnormal further investigation is needed.
Case 28-1992
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, M.L. Gruber, R.A. Sobel
Journal: New England Journal of Medicine (1992)

Presentation of Case First admission. A 45-year-old man was admitted to the hospital because of increasing confusion and a lymphocytic pleocytosis.The patient was well until approximately 3 1/2 months earlier, in late February, when he traveled to Texas on a business trip. During his stay he worked in an enclosure where numerous insects were present and was exposed to fumigation in a motel room; there was no available information about the agent used. At some point he began to experience a metallic taste accompanied by anorexia. On returning to his home in the metropolitan Boston area two weeks . . .
Correspondence
Authors: Aman U. Buzdar, H.A. Chaudri, Patrick F. Trunet
Journal: Journal of Clinical Oncology (2000)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.8.1802 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10764444 Correspondence Aman U. Buzdar x Aman U. Buzdar Search for articles by this author H.A. Chaudri x H.A. Chaudri Search for articles by this author , Patrick F. Trunet x Patrick F. Trunet Search for articles by this author Show More University of Texas M.D. Anderson Cancer Center HoustonTXNovartis Pharma AGBaselSwitzerlandNovartis Pharma SARueil-MalmaisonFrance https://doi.org/10.1200/JCO.2000.18.8.1802 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology jco J Clin Oncol Journal of Clinical Oncology JCO 0732-183X 1527-7755 American Society of Clinical Oncology Response 01 04 2000 In Reply: Our letter 1 on the long duration of response with letrozole 2.5 mg supplemented the original article published in the Journal of Clinical Oncology. 2 The letter summarized the results of the updated analysis, which have been presented by participating investigators at several local and international meetings. 3,4 The manuscript for the North American study to which Dr Buzdar refers is in preparation. Based on discussions in early 1999 with the manuscript committee of which Dr Buzdar is the chair, the committee recommended that the publication should include more mature survival data. These results became available in December 1999. The trialists are eagerly anticipating the peer review of the full report. We intend to submit the manuscript to the Journal of Clinical Oncology in the near future. 7. Chaudri HA, Trunet PF: Letrozole: Updated duration of response. J Clin Oncol 17::3859,1999-3860, Google Scholar7. Dombernowsky P, Smith I, Falkson G, et al: Letrozole, a new oral aromatase inhibitor for advanced breast cancer: Double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate. J Clin Oncol 16::453,1998-461, Link, Google Scholar7. Gershanovich M, Chaudri HA, Hornberger U, et al: Comparison of letrozole 2.5 mg (Femara®) with megestrol acetate (MA) and with aminoglutethimide (AG) in patients with visceral disease. Poster presented at 20th San Antonio Breast Cancer Symp, San Antonio, TX, December 1997 Google Scholar7. Gardin G, Fornasiero A, Romieu G, et al: Long duration of response with letrozole 2.5 mg (Femara®) in two trials in postmenopausal women with advanced breast cancer after anti-estrogen therapy. Poster presented at 1st Eur Breast Cancer Conf (EBCC), Florence, September 1998. Eur J Cancer 34:1998 (suppl 5) (abstr 46) Google Scholar