tbuckley/cabot-search huggingface dataset:
SP0056 MAPPING GENES TO IMMUNE CELLS
Authors: Kazuhiko Yamamoto
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Many disease susceptibility variants have been recently identified by genome wide association study (GWAS). Germline genetic variations exist before the disease onset and provide us with evidence into the causal relationship of the observed phenomenon and their pathogenesis. In this regards, the majority of GWAS risk variants have been found to function as an expression-quantitative trait locus (e-QTL). <h3>Objectives:</h3> We need functional studies aiming at determining the causal genetic variants uncovered by GWAS and finding biological mechanisms underlying the observed statistical associations. <h3>Methods:</h3> We established a system to evaluate various subtypes of leukocytes from peripheral blood mononuclear cells (PBMC) from healthy individuals. PBMC are separated with a fluorescence activated cell sorter and are analyzed in a steady state or activated conditions to capture the dynamic responses of gene regulation. Genotyping, RNA-seq, assay for transposase-accessible chromatin using sequencing (ATAC-seq) are performed on each subset. To further investigate the genetic determinants of promotor and enhancer activities, we also perform Cap Analysis of Gene Expression (CAGE) on the corresponding samples. CAGE is a technology developed in our research center RIKEN in Japan. It relies on random priming and cap-trapping of cDNAs to capture the 5"ends of both polyadenylated and non- polyadenylated RNA transcripts. It thus enables genome-wide identification of transcription start sites (TSSs), which could be used as a portal to annotate and measure the activity of promoters and enhancers (Carninci P. et al Science 2005, Forrest ARR. et al Nature 2014 and other publications of the FANTOM project). Using CAGE, we can map the promoters, enhancers and lncRNAs active in each leukocyte subtypes and correlate their activities with genetic variants. <h3>Results:</h3> I will present our ongoing data. <h3>References:</h3> [1] Okada Y, et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 2014;506:376-381. [2] Ishigaki K, et al. Polygenic burdens on cell-specific pathways underlie the risk of rheumatoid arthritis. Nat Genet 2017;49:1120-1125. <h3>Disclosure of Interests:</h3> Kazuhiko Yamamoto Grant/research support from: Astellas, BMS, Daiichi-Sankyo, Mitsubishi Tanabe, Pfizer, Ayumi, Takeda, Chugai, Eisai, Taisho Toyama, UCB, Janssen, Eli Lilly, and NIPPON KAYAKU., Speakers bureau: Astellas, BMS, Daiichi-Sankyo, Mitsubishi Tanabe, Pfizer, Ayumi, Takeda, Chugai, Eisai, Taisho Toyama, UCB, Janssen, Eli Lilly, and NIPPON KAYAKU.
Bayesian Inference of Species Networks from Multilocus Sequence Data
Authors: Chi Zhang, Huw A Ogilvie, Alexei J Drummond, Tanja Stadler
Journal: Molecular Biology and Evolution (2017)

Reticulate species evolution, such as hybridization or introgression, is relatively common in nature. In the presence of reticulation, species relationships can be captured by a rooted phylogenetic network, and orthologous gene evolution can be modeled as bifurcating gene trees embedded in the species network. We present a Bayesian approach to jointly infer species networks and gene trees from multilocus sequence data. A novel birth-hybridization process is used as the prior for the species network, and we assume a multispecies network coalescent prior for the embedded gene trees. We verify the ability of our method to correctly sample from the posterior distribution, and thus to infer a species network, through simulations. To quantify the power of our method, we reanalyze two large data sets of genes from spruces and yeasts. For the three closely related spruces, we verify the previously suggested homoploid hybridization event in this clade; for the yeast data, we find extensive hybridization events. Our method is available within the BEAST 2 add-on SpeciesNetwork, and thus provides an extensible framework for Bayesian inference of reticulate evolution.
Distribution of Industry Payments Among Medical Directors of Catheterization and Electrophysiology Laboratories From the Top 100 US Hospitals
Authors: Amarnath Annapureddy, Prasanna Sengodan, Shiwani Mahajan, Tulasi Annapureddy, Karthik Murugiah, Nihar R. Desai, Jeptha P. Curtis
Journal: JAMA Internal Medicine (2019)

This analysis of 2017 data from the Open Payments Program (OPP) database examines nonresearch industry payments to directors of caronary catheterization and electrophysiology laboratories to characterize payments across 13 OPP-defined categories.
Abstract 19548: Medication Adherence Mediates the Relationship Between Memory and Emergency Room and Hospital Utilization in Patients With Heart Failure
Authors: Anton Vehovec, Mary Dolansky, Joel Hughes, Richard Josephson
Journal: Circulation (2017)

Introduction: Cognitive impairment is prevalent in patients with heart failure HF and is associated with negative outcomes. Poorer adherence to HF medication regimens is associated with increased h...
PF521 CHOP TREATMENT ENHANCES DEPENDENCY ON BCL‐2, MCL‐1 AND BCL‐XL IN DIFFUSE LARGE B‐CELL LYMPHOMA
Authors: M. De Jong, M. Langendonk, B. Reitsma, M. Nijland, G. Huls, A. van den Berg, E. Ammatuna, L. Visser, T. van Meerten
Journal: HemaSphere (2019)

Background: Deregulation of anti‐apoptotic proteins BCL‐2, MCL‐1, BCL‐XL or BCL‐W is often a contributing factor to oncogenic transformation or progression, including in diffuse large B‐cell lymphoma (DLBCL). Gene expression profiling and immunohistochemistry analysis has shown overexpression of BCL‐2 in DLBCL is an important adverse prognostic factor, and has been correlated to resistance of standard therapy composed of cyclophosphamide, vincristine, doxorubicin, prednisolone and the anti‐CD20 antibody rituximab (R‐CHOP). Although these studies show a clear relation between BCL‐2 and therapy response, at the moment it remains unclear what the effect is of CHOP therapy on the intracellular anti‐apoptotic dependency in DLBCL. Aims: Here, we aim to determine the effect of CHOP treatment on the anti‐apoptotic proteins by employing BH3 profiling and investigate whether CHOP treatment enhances sensitivity for BH3 mimetic drugs. Methods: We first investigated the predictive value of anti‐apoptotic gene expression in 1800 DLBCL patients treated with CHOP or R‐CHOP. Next, dynamic BH3 profiles were acquired for 8 DLBCL cell lines treated with CHOP for 18 hours. Validation experiments were performed for CHOP combined with BH3 mimetic drugs on selected DLBCL cell lines. Finally, individual CHOP components were tested using BH3 profiling. Results: Gene expression analysis of anti‐apoptotic proteins revealed BCL‐2 had a significant negative association with survival in DLBCL patients, which was not observed for MCL‐1, BCL‐XL or BCL‐W. Analysis of anti‐apoptotic proteins expression in DLBCL cell lines demonstrated a strong adverse correlation for BCL‐2 protein expression and venetoclax (BCL‐2i) sensitivity, and a strong positive correlation for BCL‐2 protein expression and CHOP sensitivity. Dynamic BH3 profiling of CHOP‐treated DLBCL cell lines showed CHOP was able to enhance dependency on MCL‐1, BCL‐XL and BCL‐2. Validation experiments with BH3 mimetic drugs confirmed cell line specific enhanced sensitivity for S63845 (MCL‐1i), venetoclax (BCL‐2i) and/or navitoclax (BCL‐2/BCL‐XL/BCL‐Wi). No sensitivity‐related changes were observed on anti‐apoptotic protein expression after CHOP treatment. Dynamic BH3 analysis of single CHOP components revealed doxorubicin and vincristine were able to induce changes that were similar to the dynamic CHOP‐treated profiles. Summary/Conclusion: Gene expression analysis confirm that BCL‐2 status is a treatment‐independent predictive factor for DLBCL survival. However, our results demonstrate that CHOP treatment also induces cell‐specific increased anti‐apoptotic dependency on MCL‐1 or BCL‐XL, and not just BCL‐2. These results provide new perspective for the treatment of CHOP‐resistant DLBCL and underline the potential of BH3 profiling in predicting therapy outcome. image
PF574 TARGETED ULTRA‐DEEP NGS ASSESSMENT OF TP53 MUTATIONS IN MULTIPLE MYELOMA FROM WHOLE BONE MARROW
Authors: A. Petrackova, L. Sedlarikova, J. Minarik, M. Vasinek, T. Dyskova, H. Urbankova, J. Bacovsky, T. Papajik, E. Kriegova
Journal: HemaSphere (2019)

Background: Among the most important prognostic genetic aberrations in multiple myeloma (MM) are del(17p) and/or TP53 mutations. The use of the whole bone marrow (BM), when sorted MM cells are not available, may greatly simplify the NGS assessment in MM patients for clinical decisions. Aims: Therefore, the objective of our study was to assess applicability of ultra‐deep targeted NGS for analysis of TP53 mutations and other commonly mutated genes NRAS, KRAS and BRAF using the whole BM samples and compare it to results from MM sorted cells. Methods: BM samples were obtained from MM patients (n = 35, 12 M/23 F). The gDNA was isolated from whole BM (infiltration of plasma cells: median 16.4%, min‐max 1.2 ‐ 65.6%) and paired sorted MM cells. The full coding sequence and 5́and 3́UTR regions of the TP53 gene and hotspots of NRAS , KRAS and BRAF were analysed using ultra‐deep NGS with the MiSeq system (Illumina). The cut‐off for mutation detection was 1% variant allele frequency (VAF), the binomial distribution equation was used to determine a minimum number of mutant alleles. Results: Of MM patients, 22.9% (8/35) harboured mutations in TP53 gene, 20.0% (7/35) KRAS, 14.3% (5/35) NRAS and 8.6% (3/35) BRAF in the whole BM. In all patients, the VAF was in accordance with plasma cells infiltration in BM. Regarding TP53 , five patients carried only TP53 mutations, two had a co‐occurrence of TP53 mutations and del(17p) and one had TP53 mutation together with 17chr trisomy as assessed by FISH . In TP53, all of the mutations except one case were observed with low frequency (VAF 2–9%). In cases when paired sorted sample was available, the mutations found in the whole BM were confirmed in sorted MM cells. Summary/Conclusion: Our results demonstrate the applicability of ultra‐deep targeted NGS in assessment of TP53 mutations in the whole BM samples in MM when sorted population is not available. Moreover, our data highlights the importance of assessment of TP53 mutations in MM patients, as they may occur regardless of del(17p). Our approach may simplify the assessment of mutational landscape in MM patients and thus impacts clinical decision making. Grant support: MZ ČR VES16–32339A, IGA UP_2019_014, MH CZ–DRO (FNOL, 00098892), NV18–03‐00500
An Atlas of Genetic Variation Linking Pathogen-Induced Cellular Traits to Human Disease
Authors: Liuyang Wang, Kelly J. Pittman, Jeffrey R. Barker, Raul E. Salinas, Ian B. Stanaway, Graham D. Williams, Robert J. Carroll, Tom Balmat, Andy Ingham, Anusha M. Gopalakrishnan, Kyle D. Gibbs, Alejandro L. Antonia, Joseph Heitman, Soo Chan Lee, Gail P. Jarvik, Joshua C. Denny, Stacy M. Horner, Mark R. DeLong, Raphael H. Valdivia, David R. Crosslin, Dennis C. Ko
Journal: Cell Host & Microbe (2018)
Abstract P334: Blood Pressure Salt Sensitivity Influences Plasma Glucose Response to Dietary Sodium and Potassium Intervention
Authors: Shengxu Li, Lydia A Bazzano, Dongfeng Gu, Qi Zhao, Jing Chen, Tanika Kelly, Chung-Shiuan Chen, Jian-Feng Huang, Ji-chun Chen, Jie Cao, Jianxin Li, L. Lee Hamm
Journal: Circulation (2013)

We studied the association between blood pressure salt sensitivity and plasma glucose responses to dietary sodium intervention among 1,906 GenSalt (Genetic Epidemiology Network of Salt Sensitivity)...
A Cultural Context for Providing Dermatologic Care to American Indian and Alaskan Native Communities Through Telehealth
Authors: Lucinda L. Kohn, Camille E. Introcaso
Journal: JAMA Dermatology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Abstract 9992: Rhythm Control Versus Rate Control and Clinical Outcomes in Patients With Atrial Fibrillation: Results From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF)
Authors: Amit Noheria, Peter Shrader, Jonathan P Piccini, Gregg C Fonarow, Peter R Kowey, Kenneth W Mahaffey, Gerald Naccarelli, Peter A Noseworthy, James A Reiffel, Benjamin A Steinberg, Laine E Thomas, Eric D Peterson, Bernard J Gersh
Journal: Circulation (2015)

Introduction: Randomized trials have not demonstrated significant differences in stroke, heart failure or mortality between rhythm and rate control strategies for management of atrial fibrillation (AF). The comparative outcomes in contemporary clinical practice are not well described. The objective of this study was to evaluate outcomes in clinical practice with rhythm control versus rate control strategy. Methods: Patients managed with a rhythm control strategy targeting maintenance of sinus rhythm were retrospectively compared with a strategy of rate control alone in a AF registry across various US practice settings. Unadjusted and adjusted (inverse-propensity weighted) outcomes were estimated. Results: The overall study population (n=6988) had a median age of 74 (25th, 75th percentile 65, 81) years, 56% were males, 77% had first detected or paroxysmal AF and 89% had CHA2DS2-VASc score ≥2. In unadjusted analyses, rhythm control was associated with lower all-cause death, cardiovascular death, first stroke/non-central nervous system systemic embolization/transient ischemic attack, or first major bleeding event (all p&lt;0.05); however, rhythm control was associated with more cardiovascular hospitalizations (HR 1.24, 95% CI 1.10-1.39, p=0.0003; Figure). Conclusion: Among patients with AF in clinical practice, rhythm control was not superior to rate control strategy for outcomes of stroke, heart failure, or mortality, but was associated with more cardiovascular hospitalizations.
pH- and photothermal-driven multistage delivery nanoplatform for overcoming cancer drug resistance
Authors: Wenjing Huang, Hao Zhao, Jiangshan Wan, Yang Zhou, Qingbo Xu, Yanbing Zhao, Xiangliang Yang, Lu Gan
Journal: Theranostics (2019)

Reversing multidrug resistance (MDR) remains a big challenge in cancer therapy.Combining the hyperthermia and chemotherapy is a promising strategy for efficient cancer treatment with MDR reversal.Gold nanocages (GNCs) are an ideal photothermal (PTT)-chemotherapy integration platform due to their good photothermal conversion efficiency and the unique hollow interiors.However, insufficient tumor cell internalization and in vivo premature drug leakage restrict the anticancer activity of GNCs-based drug delivery systems.Methods: pH low insertion peptide (pHLIP)-and thermoresponsive poly(di(ethylene glycol) methyl ether methacrylate-co-oligo(ethylene glycol) methyl ether methacrylate) polymer-conjugated GNCs were rationally constructed to load anticancer drug doxorubicin (DOX@pPGNCs).Tumor acidic environment-responsive tumor cell internalization, and near-infrared (NIR) laser-induced tumor accumulation, penetration and on-demand drug release were systematically examined.Results: DOX@pPGNCs display good photothermal efficacy and thermoresponsive property.NIR laser irradiations at the tumor site significantly enhance tumor accumulation and penetration.Once DOX@pPGNCs reach the tumor site, the conformational transformation of pHLIP at the acidic tumor microenvironment contributes to the enhanced cellular internalization.Furthermore, NIR laser-triggered photothermal effects induce the shrinkage of thermoresponsive polymer, resulting in the opening of the pores of GNCs and a rapid intracellular DOX release to the nuclei.DOX@pPGNCs exhibit synergistic antitumor effect with MDR reversal in vitro and in vivo.Conclusion: DOX@pPGNCs present strong potential to overcome MDR in cancer.
AB1210 SOCIAL MEDIA USE IN RHEUMATOLOGY PATIENTS
Authors: Mustafa Erdogan, Okan Aydin, Emire Seyahi
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The impact of social media on individual or institutional communication and knowledge acquisition is non-negligible. Whether patients (patients) with rheumatic diseases share information about their health on social media is unknown. <h3>Objectives</h3> We aimed to investigate how often and to what extent patients with a rheumatic condition use social media. We also wanted to know whether they communicate with their doctors through social media and what their expectations are. <h3>Methods</h3> Consecutive patients with diverse diagnoses attending a rheumatology outpatient clinic were studied. Patients completed a self-administered questionnaire (1) which was modified. Information on demographic features, educational status and diagnosis was also recorded. <h3>Results</h3> 397 patients completed the questionnaire (Table). 329 patients with devices, 40 (12%) of these patients were not using social media. 68 patients without devices, thus social media users reached 73% (289/397). While, Facebook users and non-users were similar according to age, gender or educational status, Twitter users were more likely to be male and more educated (Figure). 96% were willing to communicate with their doctors through one of the social media sources. 75% desired to be friends with their rheumatologist on the Facebook. When we asked, "why would you like to communicate with your rheumatologist?"; The majority (39%) responded that it would be easier to understand each other;% 32 thought that they would feel more connected,% 27 thought that their rheumatologist would be more responsible 21% thought that their disease will get better. <h3>Conclusion</h3> This survey showed that younger and more educated patients had significantly more communication devices. Facebook was the most preferred social media website. More educated patients prefer using Twitter, Instagram and Pinterest and younger patients Instagram and Pinterest. The majority thought that social media was a useful information source about health. While only 23% had an actual connection with their rheumatologist through social media, 75% desired to be friends on the Facebook. <h3>References</h3> [1] Hausmann, Jonathan S., et al. "Adolescent and young adult use of social media for health and its implications." Journal of Adolescent Health 60.6 (2017): 714-719. <h3>Disclosure of Interests</h3> None declared
THU0457 EVALUATION OF THE EFFECTIVENESS OF COMPLEX TREATMENT OF OBESITY ON THE CLINICAL MANIFESTATIONS OF KNEE OSTEOARTHRITIS AND THE DYNAMICS OF CYTOKINES, DEPENDING ON THE DEGREE OF WEIGHT LOSS
Authors: Ekaterina Strebkova, Ludmila Alekseeva
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Obesity is a risk factor and progression of the metabolic phenotype of osteoarthritis (OA). The decrease in body weight is important in the treatment of OA. Non-drug therapy aimed at altering the eating behavior, allows you to achieve a decrease in body weight of only 5%, which does not always contribute to the achievement of the clinical effect in patients with diseases of the joints. <h3>Objectives:</h3> Assess the effectiveness of complex treatment of obesity with the use of orlistat (intestinal lipase inhibitor) on the clinical manifestations of the knee OA and the dynamics of cytokines (CRP, IL-6, TNF-α) depending on the degree of weight loss. <h3>Methods:</h3> 50 female patients (45-65 y.o.) with Kellgren-Lawrence stage II-III KOA and obesity (BMI&gt;30kg/m²). Patients in Group 1 (n = 25) took 120 mg of orlistat 3 times a day in combination with a low-calorie diet and exercise for 6 months. Patients in Group 2 (n = 25) were recommended non-drug therapy for obesity for 6 months. At baseline and after 6 months, the clinical parameters of the knee OA (WOMAC) were evaluated, the quality of life was assessed (EQ-5D). A laboratory study of peripheral blood was conducted at baseline and after 6 months: CRP, IL-6, TNF-α. <h3>Results:</h3> After 6 months of complex treatment of obesity with the use of orlistat, patients in Group 1 achieved a significant weight loss of 10.07% (p &lt;0.05). Depending on the degree of weight loss in Group 1, 15 patients lost&gt; 10% and 10 patients lost 5–9.9% of the initial body weight. In the 2nd group, an insignificant weight loss of 0.84% (p&gt; 0.05) was achieved, all patients in Group 2 lost less than 5%. Depending on the degree of weight loss, it is noted that in patients with weight loss more than 5% better than WOMAC (pain, stiffness, functional state) (p &lt;0.05), EQ-5D (p &lt;0.05) compared with less weight loss. In patients with weight loss&gt; 10%, a significant decrease in CRP level was observed (p = 0.03) (Fig. 1) compared with baseline and patients with a 5–9.9% weight loss (p = 0.03) and &lt;5% (p = 0.02). Data for statistically significant changes from TNF-α and IL-6, depending on the degree of weight loss was not detected. <h3>Conclusion:</h3> The results of the study demonstrated a significant effectiveness of the complex treatment of obesity in patients with knee OA, compared with the use of only non-pharmacological methods of weight loss. A decrease in body mass of more than 5% helps to improve the clinical manifestations of knee OA and the quality of life of patients. A decrease in body weight of more than 10% demonstrates a decrease in the level of CRP, which suggests an effect on meta-inflammation in OA. <h3><b>Disclosure of Interests:</b></h3> Ekaterina Strebkova: None declared, Ludmila Alekseeva Speakers bureau: Bayer, Boeringer-ingelheim, Gedeon-Richter, Servier&nbsp;