tbuckley/cabot-search huggingface dataset:
THU0626 SOCIAL NETWORKS AS A SOURCE OF INFORMATION FOR PATIENTS WITH RHEUMATIC DISEASES
Authors: Daniel G. Fernández-Ávila, Julián Barahona-Correa, Diana Romero-Alvernia, Angel García, Oscar Muñoz
Journal: Annals of the Rheumatic Diseases (2019)

relevant information.There is also functionality for the rheumatology team to reply to the referral with advice, which creates a new permanent document in the patient's EPR.The Orthopaedic team, who are the first point of call for hot joints in our Trust, were consulted to ensure that there were not any unintended consequences as a result of this change.The form included the following sentence to avoid delays in patient care for septic arthritis: 'patients with suspected septic arthritis should be referred to Orthopaedics by ringing the on-call registrar'. Conclusion:The current method of paper rheumatology referrals was inefficient and referrals often lacked vital information.The new electronic system will ensure relevant items are included in the referral and that there is a clear audit trail of the referral process.Referrals will be reevaluated again in three months to assess the impact of this change on outcomes including time to rheumatology review and inpatient bed stay.In the second round of this project we plan to include an education component onto the rheumatology referral form.For example, if gout is suspected, the referrer will be linked to guidelines and patient information sheets to assist best management whilst awaiting review.We would encourage others to consider their referral systems-could you improve yours?
Evidence for a Unique DNA-Dependent RNA Polymerase in Cereal Crops
Authors: Joshua T Trujillo, Arun S Seetharam, Matthew B Hufford, Mark A Beilstein, Rebecca A Mosher
Journal: Molecular Biology and Evolution (2018)

Gene duplication is an important driver for the evolution of new genes and protein functions. Duplication of DNA-dependent RNA polymerase (Pol) II subunits within plants led to the emergence of RNA Pol IV and V complexes, each of which possess unique functions necessary for RNA-directed DNA Methylation. Comprehensive identification of Pol V subunit orthologs across the monocot radiation revealed a duplication of the largest two subunits within the grasses (Poaceae), including critical cereal crops. These paralogous Pol subunits display sequence conservation within catalytic domains, but their carboxy terminal domains differ in length and character of the Ago-binding platform, suggesting unique functional interactions. Phylogenetic analysis of the catalytic region indicates positive selection on one paralog following duplication, consistent with retention via neofunctionalization. Positive selection on residue pairs that are predicted to interact between subunits suggests that paralogous subunits have evolved specific assembly partners. Additional Pol subunits as well as Pol-interacting proteins also possess grass-specific paralogs, supporting the hypothesis that a novel Pol complex with distinct function has evolved in the grass family, Poaceae.
AB0557 NON-CORONARY CARDIAC MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS IN ADULTS
Authors: Nouha Ghriss, sameh sayhi, Najeh Boussetta, Nour El Houda Gueddich, Faida Ajili, Nadia Ben Abdelhafidh, Bassem Louzir
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Systemic lupus erythematosus (SLE) is a common chronic multi-system autoimmune disorder of unknown etiology causing injury to many organ Systems. It predominantly affects young women. Cardiac manifestations develop in the majority of patients with SLE at some time during the course of their disease. <h3>Objectives:</h3> The aim of our study is to assess cardiac abnormalities in patients with systemic lupus erythematosus (SLE) by echocardiography and to compare the 2 groups of patients with and without cardiac manifestations. <h3>Methods:</h3> We have performed a transversal, descriptive study of SLE patients hospitalized in the Internal Medicine department at the Military Hospital of Tunis between January 2016 and June 2018. Diagnosis of SLE was made according to the criteria of ACR. All patients underwent a cardiac ultrasound externally or during their stay in our department. <h3>Results:</h3> The patients were 61 females and 19 males (sex-ratio=3) with a mean age of 38 years. Fourty two patients had cardiac involvement. They were 33 female and 9 male with a mean age of the disease of 31,8 years (16-80 years) at the beginning of the disease and 41 years at the time of the study. 83% of patients were symptomatic. The symptoms were dominated by objectified chest pain (43%). In Doppler echocardiography, pericarditis was found in 23 patients (55%) with a single case of cardiac tamponade. Libman Saks endocarditis and lupus myocarditis were found in one case each. Pulmonory hypertension (HTP) was observed in 16 patients (38%) and valvular disease in 22 patients (52%). Cardiomegaly was observed in 9 patients (21%). Electrical abnormalities were dominated by microvoltage found in 8 patients. The general symptoms (83%), skin lesions (76%) and musculoskeletal involvement (64%) were the most frequent events associated with the cardiac manifestations in group 1. ANA were positive in 97% of cases and antiphospholipid antibodies in 24%. Prednisone: 1mg/kg/day and immunosuppressive therapy were indicated respectively in 71% and 38% of patients. <h3>Conclusion:</h3> Cardiac abnormalities are very common in lupus patients even when clinically asymptomatic. SLE is among systemic diseases most providers of heart disease. Echocardiography is an excellent non-invasive tool for cardiac evaluation. Their research must be systematic with echocardiography in order to reduce subsequent cardiac morbidity and mortality among the lupus patients. <h3>Disclosure of Interests:</h3> None declared
PB2193 GENE EXPRESSION PROFILE IN PRIMARY MYELOFIBROSIS: ROLE OF ASXL1
Authors: S. Sánchez Sosa, C. Bilbao Sieyro, Y. Florido Ortega, E. González Pérez, M. D. L. N. Saez Perdomo, R. Stuckey, G. Santana Santana, M. T. Molero Labarta, J. F. Loro Ferrer, M. T. Gómez Casares
Journal: HemaSphere (2019)

Background: Primary myelofibrosis (PMF) is a BCR‐ABL1 ‐negative myeloproliferative neoplasm characterized by aberrant differentiation of all myeloid lineages and profound disruption of the bone marrow niche. The presence of JAK2, CALR or MPL [R1] mutation supports the diagnosis. In approximately 10% of cases classified as PMF, the genetic cause remains unknown and they are known as triple negative. Recent prognostic scores like GIPSS or MIPSS recommend the analysis of other mutations in non‐driver genes, such as ASXL1, SRSF2, EZH2, IDH1/2 and U2AF1 Q157, since they influence the risk stratification. Aims: To analyze the mRNA expression profiles of EZH2, ASXL1, RB1 and TET2 genes in a series of PMF patients with known mutational status of JAK2 V617F, CALR and MPL Methods Our series consisted of 21 PMF patients, 6 females and 15 males, with a mean age of 70 years (range 41–87), diagnosed and treated between 1996 and 2018 at the Hospital Universitario de Gran Canaria Dr. Negrín, Spain. Four patients of our series were triple negative, 13 JAK2V167 mut , 3 CALR mut and 1 MPL mut . mRNA expression levels were determined by real time PCR in a LightCycler 480 Instrument II (Roche) using ABL as a control gene. Results were normalized with a cDNA pool from the peripheral blood of 10 healthy donors, which was introduced as an internal control in each experiment. SPPS V.23 software was used for statistical analyses. Results: We found that ASXL1 expression levels were significantly higher in patients with JAK2 V617F mutated compared with JAK2 V617F non‐mutated (mean 0.47 vs. 0.25, p = 0.037, Mann–Whitney U test). In the study of progression free survival, we detected a 36% decrease in the probability of progression to AML or death per unit of ASXL1 expression (p = 0.007, Cox regression test). No significant associations were found between expression levels of the other genes studied ( RB1, TET2 and EZH2 ) and triple negative status. Summary/Conclusion: ASXL1 mutations are common in myeloid diseases and, in these cases, ASXL1 mutations are associated with worse overall survival and leukemia‐free survival. While the impact of ASXL1 mutations has been well‐studied, the impact of ASXL1 expression levels on patient outcome is less studied. The positive association between higher ASXL1 expression plus JAK2 V617F mut and better progression free survival is in agreement with the fact that the opposite, that is, inactivating ASXL1 mutations plus triple negative status, contribute to poor prognosis. These preliminary results should be confirmed in further studies with a larger series.
Fasting Status of Patients Undergoing Ambulatory Laboratory Testing
Authors: Eva Tseng, Jodi B. Segal, Nisa M. Maruthur
Journal: Diabetes Care (2019)

Many studies use glucose values from electronic medical record data to identify patients with prediabetes and diabetes (1–3). Since diagnostic criteria are based on fasting glucose (4), investigators often choose to assume that patients were fasting if phlebotomy was performed in the morning. We sought to assess the validity of the assumption that outpatient morning measurements are fasting measures.

We surveyed adult patients (age ≥18 years) presenting for phlebotomy at the Johns Hopkins Outpatient Center between 7:00 a.m. and noon over 2 weeks in November 2018. Patients responded to a four-question written survey provided by the registration staff. The survey asked 1 ) about their fasting status, 2 ) whether the ordering provider instructed them to fast, 3 ) whether they were getting a glucose and/or cholesterol test (“If you know which blood test(s) you are getting done, please select ones that are included on the list below,” with answer options of “glucose” and “cholesterol panel”), and 4 ) what …
Abstract 15208: Long-Term Outcomes After Transatrial Repair of Tetralogy of Fallot: 25 Years Experience
Authors: Yves d'Udekem, John C Galati, Glenda J Rolley, Igor E Konstantinov, Robert G Weintraub, Leeanne E Grigg, James M Ramsey, Gavin R Wheaton, Sarah A Hope, Michael M Cheung, Christian P Brizard
Journal: Circulation (2012)

Objective. Transatrial repair of Tetralogy of Fallot has been adopted in Melbourne since 1980. This review examines long-term outcomes of the technique emphasizing survival and reoperation. Methods...
PB1974 PYRUVATE KINASE DEFICIENCY IN FOUR CHILDREN WITH TWO UNPUBLISHED MUTATIONS
Authors: E. Unal, V. Gok, N.B.A. Roy, R. Hipkiss, K. Howard, A. Ozcan, E. Yilmaz, M. Karakukcu, S. Henderson, T. Patıroglu
Journal: HemaSphere (2019)

Background: Pyruvate kinase is a key enzyme of anaerobic glycolysis which helps keeping the energy level of red blood cells and their viability in circulation. The genetic heterogeneity of pyruvate kinase deficiency (PKD) is high and, to this day, over 250 different mutations have been identified. Aims: We aimed to emphasize the importance of genetic testing in patients with unexplained non‐immune hemolytic anemia. Methods: Four patients who had been followed because of non‐spherocytic hemolytic anemia and in whom no causative enzyme deficiencies were identified were referred for targeted next‐generation sequencing using the Oxford Red Cell Panel, a 50‐gene panel for inherited anemias. Results: We studied four patients (2 females, and 2 males) with evidence of chronic hemolytic anemia aged between 4 years and 24 years. Three of the four patients had jaundice, pallor and hepatosplenomegaly, while one patient had growth retardation and hypotonicity. One patient had gallstones and also undergone splenectomy at the age of two. While homozygous mutation was detected in three of four patients, only one patient had a compound heterozygous mutations (c.602G &gt; A, c.1675C &gt; G). The five identified mutations are single nucleotide gene changes. Two of the five mutations (c.602G &gt; A, and c.172C &gt; T) are previously unpublished. Summary/Conclusion: The clinical presentation of PKD ranges from frequent transfusion in neonates to mild jaundice in adulthood. Total pyruvate kinase in liver and red cell (PKLR) gene sequencing is necessary for the characterization of all patients with PKD and for genetic counselling. We also report two previously unpublished mutations in PKLR.
PS1453 CURCUMIN INHIBITS PROLIFERATION AND INDUCES APOPTOSIS IN JAK2 MUTATED CELLS THROUGH THE INHIBITION OF JAK2/STAT AND MTORC1 PATHWAYS
Authors: J. Petiti, V. Rosso, M. Lo Iacono, C. Panuzzo, C. Fava, D. Cilloni
Journal: HemaSphere (2019)

Background: Myeloproliferative neoplasms are chronic myeloid cancers divided in Philadelphia positive and negative. The JAK2 V617F is the most common mutation in Philadelphia negative patients and results in a constitutive activation of the JAK/STAT pathway, conferring a proliferative advantage and apoptosis inhibition. Furthermore, recent studies identified a functional crosstalk between the JAK/STAT and mTOR pathways. Given the heterogeneous clinical needs of MPNs patients, identification of an effective therapy is often difficult. Therefore, the availability of new therapeutic approaches might be very attractive. Curcumin is the active phytochemical component of the Curcuma longa plant. Previous studies showed that curcumin can suppress JAK2/STAT signaling pathways in different type of cancer and injuries. Aims: In this study, we investigated the anti‐proliferative and pro‐apoptotic effects of curcumin in JAK2 V617F cell line and in primary cells. Methods: HEL cell line and cells from patients affected by myeloproliferative neoplasms have been incubated with increasing concentrations of curcumin for different time. Apoptosis and proliferation were evaluated. Subsequently, JAK2/STAT and AKT/mTOR pathways were investigated at both RNA and protein levels. Results: We showed that curcumin strongly inhibited the proliferation and induced apoptosis in a dose and time dependent manner in HEL cells. Furthermore, we found that curcumin markedly reduced JAK2 phosphorylation and, consequently, the activation of its downstream effectors STAT3 and STAT5 in HEL cells. We observed that JAK2/STAT inhibition induced the down regulation of Pim family members in HEL cell line and in patient specimens. Farther, our results in HEL cells showed that curcumin negatively regulated the mTORC1 complex formation. As a consequence, we observed a strong inhibition of mTORC1 downstream effectors 4eBP1 and p70s6K phosphorylation. Our preliminary data on cells from MPNs patients showed that the in vitro curcumin treatment significantly promoted apoptosis and reduced the expression of Pim family members, bringing back their mRNA expressions to comparable levels with healthy subjects ones. Furthermore, the curcumin effect was strengthened by the observation that CD177, an antigen over expressed in neutrophils of the majority of MPNs patients, was down regulated by curcumin. Summary/Conclusion: In conclusion, the present study showed that curcumin exerts an antitumor effect on human JAK2 mutated cells by inducing apoptosis and inhibition of proliferation, through the regulation of both JAK2/STAT and mTORC1 pathways. These findings suggest that curcumin seems to be a promising nutraceutical compound that should be further evaluated in different pharmaceutical formulation for the treatment of MPNs.
PF377 ACALABRUTINIB WITH OBINUTUZUMAB IN TREATMENT‐NAIVE AND RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA: 3‐YEAR FOLLOW‐UP
Authors: J.A. Woyach, K. Rogers, S. Bhat, J. Blachly, M. Jianfar, M.M. Frigault, A. Hamdy, R. Izumi, V. Munugalavadla, C. Quah, M.H. Wang, J.C. Byrd
Journal: HemaSphere (2019)

Background: Acalabrutinib is a highly selective, potent, covalent Bruton tyrosine kinase inhibitor. Aims: This Phase 1b/2 trial evaluated acalabrutinib with the CD20 antibody obinutuzumab in patients with treatment‐naive or relapsed/refractory chronic lymphocytic leukemia (CLL). Methods: Patients with treatment‐naive or relapsed/refractory (≥1 prior therapy) CLL were eligible. In 28‐day cycles, acalabrutinib was given orally at 100 mg twice daily or 200 mg once daily (n = 15; all switched to 100 mg twice daily) until progressive disease; obinutuzumab was given in standard fashion for 6 cycles starting with Cycle 2. The primary endpoints were overall response rate (ORR) and safety. Minimal residual disease (MRD) was assessed using flow cytometry (sensitivity 10 –4 ). Results: Nineteen treatment‐naive and 26 relapsed/refractory patients were treated. The median age of all patients was 61 years (range, 42 to 76). Patient characteristics, disposition, efficacy and MRD are in the Table . Common adverse events (any grade) were upper respiratory tract infection (71%), increased weight (71%), maculopapular rash (67%), cough (64%), diarrhea (62%), headache (56%), nausea (53%), arthralgia (51%), and dizziness (47%). Common Grade 3/4 adverse events were decreased neutrophil count (24%), syncope (11%), decreased platelet count, increased weight and cellulitis (9% each). There were 2 (4%) Grade 3 bleeding events (hematuria, muscle hemorrhage) and 1 (2%) Grade 3 atrial fibrillation event. Summary/Conclusion: Acalabrutinib plus obinutuzumab was well tolerated and yielded high response rates that were durable and deepened over time in treatment‐naive and relapsed/refractory patients with CLL. image
Infographic. Therapeutic exercise relieves pain and does not harm knee cartilage nor trigger inflammation
Authors: Alessio Bricca, Ewa M Roos, Carsten B Juhl, Søren T Skou, Danilo Oliveira Silva, Christian J Barton
Journal: British Journal of Sports Medicine (2019)

OA is a leading cause of disability worldwide and associated with pain, impaired mobility and quality of life.1 Physical activity, including therapeutic exercise, patient education and weight control are recommended in key OA treatment guidelines.2 Nevertheless, the belief that therapeutic exercise may harm knee joint cartilage remains common among people with knee OA, and health professionals treating the condition, creating a prevailing barrier to implementing evidence-based care.3–5 The current discord between evidence and persistent beliefs highlights the need for better education. Providing a clear and engaging summary of the evidence to communicate the positive impact of therapeutic exercise and physical activity on the knee joint is crucial to encourage greater acceptance of, and participation in exercise and physical activity to …
Ubiquitin specific peptidase 5 regulates colorectal cancer cell growth by stabilizing Tu translation elongation factor
Authors: Xin Xu, Aiwen Huang, Ximao Cui, Kunkun Han, Xiaodan Hou, Qun Wang, Long Cui, Yili Yang
Journal: Theranostics (2019)

Ubiquitin specific peptidase 5 (USP5) is a ubiquitous expressed deubiquitinating enzyme (DUB).It has been shown involved in DNA repair, apoptosis, inflammation, and tumor cell growth.However, the function and molecular mechanism of USP5 in colorectal cancer (CRC) are still unclear.In the present study, we asked how it affected the growth of colorectal cancer cells.Methods: A shRNA-based high-content screening was performed to identify DUBs affecting the growth of CRC cells.CCK-8 assay and xenografts were used to assess CRC cell growth, survival and tumorigenesis.RT-qPCR, immunoblotting and immunohistochemistry were carried out to quantitate USP5 expression in CRC tissues and cell lines.Immunoprecipitation and mass spectrometry analysis were performed to identify USP5-interacting proteins.Cycloheximide chase was performed to assess Tu translation elongation factor (TUFM) stability.Dual luciferase reporter assay was utilized for USP5 promoter analysis.Results: We found that USP5 was highly expressed in a group of primary CRC tissues, and the increased USP5 was correlated with clinical stages and shorter overall survival.While USP5 knockdown effectively inhibited CRC cell growth, overexpressed USP5 promoted the growth of CRC cells and made them more resistant to doxorubicin (DOX).TUFM was discovered as a substrate of USP5.USP5 deubiquitinated TUFM and increased its level in CRC cells.Enforced expression of TUFM was able to alleviate the growth inhibition induced by USP5 knockdown.Further analyses showed that EBF transcription factor 1 (EBF1) was a major regulator for USP5 transcription, and DOX inhibited EBF1-USP5-TUFM axis in CRC cells.Conclusions: USP5 was required for CRC cells and promoted their growth and resistance to chemotherapeutics.TUFM was a USP5 deubiquitinating substrate that mediated the cellular effects of USP5.The transcription of USP5 was regulated by EBF1.Thus, targeting EBF1-USP5-TUFM axis is a potential novel strategy for CRC treatment.
Codon Usage Bias in Animals: Disentangling the Effects of Natural Selection, Effective Population Size, and GC-Biased Gene Conversion
Authors: Nicolas Galtier, Camille Roux, Marjolaine Rousselle, Jonathan Romiguier, Emeric Figuet, Sylvain Glémin, Nicolas Bierne, Laurent Duret
Journal: Molecular Biology and Evolution (2018)

Selection on codon usage bias is well documented in a number of microorganisms. Whether codon usage is also generally shaped by natural selection in large organisms, despite their relatively small effective population size (Ne), is unclear. In animals, the population genetics of codon usage bias has only been studied in a handful of model organisms so far, and can be affected by confounding, nonadaptive processes such as GC-biased gene conversion and experimental artefacts. Using population transcriptomics data, we analyzed the relationship between codon usage, gene expression, allele frequency distribution, and recombination rate in 30 nonmodel species of animals, each from a different family, covering a wide range of effective population sizes. We disentangled the effects of translational selection and GC-biased gene conversion on codon usage by separately analyzing GC-conservative and GC-changing mutations. We report evidence for effective translational selection on codon usage in large-Ne species of animals, but not in small-Ne ones, in agreement with the nearly neutral theory of molecular evolution. C- and T-ending codons tend to be preferred over synonymous G- and A-ending ones, for reasons that remain to be determined. In contrast, we uncovered a conspicuous effect of GC-biased gene conversion, which is widespread in animals and the main force determining the fate of AT↔GC mutations. Intriguingly, the strength of its effect was uncorrelated with Ne.