tbuckley/cabot-search huggingface dataset:
Abstract B58: Detection of ESR1 gene fusions in breast cancer cell-derived exosomal RNA
Authors: Tiantong Liu, Jagmohan Hooda, Nils Ludwig, Theresa Whiteside, Jennifer M. Atkinson, Steffi Oesterreich, Adrian Lee
Journal: Clinical Cancer Research (2020)

Abstract Background: Estrogen receptor-positive (ER+) breast cancer is often intractable due to endocrine therapy resistance. Although ER basepair hotspot mutations have been well characterized in ~20-30% of endocrine-resistant disease, accumulating evidence from our group and others suggests that other genetic alterations such as ER fusions (e.g., ESR1-DAB2) could also play a role. As an important component of liquid biopsies, exosomes have recently gained much attention in the field of clinical oncology. It is well established that some species of RNA, typically microRNA and mRNA, are packaged into these small membrane-enclosed structures, which could potentially serve as a noninvasive biomarker to constantly and comprehensively monitor tumor progression and tumor cell evolution. We tested whether ESR1 fusions could be detected in exosomal RNA (exoRNA) produced by breast cancer cell lines. Methods: Multiple methods were used to characterize exosomes isolated from cell culture media: 1) Nanoparticle tracking analysis (NTA) confirmed concentration and size of exosomes, 2) immunoblotting identified protein markers that are enriched or lacking in exosomes, 3) transmission electron microscopy validated the size and shape of exosomes. During exoRNA extraction, DNA contamination was removed by DNase treatment. Fusion-specific regions in exoRNA were amplified by standard PCR. Results: We used breast cancer cell lines stably infected with cDNA encoding ESR1 fusions ESR1-DAB2 and ESR1-SOX9. NTA shows that our isolated exosomes had a size ranging from 30-150 nm, with the peak at 80 nm. Immunoblotting showed TSG101 and CD81 as positive markers of our exosomes, while Grp94 was negative. By RT-PCR, we identified a fusion-specific region amplified for both ESR1-SOX9 and ESR1-LPP from exoRNA for the fusion cell lines. Conclusions: Collectively, these data indicate that multiple ESR1 fusions are detectable in breast cancer cell line-derived exoRNA. Citation Format: Tiantong Liu, Jagmohan Hooda, Nils Ludwig, Theresa Whiteside, Jennifer M. Atkinson, Steffi Oesterreich, Adrian Lee. Detection of ESR1 gene fusions in breast cancer cell-derived exosomal RNA [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B58.
High cancer risk and increased mortality in patients with Peutz–Jeghers syndrome
Authors: Douglas L Riegert-Johnson, Wytske Westra, Maegan Roberts
Journal: Gut (2011)

We read with interest the informative, and needed, update on the Dutch Peutz–Jeghers syndrome (PJS) cohort by van Lier et al .1 Our group has translated Peutz's original paper from Dutch,2 and the findings …
Serodiagnostics for Severe Acute Respiratory Syndrome–Related Coronavirus 2
Authors: Matthew P. Cheng, Cedric P. Yansouni, Nicole E. Basta, Michaël Desjardins, Sanjat Kanjilal, Katryn Paquette, Chelsea Caya, Makeda Semret, Caroline Quach, Michael Libman, Laura Mazzola, Jilian A. Sacks, Sabine Dittrich, Jesse Papenburg
Journal: Annals of Internal Medicine (2020)

Accurate serologic tests to detect host antibodies to severe acute respiratory syndrome–related coronavirus 2 (SARS-CoV-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. Many use cases are envisaged, including complementing molecular methods for diagnosis of active disease and estimating immunity for individuals. At the population level, carefully designed seroepidemiologic studies will aid in the characterization of transmission dynamics and refinement of disease burden estimates and will provide insight into the kinetics of humoral immunity. Yet, despite an explosion in the number and availability of serologic assays to test for antibodies against SARS-CoV-2, most have undergone minimal external validation to date. This hinders assay selection and implementation, as well as interpretation of study results. In addition, critical knowledge gaps remain regarding serologic correlates of protection from infection or disease, and the degree to which these assays cross-react with antibodies against related coronaviruses. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation.
AB0293 FACTORS ASSOCIATED WITH INITIATION OF BIOLOGIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS IN MOROCCAN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: O. Hammou, F. Chennouf, H. Azzouzi, I. Linda
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rheumatoid arthritis (RA) is a progressive autoimmune disorder of joints that is associated with high health care costs, yet guidance is lacking on how early to initiate biologic disease-modifying antirheumatic drugs (DMARDs). Few studies have examined the factors associated with the transition from non biologic DMARDs to biologic DMARDs in RA patients. Objectives: to examine the association of patient’s comorbidities with initiation of biologic DMARDs (disease-modifying antirheumatic drugs) in rheumatoid arthritis (RA). Methods: cross-sectional study was designed on a cohort of RA patients. Sociodemographic, clinical data and comorbidities were collected. Logistic regression analysis was used to explore the impact of comorbidities on the initiation of bDMARD. The statistical analysis was done by SPSS. 20, p &lt;0.05 was considered significant. Results: among the 257 patients, 90.5% were females. Their mean age was 54.66 ± 11.9 years. The most frequent comorbidities in our population were: high blood pressure (22.5%), diabetes (16.6%), history of heart disease (5.1%), history of neoplasia (2.4%) and nephropathies (2%). RA patients with comorbidities were more likely to initiate bDMARD: high blood pressure (p = 0.003 OR=2.36, 95% CI: 1.332- 4.181), history of heart disease (p = 0.036 OR=3.01, 95% IC: 1.073-8.468) and history of neoplasia (p = 0.026 OR= 5.07, 95% CI: 1.219- 21.110). In multiple regression models, high blood pressure was associated to the initiation of biologic agents (p= 0.026, OR= 2.07, 95% CI: 1.090-3.932). Conclusion: the probability of initiating therapy with biologic agents in patients with RA is affected by different co-morbidities in our context specifically hypertension. References: [1]Machado-Alba JE, et al. Time to and factors associated with initiation of biological therapy in patients with rheumatoid arthritis in Colombia. Rev Colomb Reumatol. 2018 [2]Priyanka Gaitonde et al. Factors associated with use of disease modifying agents for rheumatoid arthritis in the National Hospital and Ambulatory Medical Care Survey. Seminars in Arthritis and Rheumatism. 2017 Disclosure of Interests: None declared
Covid-19: Lack of test and trace data is frustrating government scrutiny
Authors: Shaun Griffin
Journal: BMJ (2020)

Former health secretary Jeremy Hunt has responded with incredulity at the lack of data about the government’s test and trace programme, after the head of the service was unable to provide figures on how many tests had been completed within the first 24 hours.

The UK stopped community testing and contact tracing for covid-19 in early March, partly because of a lack of capacity.1 But after pressure from public health experts a new programme was launched on 28 May2 to great fanfare from Prime Minister Boris Johnson who said it would be “world beating.”

At an evidence hearing of the House of Commons Health and Social Care Committee on 3 June, Hunt said that Dido Harding, chair of NHS Test and Trace, had been given advance notice of four questions, including one requesting data on the proportion of tests completed in 24 hours.

Giving evidence, Harding said, “This is …
Reply to Benjamin S. Simpson, Lina M. Carmona Echeverria, Joseph M. Norris, Hashim U. Ahmed, Caroline M. Moore, and Hayley C. Whitaker's Letter to the Editor re: Gregory T. Chesnut, Emily A. Vertosick, Nicole Benfante, et al. Role of Changes in Magnetic Resonance Imaging or Clinical Stage in Evaluation of Disease Progression for Men with Prostate Cancer on Active Surveillance. Eur Urol 2020;77:501–7
Authors: Gregory T. Chesnut, Andrew J. Vickers, Behfar Ehdaie
Journal: European Urology (2020)
SAT0214 ULTRASONOGRAPHIC CHANGES OF SALIVARY GLANDS IN PRIMARY SJOGREN’S SYNDROME: A LONGITUDINAL PROSPECTIVE STUDY
Authors: H. R. Kim, K. A. Lee, S. H. Lee, S. H. Kim
Journal: Annals of the Rheumatic Diseases (2020)

Background: In the diagnosis of primary Sjogren’ syndrome (SS), salivary gland ultrasound is useful tool. Until now, there is no data for ultasonographic changes of major salivary glands over time. Objectives: This study aimed to evaluate the changes in abnormalities of salivary gland ultrasound (SGUS) over time in patients with pSS. Methods: Patients with pSS (n=70) and idiopathic sicca syndrome (n=18) underwent SGUS twice at baseline and 2 years later. The semi-quantitative SGUS score (0-48) was used, which comprises five parameters: parenchymal echogenicity, homogeneity, hypoechoic areas, hyperechogenic reflections, and clearness of posterior borders. The intraglandular power Doppler signal (PDS) was also assessed. The changes of these SGUS variables were compared in patients with pSS and idiopathic sicca syndrome. Results: The median (interquartile range) total SGUS scores at baseline was 27 (14) in patients with and 4 (3) in those with idiopathic sicca syndrome ( p &lt;0.001). In the pSS group, the total SGUS scores and the SGUS scores for bilateral parotid glands were significantly increased during median 23.4 month follow-up ( p =0.013 and p =0.011, respectively). Homogeneity and hypoechoic areas were the domain to show statistically significant progression of SGUS scores. None of the SGUS scores changed significantly in the patients with idiopathic sicca syndrome. In patients with pSS, baseline and follow-up PDS sum scores of four salivary glands were significant higher in worsening SGUS group (n=13) than no change/improvement SGUS group (n=55/2). Conclusion: The structural abnormalities in major salivary glands assessed using SGUS scores progressed significantly in patients with pSS. In pSS group, 18.6% patients had worsening SGUS scores during 2 years. Intra-glandular hypervascularity was associated with worsening of salivary gland abnormalities. References: [1]Delli K, Dijkstra PU, Stel AJ, Bootsma H, Vissink A, Spijkervet FK. Diagnostic properties of ultrasound of major salivary glands in Sjogren’s syndrome: a meta-analysis. Oral diseases. 2015;21(6):792-800. [2]Jousse-Joulin S, Devauchelle-Pensec V, Cornec D, Marhadour T, Bressollette L, Gestin S, et al. Brief Report: Ultrasonographic Assessment of Salivary Gland Response to Rituximab in Primary Sjogren’s Syndrome. Arthritis &amp; rheumatology (Hoboken, NJ). 2015;67(6):1623-8. [3]Gazeau P, Cornec D, Jousse-Joulin S, Guellec D, Saraux A, Devauchelle-Pensec V. Time-course of ultrasound abnormalities of major salivary glands in suspected Sjogren’s syndrome. Joint, bone, spine: revue du rhumatisme. 2018;85(2):227-32. [4]Lee KA, Lee SH, Kim HR. Diagnostic and predictive evaluation using salivary gland ultrasonography in primary Sjogren’s syndrome. Clinical and experimental rheumatology. 2018;36 Suppl 112(3):165-72. Acknowledgments: : This work was funded by the Konkuk University Medical Center Research Grant 2019. Disclosure of Interests: None declared
Abstract 12570: Patient Perspectives on Cholesterol Lowering Therapies Among Those Who Report Statin-associated Adverse Events. Results From a National Survey in the Getting to an Improved Understanding of Low-density Lipoprotein Cholesterol and Dyslipidemia Management (GOULD) Registry
Authors: Robert S Rosenson, Katie Mues, Yuyin Liu, Christie M Ballantyne, James A De Lemos, Shushama Alam, Mary Elliott-Davey, Deepak L Bhatt, Mikhail N Kosiborod, Christopher P Cannon
Journal: Circulation (2019)

Introduction: Patient experiences while taking a statin, including adverse events, influences treatment adherence, future risk of cardiovascular disease (CVD) events and healthcare expenditures. Un...
Global outbreak research: harmony not hegemony
Authors: Tamuna Akhvlediani, Syed M Ali, Derek C Angus, Yaseen M Arabi, Sheharyar Ashraf, J Kenneth Baillie, Barnabas Bakamutumaho, Abi Beane, Fernando Bozza, Stephen J Brett, Roberto Bruzzone, Gail Carson, Lyndsey Castle, Michael Christian, J Perren Cobb, Matthew J Cummings, Eric D'Ortenzio, Menno D de Jong, Emmanuelle Denis, LPG Derde, Emily Dobell, Arjen M Dondorp, Jake W Dunning, Dean Everett, Jeremy Farrar, Rob Fowler, Dilanthi Gamage, Zhancheng Gao, Charles D Gomersall, Anthony C Gordon, Rashan Haniffa, Hayley Hardwick, Madiha Hashmi, Mohammad Hayat, Frederick G Hayden, Antonia Ho, Peter Horby, Peter W Horby, Nina Jamieson, Issrah Jawad, Marshall John, Kalynn Kennon, Saleh Khaskheli, Saye H Khoo, Trudie Lang, James Lee, Lowell Ling, John C Marshall, Mohammad I Memon, France Mentré, Laura Merson, Sarah Moore, Srinivas Murthy, Alistair Nichol, Max R O'Donnell, Piero L Olliaro, Piero Olliaro, Peter J Openshaw, Rachael Parke, Rui Pereira, Daniel Plotkin, Mark Pritchard, Ebenezer Rabindrarajan, Nagarajan Ramakrishnan, Toby Richards, Guillermo M Ruiz-Palacios, Clark D Russell, Janet T Scott, Malcolm G Semple, Nahoko Shindo, Louise Sigfrid, Emily C Somers, Arshad Taqi, Lance Turtle, Irani Thevarajan, Bharath Kumar Tirupakuzhi Vijayaraghavan, Ishara Udayanga, Sylvie van der Werf, Renaud Vatrinet, Pavan Kumar Vecham, Steve Webb, John Amuasi, Muge Cevik, William Fischer, Tom Fletcher
Journal: The Lancet Infectious Diseases (2020)
The Need for a Tighter Particulate-Matter Air-Quality Standard
Authors: H Christopher Frey, Peter J Adams, John L Adgate, George A Allen, John Balmes, Kevin Boyle, Judith C Chow, Douglas W Dockery, Henry D Felton, Terry Gordon, Jack R Harkema, Patrick Kinney, Michael T Kleinman, Rob McConnell, Richard L Poirot, Jeremy A Sarnat, Lianne Sheppard, Barbara Turpin, Ron Wyzga
Journal: New England Journal of Medicine (2020)
Response to: ‘COVID-19 pandemic: an opportunity to assess the utility of telemedicine in patients with rheumatic diseases’ by Lopez-Medina <i>et al</i>
Authors: Emanuele Bozzalla Cassione, Giovanni Zanframundo, Alessandro Biglia, Veronica Codullo, Carlomaurizio Montecucco, Lorenzo Cavagna
Journal: Annals of the Rheumatic Diseases (2020)

We thank Lopez-Medina et al 1 for their comment on our paper and for sharing their experience with phone consultations.2 Telemedicine, in the past years, has been progressively implemented into medical practice. However, it has not been able to fully take root into routine medical care yet. The COVID-19 pandemic provided the opportunity to take a further step towards the integration between virtual and traditional medical assistance in many medical specialties including rheumatology. The restriction rules, taken over by numerous countries, together with the necessity of assuring a proper continuity of care, have forced us to adopt telemedicine tools in our routine involving chronic patients. To overcome legal matters of privacy and data protection, we have recently set up a …
Drug resistance patterns of Ewing’s Sarcoma Family of Tumor cell lines derived from patients at different phases of therapy
Authors: Rita Grigoryan, Nino Keshelava, Daniel Cabral, C. Reynolds
Journal: Cancer Research (2008)

3756  Despite aggressive chemotherapy and radiotherapy, 30% to 50% of patients with Ewing’s Sarcoma Family of Tumors (ESFT) almost invariably die of their disease. To expand preclinical testing for ESFT, the Children9s Oncology Group has established an ESFT preclinical testing lab (www.ESFTlab.org). We hypothesize that cell line models reflecting the drug resistance of patient tumors will enable development of new therapeutic modalities. To determine whether ESFT cell lines acquire a sustained drug-resistance to those drugs clinically used for treating ESFT, we studied newly established ESFT cell lines derived from different points in therapy: two at diagnosis (CHLA-9, CHLA-32), three after chemotherapy and progressive disease (CHLA-10, CHLA-25, CHLA-56), and two at relapse after autologous bone marrow transplantation (post-ABMT) (CHLA-258, CHLA-352). The well-studied TC-71, TC-32, SK-N-MC, and A-673 ESFT cell lines were also included. All cell lines were unique by short tandem repeat assay. The in vitro dose-response curves of melphalan (L-PAM), cyclophosphamide (as 4-HC), carboplatin (CBDCA), topotecan (TPT), etoposide (ETOP), irinotecan (as SN-38), vincristine (VINC), and doxorubicin (DOX) were determined by the DIMSCAN cytotoxicity assay. Overall, the drug resistance of ESFT cell lines tended to increase with the intensity of therapy delivered clinically prior to cell line initiation. IC99 values were generally greater for post-therapy cell lines. The most chemo-resistant cell lines were the post-ABMT cell lines. These data suggest that, as for neuroblastoma cell lines, the drug resistance profiles of newly established ESFT cell lines reflect their clinical drug exposures. The multidrug-resistant ESFT lines in this panel should prove useful in identifying mechanism of drug resistance and also for testing novel agents that may overcome ESFT drug resistance. Supported by Rett’s Initiative via the National Childhood Cancer Foundation.
FRI0414 FACTORS ASSOCIATED WITH THE IMPACT OF GONARTHROSIS ON MUSLIM PRAYER
Authors: M. Hfaidh, K. Maatallah, H. Ferjani, W. Triki, D. Kaffel, W. Hamdi
Journal: Annals of the Rheumatic Diseases (2020)

Background: Gonarthrosis is a frequent and chronic pathology, which can cause painful functional impotence and limit the performance of activities of daily living[1]. Objectives: This study aimed to assess the patient’s perception of the physical and psychological repercussions of his illness on the practice of prayer and to determine the factors associated with this repercussion. Methods: It was a cross-sectional prospective study conducted in the rheumatology department in 56 patients with gonarthrosis who regularly practiced prayer before the onset of the disease. The socio-demographic data, the clinical characteristics of gonarthrosis were studied and a pre-established questionnaire was offered to patients to assess the physical and psychological impact of gonarthrosis on their prayer practice. Results: Fifty-six patients were included, 83.3% of whom were female. The average age was 56.1 years [38-78 years]. The disease has progressed for an average of 6.14 years [1-13 years]. Gonarthrosis was bilateral in 80.4% of cases. The average body mass index (BMI) was 30.29 kg / m 2 ± 3.061 with extremes ranging from 24 to 36 kg / m 2 . Quadriceps (Q) retraction was noted in 64.28% of cases. Gonarthrisis was classified as stages I, II and III according to the classification of Kellegren and Lawrence in 14.3%, 57.1% and 28.6% of patients respectively. In 71.4% of cases (40 patients), the practice of prayer after the onset of gonarthrosis was considered more difficult with a degree of difficulty of 4.23/10 ± 2. Initial standing was considered possible by all patients. Inclination was possible in 89.2% of patients, whereas it was replaced by sitting on a chair by the rest. Prostration and final sitting station were considered impossible by 64.3% of patients and were therefore performed on chairs (36 patients). The limiting factor cited by patients was pain in 100% of cases. A psychological impact was reported in 53.6% of cases. It was explained by the feeling of guilt in 22 cases, the relatives’ comments in 8 cases and the suffering related to disability in 7 cases. Prayer position was associated with Q retraction (p = 0.001) and knee pain seniority (6.81 ± 3.608vs4.95 ± 3.017, p = 0.05). The degree of difficulty was associated with the BMI (p = 0.013), knee pain seniority (p &lt;0.001) and Q retraction (5.74 ± 1.851 vs 3.46 ± 1.789, p &lt;0.001). Conclusion: Prayer is an activity that is part of the daily lives of many Muslim patients, its evaluation should be considered as one of the elements of the quality of life and functional impact of gonarthrosis. References: [1]Leclerc L, Rossignol M. Retentissement fonctionnel de l’arthrose: résultats d’une enquête nationale effectuée auprès de 10000 patients consultant pour arthrose. Rev Rhum Ed Fr. 2005;5:404-10. Disclosure of Interests: None declared
Increased all-cause mortality in newly diagnosed patients with heart failure between 2006 and 2012 : a retrospective, population-based study in Sweden
Authors: K. Lindmark, K. Boman, M. Olofsson, S. Bruce Wirta, C. C. Proenca, A. Levine, A. Castelo-Branco, Jan Stålhammar, Gerhard Wikström
Journal: European Journal of Heart Failure (2018)
The global burden and attributable risk factor analysis of acute myeloid leukemia in 195 countries and territories from 1990 to 2017: estimates based on the global burden of disease study 2017
Authors: Ming Yi, Anping Li, Linghui Zhou, Qian Chu, Yongping Song, Kongming Wu
Journal: Journal of Hematology & Oncology (2020)

Acute myeloid leukemia (AML) is a common leukemia subtype and has a poor prognosis. The risk of AML is highly related to age. In the context of population aging, a comprehensive report presenting epidemiological trends of AML is evaluable for policy-marker to allocate healthy resources.This study was based on the Global Burden of Disease 2017 database. We analyzed the change trends of incidence rate, death rate, and disability-adjusted life year (DALY) rate by calculating the corresponding estimated annual percentage change (EAPC) values. Besides, we investigated the influence of social development degree on AML's epidemiological trends and potential risk factors for AML-related mortality.From 1990 to 2017, the incidence of AML gradually increased in the globe. Males and elder people had a higher possibility to develop AML. Developed countries tended to have higher age-standardized incidence rate and death rate than developing regions. Smoking, high body mass index, occupational exposure to benzene, and formaldehyde were the main risk factors for AML-related mortality. Notably, the contribution ratio of exposure to carcinogens was significantly increased in the low social-demographic index (SDI) region than in the high SDI region.Generally, the burden of AML became heavier during the past 28 years which might need more health resources to resolve this population aging-associated problem. In the present stage, developed countries with high SDI had the most AML incidences and deaths. At the same time, developing countries with middle- or low-middle SDI also need to take actions to relieve rapidly increased AML burden.