tbuckley/cabot-search huggingface dataset:
FRI0018 ASSOCIATION OF MICRORNA-146A RS57095329 POLYMORPHISM WITH SUSCEPTIBILITY TO GOUT TOPHI IN A CHINESE HAN POPULATION
Authors: Yu-Feng Qing, Ting Yi, Zi-Yi Tang, Jian-Xiong Zheng, Qin Xiong, Quan-Bo Zhang
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> MicroRNA-146a (miR-146a) plays an important role in regulation of autoinflammatory diseases including gout[1]. Growing evidences have demonstrated that association of miR-146a gene single nucleotide polymorphisms (SNPs) with risk of several diseases[2], but no genetic relevance studies of miR-146a gene polymorphisms to gout have been reported by now. <h3>Objectives</h3> To investigate the potential association of gout and the functional rs57095329 SNP of miR-146a in the Chinese Han population. <h3>Methods</h3> The rs57095329 SNP was detected in 448 primary gout patients (containing 76 tophi patients) and 418 healthy control subjects. Peripheral blood mononuclear cells (PBMCs) miR-146a expression was measured in 81 gout patients (including 32 tophi patients and 49 non-tophi patients) and 47 healthy subjects. <h3>Results</h3> No significant difference was detected in the distribution of miR-146a rs57095329 between 448 gout patients and 418 healthy subjects (P&gt;0.05). However, significant differences were observed between 76 gout with tophi patients and 418 healthy subjects, between gout with tophi (76) and with no tophi patients (372) both in genotypes and allele distributions (P&lt;0.01, respectively). Gout patients carrying AG/GG genotypes had a 0.323-fold reduced risk for tophi than those carrying AA genotype, and the G allele carrier of gout patients had a 0.362-fold reduced risk for tophi. Additionally, GG genotype was significantly associated with increased expression of miR-146a in 32 tophi patients (Figure). <h3>Conclusion</h3> Our study shows a novel, significant association between the miR-146a rs57095329 polymorphism and a lower risk of tophi in gout patients. Furthermore, our findings suggest that this gene polymorphism might affect the genetic predisposition to tophi development and modulate the expression of miR-146a level in tophi patients. This new knowledge about miR-146a may be clinically important and confirms a role for miR-146a in the pathophysiology of tophi, with potentially important therapeutic implications. <h3>References</h3> [1] Zhang QB, Qing YF, Yin CC, Zhou L, Liu XS, Mi QS, et al. Mice with miR-146a deficiency develop severe gouty arthritis via dysregulation of TRAF 6, IRAK 1 and NALP3 inflammasome. Arthritis Res Ther. 2018;20:45. [2] Luo X, Yang W, Ye DQ, Cui H, Zhang Y, Hirankarn N, et al. A functional variant in microRNA-146a promoter modulates its expression and confers disease risk for systemic lupus erythematosus. PloS Genet. 2011;7:e1002128. <h3>Disclosure of Interests</h3> Yu-Feng Qing Grant/research support from: Sichuan Youth Science and Technology (2016JQ0053), and the Department of Science and Technology of Sichuan Province (2018JY0257), Ting Yi: None declared, Zi-Yi Tang: None declared, Jian-Xiong Zheng: None declared, Qin Xiong: None declared, Quan-Bo Zhang: None declared
Treatment with Statins Does Not Revert Trained Immunity in Patients with Familial Hypercholesterolemia
Authors: Siroon Bekkering, Lotte C.A. Stiekema, Sophie Bernelot Moens, Simone L. Verweij, Boris Novakovic, Koen Prange, Miranda Versloot, Jeanine E. Roeters van Lennep, Henk Stunnenberg, Menno de Winther, Erik S.G. Stroes, Leo A.B. Joosten, Mihai G. Netea, Niels P. Riksen
Journal: Cell Metabolism (2019)
Preclinical pharmacokinetic studies with s-HDAC-42 (NSC 736012), an inhibitor of histone deacetylase, by LC-MS/MS
Authors: Hao Cheng, Zhongfa Liu, Samuel K. Kulp, Ching-Shih Chen, Joseph M. Covey, Kenneth K. Chan
Journal: Cancer Research (2006)

3091  Purpose. R, S-HDAC-42 (NSC 731438), an inhibitor of histone deacetylase, has been found to possess potent cytotoxicity in the NCI 60-cell line screen with a mean GI50 of 0.2 μM. The S-enantiomer of HDAC-42 (s-HDAC-42; NSC 736012) is the more potent isomer. The purpose of this study was to develop a highly sensitive LC-MS assay for the analysis of s-HDAC-42 in plasma and to characterize its pharmacokinetics in mice. Methods. A liquid chromatograph-triple quadrupole mass spectrometer (LC-MS) with electrospray (ESI) ionization was used for quantification. Plasma (0.1 mL) was spiked with s-HDAC-42 and the internal standard, hesperetin and then extracted with ethyl acetate. The extracts were subjected to ESI LC-MS using a BetaBasic C8 column with isocratic elution. Positive ion selected reaction monitor (MRM) mode with ion transitions at m/z 313.2-133.2 for s-HDAC-42 and m/z 303.2-177.2 for hesperetin was used for quantification. The assay method was validated in mouse plasma. Pharmacokinetics (PK) of s-HDAC-42 in CD1F2 mice was studied following i.v. bolus administration at 20 mg/kg and p.o dose at 50 mg/kg. Results. The Lower limit of quantification (LLOQ) for s-HDAC-42 was found to be 2 ng/ml (6 nM), in mouse plasma. Linearity was demonstrated between the LLOQ to 1000 ng/mL (3.2 μM). The within-day coefficients of variation (CVs) were found to be 14.7%, 9.5%, and 6.6% at 2, 5, 50 ng/mL (0.006, 0.016, 0.16 μM), the lower concentration range, while 6.1%, 6.0%, and 1.8% at 50, 500, 1000 ng/mL (0.16, 1.6, 3.2 μM), the higher range of concentration (n=6). The corresponding between-day CVs were found to be 8.8, 8.8, 0.6, 8.2, 1.4 and 0.6%, respectively. Plasma protein-binding of s-HDAC-42 was 95-98% at low μM range. Following an i.v. bolus dose at 20 mg/kg, plasma concentration reached ∼49 μM then decreased to 0.02 μM at 48 hr. The data were found to fit to a two-compartment model with an initial and terminal half life of 0.38 hr and 10.1 hr, respectively. The AUC value was 43.7 μM.hr and the total body clearance was 1.47 L/h/kg at 20 mg/kg. s-HDAC-42 was absorbed rapidly following a 50 mg/kg p.o. dose and plasma concentration reached 14.7 μM at 0.17 h and also declined biexponentially with time. The oral bioavailability was found to be 27.4%. Conclusion. An ESI LC-MS/MS method for s-HDAC-42 in plasma with low nM sensitivity has been developed and used to characterize the pharmacokinetics of s-HDAC-42 in mice. Oral absorption was rapid and bioavailability was moderate. In support of RAID #276 (C-S Chen) through NCI-N01-CM-52205.
Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma
Authors: Ana C. deCarvalho, Hoon Kim, Laila M. Poisson, Mary E. Winn, Claudius Mueller, David Cherba, Julie Koeman, Sahil Seth, Alexei Protopopov, Michelle Felicella, Siyuan Zheng, Asha Multani, Yongying Jiang, Jianhua Zhang, Do-Hyun Nam, Emanuel F. Petricoin, Lynda Chin, Tom Mikkelsen, Roel G. W. Verhaak
Journal: Nature Genetics (2018)
Correspondence - ''Telemonitoring in Patients with Heart Failure''
Authors: Sally Inglis, Robyn Clark, John Cleland
Journal: New England Journal of Medicine (2011)

To the Editor: Chaudhry et al. suggest that enhanced support in the use of a telephone-based interactive voice-response system for patients recently discharged after worsening heart failure does not improve outcomes. This finding is broadly consistent with previous systematic reviews of telephone support1 and contrasts with the substantial effect observed with home telemonitoring of vital signs in similar populations.1 The treatment of patients in the control group was excellent, but unrepresentative of usual clinical care and not inferior to the treatment of patients receiving enhanced support. Monitoring alone is unlikely to improve outcomes but may do so when it improves prescription of or adherence to lifesaving treatments. Given enough resources, traditional methods for delivering care may render an interactive voice-response system or a home telemonitoring system ineffective. Nonetheless, there may be more cost-efficient approaches to ensuring quality care.2 Informal post hoc addition of these data to our recent meta-analysis of telephone support1 does not substantially alter the point estimates for death from any cause or heart-failure−related hospitalizations, but it does nullify the small benefit in hospitalizations for any cause, which may not be reduced by a heart-failure−focused intervention.1 Original article: Telemonitoring in Patients with Heart Failure NEJM. December 9, 2010 | S.I. Chaudhry and Others
Genetic Heterogeneity in Depressive Symptoms Following the Death of a Spouse: Polygenic Score Analysis of the U.S. Health and Retirement Study
Authors: Benjamin W. Domingue, Hexuan Liu, Aysu Okbay, Daniel W. Belsky
Journal: American Journal of Psychiatry (2017)

Objective: Experience of stressful life events is associated with risk of depression. Yet many exposed individuals do not become depressed. A controversial hypothesis is that genetic factors influence vulnerability to depression following stress. This hypothesis is often tested with a “diathesis-stress” model, in which genes confer excess vulnerability. The authors tested an alternative formulation of this model: genes may buffer against depressogenic effects of life stress. Method: The hypothesized genetic buffer was measured using a polygenic score derived from a published genome-wide association study of subjective well-being. The authors tested whether married older adults who had higher polygenic scores were less vulnerable to depressive symptoms following the death of their spouse compared with age-matched peers who had also lost their spouse and who had lower polygenic scores. Data were analyzed from 8,588 non-Hispanic white adults in the Health and Retirement Study (HRS), a population-representative longitudinal study of older adults in the United States. Results: HRS adults with higher well-being polygenic scores experienced fewer depressive symptoms during follow-up. Those who survived the death of their spouses (N=1,647) experienced a sharp increase in depressive symptoms following the death and returned toward baseline over the following 2 years. Having a higher well-being polygenic score buffered against increased depressive symptoms following a spouse’s death. Conclusions: The effects were small, and the clinical relevance is uncertain, although polygenic score analyses may provide clues to behavioral pathways that can serve as therapeutic targets. Future studies of gene-environment interplay in depression may benefit from focus on genetics discovered for putative protective factors.
SP0029 RHEVITAL: CONTROLLING YOUR DISEASE ACTIVITY WITH AN APP
Authors: Corinna Elling-Audersch
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease requiring long-term treatment with regular monitoring of the ongoing therapeutic process by a rheumatologist to achieve good health outcomes and prevent negative disease impacts. <h3>Objectives:</h3> The RheVITAL App is the product of a new and multilayered concept of treatment. A combination of a team of rheumatologists, physiotherapists, IT specialists and research partners from the German League against Arthritis have all contributed to the development of this research project. <h3>Methods:</h3> The presentation will show how this monitoring system improves the treatment of RA individually, monitors the patients on their way to self<b>-</b>empowerment and promotes participative collaboration between patients and rheumatologists. <h3>Results:</h3> The patients play an active role in the whole system. The patients are trained about their diseases, their treatment and the medicine they are taking. Furthermore they are given much more information about the German patient organisation. <h3>Conclusion:</h3> My talk will consider the function and management of the app, the difficulties as well as the efforts of data security and the role of the patient organisation as a research partner involved in this project. <h3>Disclosure of Interests:</h3> None declared
SAT0292 SELF-ADMINISTERED VERSUS INTERVIEW BASED INTERNATIONAL CONSENSUS CRITERIA FOR THE DIAGNOSIS OF RAYNAUD’S PHENOMENON QUESTIONNAIRE – A SINGLE CENTRE EXPERIENCE
Authors: Jaka Ostrovrsnik, Martina Plešivčnik Novljan, Alojzija Hocevar, Matija Tomsic, Ziga Rotar
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> International Consensus Criteria for diagnosing Raynaud's Phenomenon (RP) have been proposed recently (1). These criteria are based on the three-step conditional approach (i.e. a screening question, assessment of colour changes and an item of disease score calculation). It is unclear whether differences exist between the self-administered and interview-based way of questionnaire fulfilment. <h3>Objectives</h3> We aimed in our study to evaluate the two approaches in patients with suspected RP. <h3>Methods</h3> This cross-sectional study was conducted at our secondary/tertiary rheumatology centre between 1 October 2018 and 31 December 2018. Each patient referred for the video capillaroscopy was asked to complete the RP questionnaire on the day of the referral. The same questionnaire was applied as an interview by the rheumatologist before the video capillaroscopy. Differences in answers and level of individual agreement on individual three items, as well as the result of the questionnaire, between the two ways of questionnaire completion were assessed with Fisher exact test and Kappa coefficient, respectively. <h3>Results</h3> During the 3-month period we included 84 consecutive patients (88.1% female, median age (IQR) 49.5 (41.9–56.5) years). Results of answers to each item, final outcome of the questionnaire and the level of individual agreement for each item are presented in Table 1. <h3>Conclusion</h3> Overall, there was a substantial level of agreement between self-administered and interview-based application of International Consensus Criteria for the Diagnosis of Raynaud's Phenomenon questionnaire. However, we observed that the patients were inclined to score the severity of their RP lower than the physicians. <h3>Reference</h3> [1] Maverakis E, Patel F, Kronenberg DG, Chung L, Fiorentino D, Allanore Y, et al. International consensus criteria for the diagnosis of Raynaud's phenomenon. J Autoimmun2014;48–49:60–5. <h3>Disclosure of Interests</h3> None declared
Adopting machine learning to automatically identify candidate patients for corneal refractive surgery
Authors: Tae Keun Yoo, Ik Hee Ryu, Geunyoung Lee, Youngnam Kim, Jin Kuk Kim, In Sik Lee, Jung Sub Kim, Tyler Hyungtaek Rim
Journal: npj Digital Medicine (2019)

Recently, it has become more important to screen candidates that undergo corneal refractive surgery to prevent complications. Until now, there is still no definitive screening method to confront the possibility of a misdiagnosis. We evaluate the possibilities of machine learning as a clinical decision support to determine the suitability to corneal refractive surgery. A machine learning architecture was built with the aim of identifying candidates combining the large multi-instrument data from patients and clinical decisions of highly experienced experts. Five heterogeneous algorithms were used to predict candidates for surgery. Subsequently, an ensemble classifier was developed to improve the performance. Training (10,561 subjects) and internal validation (2640 subjects) were conducted using subjects who had visited between 2016 and 2017. External validation (5279 subjects) was performed using subjects who had visited in 2018. The best model, i.e., the ensemble classifier, had a high prediction performance with the area under the receiver operating characteristic curves of 0.983 (95% CI, 0.977-0.987) and 0.972 (95% CI, 0.967-0.976) when tested in the internal and external validation set, respectively. The machine learning models were statistically superior to classic methods including the percentage of tissue ablated and the Randleman ectatic score. Our model was able to correctly reclassify a patient with postoperative ectasia as an ectasia-risk group. Machine learning algorithms using a wide range of preoperative information achieved a comparable performance to screen candidates for corneal refractive surgery. An automated machine learning analysis of preoperative data can provide a safe and reliable clinical decision for refractive surgery.
Precore mutation and its relation with HBV-DNA levels, viral genotypes and liver damage in brazilian patients with chronic hepatitis B virus (HBV) infection
Authors: Rosamar E. Rezende, João Renato Rebello Pinho, Dennis A. Bertolini, Marie Secaf, Leandra Naíra Zambelli Ramalho, Sérgio Zucoloto, Sandra Silva Rodrigues, Benedito Antonio Lopes da Fonseca, Ana de Lourdes Candolo Martinelli
Journal: Hepatology (2001)
Incorporating Patient Preferences in Noninferiority Trials
Authors: Sergio A. Acuna, Tyler R. Chesney, Nancy N. Baxter
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
SP0197 CASE 1 PRESENTER: EARLY RA WITH LUNG PROBLEMS IN THE CONTEXT OF BIOLOGICAL TREATMENT
Authors: Ana Milena Millán Arciniegas
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> We present a 77-year-old male patient with a history of former smoker, arterial hypertension and dyslipidaemia, whose diagnosis of Rheumatoid Arthritis was made in July 2017 by arthritis of metacarpophalangeal joints, wrists and knees and positivity for anticyclic citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF). Treatment with Methotrexate and prednisone was started but the patient did not achieve adequate control of joint symptoms, so we decided to add Etanercept to the treatment. A good joint response was obtained but in a follow-up control he explained breathlessness with cough and low grade fever. The chest X- Ray was not conclusive and we decided to perform a high resolution computerized tomography (HRCT) scan. An interstitial involvement was detected and an accurate differential diagnosis was made. <h3>Disclosure of Interests:</h3> None declared
Diagnostic performance of the endoscopic pressure study integrated system (EPSIS): a novel diagnostic tool for gastroesophageal reflux disease
Authors: Haruhiro Inoue, Yuto Shimamura, Enrique Rodriguez de Santiago, Yasutoshi Kobayashi, Masaki Ominami, Yusuke Fujiyoshi, Kazuya Sumi, Haruo Ikeda, Manabu Onimaru, Anastassios C. Manolakis
Journal: Endoscopy (2019)

Abstract Background The endoscopic pressure study integrated system (EPSIS) is a prototypic system for monitoring intragastric pressure (IGP) fluctuations that result from opening of the cardia during gastric distension. The performance of EPSIS for the diagnosis of gastroesophageal reflux disease (GERD) was evaluated. Methods A retrospective analysis was conducted of data prospectively collected over a 2-year period from 59 patients who underwent gastroscopy, EPSIS, and 24-hour pH monitoring. Using a dedicated electronic device and a through-the-scope catheter, maximum IGP (IGPmax) and IGP waveform pattern (uphill/flat) were recorded. Results The optimal IGPmax cutoff was 18.7 mmHg. IGPmax &lt; 18.7 mmHg (sensitivity 74.2 %, 95 % confidence interval [CI] 56.8 – 86.3; specificity 57.1 %, 95 %CI 39.1 – 73.5) and flat pattern (sensitivity 71.0 %, 95 %CI 53.4 – 83.9; specificity 82.1 %, 95 %CI 64.4 – 92.1) were associated with GERD. “Double” EPSIS positivity (IGPmax &lt; 18.7 mmHg and flat pattern) provided maximum specificity (85.7 %, 95 %CI 68.5 – 94.3), whereas “any” EPSIS positivity (IGPmax &lt; 18.7 mmHg or flat pattern) provided maximum sensitivity (80.6 %, 95 %CI 63.7 – 90.8). Maximum specificity and sensitivity for nonerosive reflux disease (NERD) was &gt; 70 %. In multivariate analysis, “double” EPSIS positivity was the strongest predictor of GERD (odds ratio [OR] 16.05, 95 %CI 3.23 – 79.7) and NERD (OR 14.7, 95 %CI 2.37 – 90.8). Conclusion EPSIS emerges as a reliable adjunct to routine gastroscopy for GERD diagnosis, and might prove helpful for the stratification and management of patients with reflux disorders.
AB0697C THE ASSOCIATION OF ANTI-MELANOMA DIFFERENTIATION-ASSOCIATED PROTEIN 5 AND SEASONAL PATTERNS IN ONSET OF IDIOPATHIC INFLAMMATORY MYOPATHIES IN KOREA
Authors: In Seol Yoo, Jinhyun Kim, Seong Wook Kang, Su-Jin Yoo, Seungcheol Shim, Chan Keol Park
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> There was some reports of seasonal association with myopsitis onset. With the discovery of new myositis-specific autoantibodies (MSA), detailed grouping of idiopathic inflammatory myopathies was possible. Therefore, we evaluated the seasonal patterns in the onset of idiopathic inflammatory myositis (IIM) with MSA in Korea. <h3>Objectives:</h3> To evaluate the correlation between MSA and seasonal patterns of IIM in Korea. <h3>Methods:</h3> A total of 90 patients who met the criteria for probable or definite PM or DM and for whom data were collected from 7 referal centers in korea. 16 myositis-specific autoantibodies were detected by immunoblot with patient's serum. Statistical analyses were performed using a Poisson model that assessed associations of sex, MSA, and month of onset of symptoms or month of diagnosis. <h3>Results:</h3> There were no significant seasonal patterns of disease onset in total IIM patients. Among MSAs, anti-synthetase (n=18), anti-transcriptional intermediary factor 1 γ (TIF1γ) (n=13), anti-melanoma differentiation-aasocianted protein 5 (anti-MDA5) (n=12), and anti–signal recognition particle (SRP) (n=12) were analyzed. Among 55 patients with dermatomyositis, patients with anti-MDA5 showed a significant peak in winter (n=12, P=0.05). This seasonal association was significant in women (n =10; P=0.045). Patients with anti–synthetase, anti-TIF1 γ or anti-SRP antibodies did not have a significant seasonal onset patterns. There were no significant seasonal patterns in patients without myositis-specific autoantibodies. <h3>Conclusion:</h3> Patients with anti-MDA5 showed a seasonality of myositis onset, in winter. <h3>Disclosure of interests:</h3> None declared