tbuckley/cabot-search huggingface dataset:
PB2240 EPIDEMIOLOGICAL DATA ON MYELOFIBROSIS IN ALBANIAN POPULATION (1999‐2018)
Authors: E. Çalliku, A. Perolla, P. Pulluqi, T. Caja, A. Cili, A. Ivanaj
Journal: HemaSphere (2019)

Background: Worldwide published epidemiological data on primary and secondary myelofibrosis (MF) are scarce, and multiple sources are needed to assess the disease burden in each country, in our country we have a lack of epidemiological data on MPD and MF. Aims: The aim of our study is to evaluate the annual incidence of Myelofibrosis in the Albanian population during the period of time from 1999‐2018. Methods: In our study the data were collected from the registries in our Service of Hematology and from the registries in the Department of Statistics, UHC “Mother Teresa” and were analyzed with SPSS 22.0. We have analyzed the data of all patients, age &gt; 18 years, diagnosed with Myelofibrosis and hospitalized in the UHC “Mother Teresa” and in our Service of Hematology from 1999 to 2018. Results: During the interval 1999‐2018 in our hospital are diagnosed 108[100%] patients with MF, 54 pts (50%) males, and 54 pts (50%) female. The annual incidence of MF in Albania results around 0,22 new cases / 100,000 habitants per year. The median incidence of MF is about 5,7 new cases per year with a peak in 2013 (13 new cases) and an increase with respectively 10 new cases in 2017 and 15 new cases in 2018. The median age at the moment of the diagnosis resulted in 62,5 years old (interval range 25‐83 years old) Almost all the patients were on advanced stages of MF at the moment of the diagnosis (95%). Actually, 49 patients are on treatment with Ruxolitinib since 2015. Summary/Conclusion: A careful study, using standardized definitions of MF and complete assessment of patients including both primary and secondary MFs, should be performed to estimate the population aimed to receive novel era treatments for these neoplasms
EULAR points to consider for the use of big data in rheumatic and musculoskeletal diseases
Authors: Laure Gossec, Joanna Kedra, Hervé Servy, Aridaman Pandit, Simon Stones, Francis Berenbaum, Axel Finckh, Xenofon Baraliakos, Tanja A Stamm, David Gomez-Cabrero, Christian Pristipino, Remy Choquet, Gerd R Burmester, Timothy R D J Radstake
Journal: Annals of the Rheumatic Diseases (2019)

Background Tremendous opportunities for health research have been unlocked by the recent expansion of big data and artificial intelligence. However, this is an emergent area where recommendations for optimal use and implementation are needed. The objective of these European League Against Rheumatism (EULAR) points to consider is to guide the collection, analysis and use of big data in rheumatic and musculoskeletal disorders (RMDs). Methods A multidisciplinary task force of 14 international experts was assembled with expertise from a range of disciplines including computer science and artificial intelligence. Based on a literature review of the current status of big data in RMDs and in other fields of medicine, points to consider were formulated. Levels of evidence and strengths of recommendations were allocated and mean levels of agreement of the task force members were calculated. Results Three overarching principles and 10 points to consider were formulated. The overarching principles address ethical and general principles for dealing with big data in RMDs. The points to consider cover aspects of data sources and data collection, privacy by design, data platforms, data sharing and data analyses, in particular through artificial intelligence and machine learning. Furthermore, the points to consider state that big data is a moving field in need of adequate reporting of methods and benchmarking, careful data interpretation and implementation in clinical practice. Conclusion These EULAR points to consider discuss essential issues and provide a framework for the use of big data in RMDs.
OP0048 GENOME-WIDE META-ANALYSIS REVEALED MULTIPLE NOVEL LOCI ASSOCIATED WITH SERUM URIC ACIDLEVELS IN JAPANESE
Authors: Hirotaka Matsuo, Masahiro Nakatochi, Masahiro Kanai, Akiyoshi Nakayama, Asahi Hishida, Yusuke Kawamura, Mayuko Nakajima, Yoichiro Kamatani, Nariyoshi Shinomiya, Mitsuhiro Yokota, Kenji Wakai, Yukinori Okada
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Uric acid is an end metabolite of purines which is produced predominantly in the liver and is excreted by the kidneys and the intestine. Genes for urate transporters and proteins associated with cell metabolism might therefore be expected to be associated with serum uric acid (SUA). Indeed, urate transporter genes such as SLC22A12 (also known as URAT1), SLC2A9 (GLUT9), and ABCG2 (BCRP) have been markedly associated with SUA<sup>1,2</sup>, hyperuricemia, and gout<sup>3-5</sup>. To date, several genome-wide association studies (GWASs) of SUA have been performed with some populations including Japanese. <h3>Objectives</h3> We have investigated the genetic loci that influence SUA with more than 120,000 Japanese individuals with a genome-wide meta-analysis and have compared our findings with those of previous GWASs. <h3>Methods</h3> We performed a genome-wide meta-analysis based on three Japanese cohorts including those of the Japan Multi-institutional Collaborative Cohort (J-MICC) Study, the Kita-Nagoya Genomic Epidemiology (KING) Study, and the BioBank Japan (BBJ). We also performed the trans-ethnic meta-analysis across the present study and the Global Urate Genetics Consortium (GUGC)-based study to carry out fine-mapping analysis. <h3>Results</h3> We identified 8,948 variants at 36 genomic loci (P&lt;5×10<sup>–8</sup>) including eight novel loci (Figure 1). Of these, missense variants of <i>SESN2</i> and <i>PNPLA3</i> were predicted to be damaging to the function of these proteins; another five loci—<i>TMEM18</i>, <i>TM4SF4</i>, <i>MXD3-LMAN2</i>, <i>PSORS1C1-PSORS1C2</i>, <i>HNF4A</i>—are related to cell metabolism, proliferation, or oxidative stress; and the remaining locus, <i>LINC01578</i>, is unknown. We also identified 132 correlated genes whose expression levels are associated with SUA-increasing alleles. These genes are enriched for the UniProt transport term, suggesting the importance of transport-related genes in SUA regulation. Furthermore, trans-ethnic meta-analysis across our own meta-analysis and the GUGC has revealed 15 more novel loci associated with SUA (Figure 2). <h3>Conclusion</h3> Our findings thus provide important insight into SUA regulation and the pathogenesis of hyperuricemia and gout, and they provide a potential basis for the development of new treatments for these diseases. <h3>References</h3> [1] Köttgen, A. et al. Nat Genet45, 145-54 (2013). [2] Kanai, M. et al. Nat Genet50, 390-400 (2018). [3] Matsuo, H. et al. Sci Transl Med1, 5ra11 (2009). [4] Woodward, O.M. et al. Proc Natl Acad Sci U S A106, 10338-42 (2009). [5] Nakayama, A. et al. Ann Rheum Dis76, 869-877 (2017). <h3>Disclosure of Interests</h3> None declared
Провідні фактори впливу на якість медичної допомоги пацієнтам із біліарною патологією на вторинному рівні
Authors: Yu.M. Stepanov, І.Yu. Skirda
Journal: GASTROENTEROLOGY (2014)

Нашою метою було визначити фактори, що впливають на клінічні результати стаціонарної допомоги при захворюваннях біліарної системи. У дослідженні доведено залежність між потужністю лікарні та клінічними результатами ендоскопічного дренажу при гострому холангіті. Встановлено, що термін перебування таких пацієнтів у лікарнях з високою потужністю був коротшим ((26,8 ± 22,6) дня у лікарнях низької потужності проти (23,3 ± 21,5) дня в лікарнях середньої та (19,7 ± 17,2) дня у лікарнях високої потужності, р &lt; 0,001). Також рідше реєструвались дренажні ускладнення (5,6 % у лікарнях низької потужності проти 4,3 % у лікарнях середньої та 3,2 % у лікарнях високої потужності, р &lt; 0,001). Виявлено, що ендоскопічний жовчний дренаж, ендоскопічна ретроградна холангіопанкреатографія та назобіліарний жовчний дренаж є корисними при жовчній декомпресії. Досвід ендоскопістів у ефективному виконанні ендоскопічного жовчного дренажу, а також достатнє ресурсне забезпечення у лікарнях високої потужності пов’язані з кращими клінічними результатами ендоскопічних втручань при гострому холангіті. У пацієнтів похилого віку та з тяжкими супутніми захворюваннями підвищувався ризик ускладнень внаслідок таких втручань. Ендоскопічні втручання потребують висококваліфікованої команди, яка складається з ендоскопістів та інших фахівців, у тому числі з реабілітації. Такі фахівці, як правило, працюють у лікарнях з високою потужністю і можуть забезпечити міждисциплінарну медичну допомогу, що значною мірою сприяє покращенню клінічних результатів.
Abstract 19352: Utilizing the Genome Aggregation Database, in silico Tools, and Patch Clamp Heterologous Expression Studies to Demote Previously Published Type 1 Long QT Syndrome Mutations From Pathogenic to Benign
Authors: Daniel J Clemens, Anne R Lentino, Jamie D Kapplinger, Dan Ye, Wei Zhou, David J Tester, Michael J Ackerman
Journal: Circulation (2017)

Introduction: Loss of function mutations in the KCNQ1-encoded Kv7.1 potassium channel cause type 1 long QT syndrome (LQT1). To date, hundreds of unique KCNQ1 missense variants (MSVs) have been publ...
Identifying Lineage-Specific Targets of Natural Selection by a Bayesian Analysis of Genomic Polymorphisms and Divergence from Multiple Species
Authors: Shilei Zhao, Tao Zhang, Qi Liu, Hao Wu, Bing Su, Peng Shi, Hua Chen
Journal: Molecular Biology and Evolution (2019)

We present a method that jointly analyzes the polymorphism and divergence sites in genomic sequences of multiple species to identify the genes under natural selection and pinpoint the occurrence time of selection to a specific lineage of the species phylogeny. This method integrates population genetics models using a Bayesian Poisson random field framework and combines information over all gene loci to boost the power for detecting selection. The method provides posterior distributions of the fitness effects of each gene along with parameters associated with the evolutionary history, including the species divergence time and effective population size of external species. The results of simulations demonstrate that our method achieves a high power to identify genes under positive selection for a wide range of selection intensity and provides reasonably accurate estimates of the population genetic parameters. The proposed method is applied to genomic sequences of humans, chimpanzees, gorillas, and orangutans and identifies a list of lineage-specific targets of positive selection. The positively selected genes in the human lineage are enriched in pathways of gene expression regulation, immune system and metabolism, etc. Our analysis provides insights into natural evolution in the coding regions of humans and great apes and thus serves as a basis for further molecular and functional studies.
Segregational Drift and the Interplay between Plasmid Copy Number and Evolvability
Authors: Judith Ilhan, Anne Kupczok, Christian Woehle, Tanita Wein, Nils F Hülter, Philip Rosenstiel, Giddy Landan, Itzhak Mizrahi, Tal Dagan
Journal: Molecular Biology and Evolution (2018)

The ubiquity of plasmids in all prokaryotic phyla and habitats and their ability to transfer between cells marks them as prominent constituents of prokaryotic genomes. Many plasmids are found in their host cell in multiple copies. This leads to an increased mutational supply of plasmid-encoded genes and genetically heterogeneous plasmid genomes. Nonetheless, the segregation of plasmid copies into daughter cells during cell division is considered to occur in the absence of selection on the plasmid alleles. We investigate the implications of random genetic drift of multicopy plasmids during cell division-termed here "segregational drift"-to plasmid evolution. Performing experimental evolution of low- and high-copy non-mobile plasmids in Escherichia coli, we find that the evolutionary rate of multicopy plasmids does not reflect the increased mutational supply expected according to their copy number. In addition, simulated evolution of multicopy plasmid alleles demonstrates that segregational drift leads to increased loss frequency and extended fixation time of plasmid mutations in comparison to haploid chromosomes. Furthermore, an examination of the experimentally evolved hosts reveals a significant impact of the plasmid type on the host chromosome evolution. Our study demonstrates that segregational drift of multicopy plasmids interferes with the retention and fixation of novel plasmid variants. Depending on the selection pressure on newly emerging variants, plasmid genomes may evolve slower than haploid chromosomes, regardless of their higher mutational supply. We suggest that plasmid copy number is an important determinant of plasmid evolvability due to the manifestation of segregational drift.
PF171 DIFFERENTIAL EXPRESSION PATTERNS OF SPECIFIC LONG NONCODING RNAS AND COMPETING ENDOGENOUS RNA NETWORK IN ACUTE LYMPHOCYTE LEUKEMIA
Authors: W. Wang, J. Ma, S. Gan, Z. Jiang, L. Sun, H. Sun
Journal: HemaSphere (2019)

Background: Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) play an important role in the competitive endogenous RNA (ceRNA) networks in that they regulate protein-coding gene expression by sponging microRNAs (miRNAs). However, the roles of specific lncRNA and its related competing endogenous RNAs (ceRNA) network in acute lymphocyte leukemia (ALL) are not fully understood. Aims: The aims of this study were to use RNA expression profile bioinformatics data from cases of ALL from the Cancer Genome Atlas (TCGA), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and the Gene Ontology (GO) databases to construct a ceRNA network of mRNAs, lncRNAs, and miRNAs. Methods: All patient databases were obtained from TCGA database. lncRNA and mRNA expression files included leukemia and corresponding normal samples were also downloaded from TCGA portal. An EdgeR (empirical analysis of digital gene expression data in R) package was used to identify the RNAseq data of acute lymphoblastic leukemia. Only the differential expression genes (DEGs) with adj.P.Val < 0.05 and |log2fold change (FC)| ≥ 2 were considered as significant. Based on bioinformatics generated from miRcode, starBase, and miRTarBase, we constructed an lncRNA-miRNA-mRNA network (ceRNA network) in ALL. Database for annotation, visualization and integrated discovery (DAVID), was used for GO analysis to understand the functions of targeted genes in terms of biological process (BP), cellular component (CC) and molecular function (MF). In addition, KEGG and an R Package, clusterProfiler, was distinguished pathway enrichment of each targeted gene. Cutoff value was set as P value < 0.05. Results: We found 755 differentially expressed lncRNAs and 6131 differentially expressed genes (DEGs). The functional enrichment indicated that the DEGs mainly regulated the pathways of programmed cell death, cell cycle, apoptosis and so on. Through integrated lncRNA-mRNA and miRNA-mRNA pairs, the ceRNA network was constructed. The resulting ceRNA network included 395 mRNAs, 135 lncRNAs and 31 miRNAs. 18 out of the 135 lncRNAs (RP11-497G19.2, LOC339535, LA16c-329F2.1, AK127309, XLOC_006664, RP1-16A9.1, RP11-69I8.3, LOC100507254, KB-1183D5.14, LOC100506305, RP11-87C12.5, WASIR1, RP3-523C21.1, RP11-325F22.2, AC002454.1, LOC286367, LOC286367, RP3-523C21.2) were identified and found to be associated with the complete remission rate of ALL patients (P < 0.05)Summary/Conclusion: Our results showed lncRNA expression patterns and a complex ceRNA network in ALL. Furthermore, we identified 18 lncRNAs as novel, potential prognostic biomarkers for ALL. However, futher studies on verification of ceRNA network are needed.
A Time to Die
Authors: Dean Gianakos
Journal: Annals of Internal Medicine (2019)

On Being a Doctor18 June 2019A Time to DieDean Gianakos, MDDean Gianakos, MDCentra Health, Lynchburg, Virginia (D.G.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M18-2754 Audio Reading - “A Time to Die” Audio. Virginia Hood, MD, Associate Editor, reads “A Time to Die” by Dean Gianakos, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail I've made many mistakes before, but none like this one.Maggie was in her mid-60s when I met her in 2002. She had just moved to town and needed a general internist. On that first visit, we connected right away. I'll never forget her gray curly hair and the sparkling eyes behind her big gray glasses. So warm and so engaging! We talked about almost everything: God, family, and children. Her beloved husband, Harry. Her career as an executive in a South Carolina accounting firm.“I don't know if I was the first woman they ever hired, Dr. G. I ... Author, Article, and Disclosure InformationAffiliations: Centra Health, Lynchburg, Virginia (D.G.)Corresponding Author: Dean Gianakos, MD, Centra Health, 1901 Thomson Drive, Lynchburg, VA 24501; e-mail, dean.[email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “A Time to Die” Audio. Virginia Hood, MD, Associate Editor, reads “A Time to Die” by Dean Gianakos, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 18 June 2019Volume 170, Issue 12Page: 899KeywordsAnxietyDyspneaInterstitial lung diseasesMorphineMusclesOxygenPulmonary functionThoraxTwinsWalking ePublished: 18 June 2019 Issue Published: 18 June 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract O.56: Myocardial Fibrosis in Patients with a History of Kawasaki Disease: a Pilot Study
Authors: Susan M Dusenbery, Jane W Newburger, Kimberlee Gauvreau, Annette Baker, Andrew J Powell
Journal: Circulation (2015)

Background: Myocarditis occurs in acute Kawasaki disease (KD), and case series with endomyocardial biopsy report that KD patients (pts) may have myocardial fibrosis. The new cardiac magnetic resonance (CMR) technique of myocardial T1 measurement is a noninvasive means of measuring diffuse myocardial fibrosis. We sought to assess the prevalence and risk factors for diffuse myocardial fibrosis in KD pts using CMR. Methods: In this retrospective study, all pts with KD who had a CMR with extracellular volume fraction (ECV) measurement at Boston Children’s Hospital were included. The ECV, a measure of diffuse fibrosis, was calculated in the mid-left ventricle by measuring T1 values for blood pool and myocardium before and after gadolinium with a Look-Locker technique, and adjusting for hematocrit. Myocardium with focal fibrosis as evidenced by late gadolinium enhancement (LGE) was excluded. ECV results were compared to values from control subjects (n=20; median age 16 yrs (range, 11-36)) who had a normal CMR exam, and no history of left heart disease or cardiomyopathy. Results: Subjects (n=10) had a median age at CMR of 13 yrs (range, 8-36), median age at KD diagnosis of 3 yrs (0.3-11), and median time interval from diagnosis to CMR of 10 yrs (0.3-34). Nine pts had coronary aneurysms and the other 1 had mild left ventricular dysfunction. All 3 pts with a known history of myocardial infarction (MI) had a LGE pattern consistent with MI. LGE with a MI pattern was also seen in 1 additional pt without a history of MI but who had undergone coronary bypass surgery. Overall, ECV was not significantly different in KD pts and controls (0.25 ± 0.03 (range, 0.21-0.30) vs. 0.24 ± 0.03 (range, 0.18-0.28), p=0.29). One pt (10%) had an increased mean ECV (&gt;0.28). ECV was not associated with indexed LV mass, mass/volume ratio, ejection fraction, or LGE. Conclusions: In this small pilot study of KD pts most of whom had aneurysms, diffuse myocardial fibrosis based on ECV did not differ significantly from that in normal control subjects, although 1 in 10 pts had an ECV above the normal range. Future larger studies should compare ECV in KD pts with and without aneurysms to define the risk of myocardial fibrosis after KD and to guide future recommendations for follow-up and therapy.
SP0133 HOW TO ASSESS US LESIONS FOR GOUT + DEMO
Authors: Sara Nysom
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Gout is the most common inflammatory joint disease in Western developed countries. Diagnosis and monitoring have historically been based upon clinical assessment combined with biochemical results (primarily p-urate) but over the last decade ultrasonography (US) has received increasing attention for these purposes. US has been shown able to detect monosodium urate deposits in both joints and tendons. In 2015 the Outcome Measures in Rheumatology (OMERACT) US Working Group developed definitions of structural lesions in gout. These include double contour sign (deposits of crystals on the surface of cartilage), tophus (larger hyper-echoic aggregation of crystals), aggregates (small hyper-echoic deposits) and erosion (1). The double contour sign has been included in the ACR/EULAR 2015 gout classification criteria as a way to visualize urate deposits in joints (2). Furthermore, US can visualize potential concomitant inflammatory aspects of gout since it can visualize both joint inflammation and tenosynovitis. In this talk the diagnostic properties of US will be described and the potential risk of false positive results due to artefacts or misinterpreted lesions will be discussed. Furthermore, the potential role of US in monitoring of treatment response will be explored. <h3>References:</h3> [1] Gutierrez M, Schmidt WA, Thiele RG, Keen HI, Kaeley GS, Naredo E, Iagnocco A, Bruyn GA, Balint PV, Filippucci E, Mandl P, Kane D, Pineda C, Delle Sedie A, Hammer HB, Christensen R, D"Agostino MA, Terslev L; OMERACT Ultrasound Gout Task Force group. International Consensus for ultrasound lesions in gout: results of Delphi process and web-reliability exercise. Rheumatology (Oxford). 2015;54(10):1797-805. [2] Neogi T, Jansen TLTA, Dalbeth N, Fransen J, Schumacher HR, et al. 2015 Gout Classification criteria: an American College of Rheumatology/European Leaque Against Rheumatisme collaborative initiative. Ann Rheum Diss 2015; 74: 1789-1798. <h3>Disclosure of Interests:</h3> None declared