tbuckley/cabot-search huggingface dataset:
AB1290 VITAMIN D AND PAIN SYNDROME IN BREAST CANCER PATIENTS TREATED WITH ADJUVANT LETROZOLE
Authors: Stefania Sciacca, Nadia Melillo, Francesco Paolo Cantatore
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The third-generation aromatase inhibitors (AIs) have shown a favorable overall risk–benefit profile in the upfront adjuvant therapy of postmenopausal estrogen receptor–positive breast cancer. Breast cancer patients treated with long term AIs experience arthralgias and musculoskeletal aching often described as bone pain, musculoskeletal disorder, arthralgia. <h3>Objectives:</h3> The purpose of this study was to investigate clinical, serological and anamnestic features associated to the joint pain syndrome in non-metastatic breast cancer patients treated with adjuvant AIs. <h3>Methods:</h3> Between June 2017 and December 2017 patients with early stage estrogen receptor–positive breast carcinomas treated with adjuvant letrozole, attending our Rheumatologic clinic to undergo osteoporosis screening, were included. Pre-existing symptoms and clinical, serological and imaging features were evaluated to assess the type of musculoskeletal disorder. <h3>Results:</h3> Among 64 patients included a musculoskeletal syndrome was detected in 46 patients (71.8%), whereas diffuse muscle pain was observed in 42 (65.6%) patients, and 83.3% of them had associated arthritis. Serological, imaging and clinical findings suggested more frequently a seronegative arthritis, whereas few patients developed rheumatoid arthritis and arthritis secondary to a connective tissue disease. A direct correlation between pre-existing autoimmune disease and pain symptoms before cancer diagnosis and risk of developing arthritis under AI therapy was observed. Mean vitamin D levels were significantly lower in patients with diffuse myalgia compared to patients with no diffuse myalgia (11.2±5.8 versus 29.5±10.8 ng/ml; t-test p &lt; 0.0001), suggesting a potential involvement of vitamin D deficiency in diffuse muscle pain. <h3>Conclusion:</h3> The etiology of AI-associated pain syndrome remain unknown, but clinical, serological, imaging data may be useful to identify the true origin of the musculoskeletal syndrome, as well as a detailed anamnestic history may be useful to identify autoimmune predisposing factors. Myalgias and generalized weakness are likely associated with hypovitaminosis D and might be misdiagnosed as fibromyalgia. The management of these patients should become a multispecialistic task. <h3>References</h3> [1] Beckwée D, Leysen L. Prevalence of aromatase inhibitor-induced arthralgia in breast cancer: a systematic review and meta-analysis. Support Care Cancer 2017 May;25(5):1673-1686. [2] Borrie AE,Kim RB. Molecular basis of aromatase inhibitor associated arthralgia: known and potential candidate genes and associated biomarkers. Expert Opin Drug Metb Toxicol. 2017 Feb;13(2):149-156. <h3>Disclosure of Interests:</h3> Stefania Sciacca: None declared, Nadia Melillo: None declared, Francesco Paolo Cantatore Speakers bureau: PFIZER, ROCHE
Assessing the Causal Role of Body Mass Index on Cardiovascular Health in Young Adults
Authors: Kaitlin H. Wade, Scott T. Chiesa, Alun D. Hughes, Nish Chaturvedi, Marietta Charakida, Alicja Rapala, Vivek Muthurangu, Tauseef Khan, Nicholas Finer, Naveed Sattar, Laura D. Howe, Abigail Fraser, Debbie A. Lawlor, George Davey Smith, John E. Deanfield, Nicholas J. Timpson
Journal: Circulation (2018)

Background: Body mass index (BMI) has been suggested to be causally related to cardiovascular health in mid-to-late life, but this has not been explored systematically at younger ages—nor with detailed cardiovascular phenotyping. Recall-by-Genotype (RbG) is an approach that enables the collection of precise phenotypic measures in smaller studies, while maintaining statistical power and ability for causal inference. Methods: In this study, we used a combination of conventional multivariable regression analysis, Mendelian randomization (MR), and subsample RbG methodologies to estimate the causal effect of BMI on gross-level and detailed cardiovascular health in healthy participants from the Avon Longitudinal Study of Parents and Children at age 17 years (N=1420–3108 for different outcomes) and an independent sample from the same cohort (for RbG) study at age 21 years (N=386–418). Results: In both MR and RbG analyses, results suggested that higher BMI causes higher blood pressure and left ventricular mass index in young adults (eg, difference in left ventricular mass index per 1 kg/m 2 using MR: 1.07 g/m 2.7 ; 95% CI, 0.62–1.52; P =3.87×10 -06 and per 3.58 kg/m 2 using RbG: 1.65 g/m 2.7 ; 95% CI, 0.83–2.47; P =0.0001). Additionally, RbG results suggested a causal role of higher BMI on higher stroke volume (difference per 3.58 kg/m 2 : 1.49 mL/m 2.04 ; 95% CI, 0.62–2.35; P =0.001) and cardiac output (difference per 3.58 kg/m 2 : 0.11 L·min -1 ·m -1.83 ; 95% CI, 0.03–0.19; P =0.01) but no strong evidence for a causal role on systemic vascular resistance or total arterial compliance. Neither analysis supported a causal role of higher BMI on heart rate. Conclusions: Complementary MR and RbG causal methodologies, together with a range of sensitivity analyses, suggest that higher BMI is likely to cause worse cardiovascular health, specifically higher blood pressure and left ventricular mass index, even in youth. Higher BMI also resulted in increased cardiac output in the RbG study, which appeared to be solely driven by stroke volume, as neither MR nor RbG analyses suggested a causal effect of BMI on heart rate. These consistent results support efforts to reduce BMI from a young age to prevent later adverse cardiovascular health and illustrate the potential for phenotypic resolution with maintained analytic power using RbG.
AB0908 ARE CHRONIC PAIN SYNDROMES BEHIND STATIN-ASSOCIATED MUSCLE PAIN?
Authors: Yarden Yavne, Rivka Sheinin, Rita Nogueira, Nicola Luigi Bragazzi, Shmuel Tiosano, Abdulla Watad, Kassem Sharif, Daniela Amital, Hofit Cohen, Howard Amital
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Statin myalgia, defined as muscle pain or weakness without elevation of CPK levels, is a common complaint among statin users. Chronic pain syndromes affect a high percentage of the population<sup>1</sup>, therefore it is likely that such syndromes may confound reports of statin myalgia. <h3>Objectives</h3> The objective of this study was to compare the occurence of chronic pain between patients taking statins who later developed myalgia with those who did not. <h3>Methods</h3> This study included 112 statin-treated patients at the Lipid Center in Tel Hashomer - 56 of whom were diagnosed with Statin Asocciated Muscle Symptoms [SAMS] and 56 patients who were not. Questionnaires were used to assess diagnoses of fibromyalgia, pain intensity, functional impairment, anxiety and depression in the study population. <h3>Results</h3> Patients with statin myalgia were more likely to fulfill the diagnostic criteria for fibromyalgia than patients without stating myalgia (11 vs. 0, respectively). Patients in the SAMS group also exhibited higher levels of anxiety and depression in comparison with the control group. Female sex, scoring in Brief Pain Inventory pain intensity, and a Hamilton level indicative of an anxiety disorder were found to be significant predictors for fibromyalgia in patients suffering from stating myalgia. <h3>Conclusion</h3> A significant percentage of patients who were thought to suffer from statin myalgia fulfill the criteria for fibromyalgia, depression or anxiety. Detection of these patients and treatment of their priamry pain or psychiatric illness may prevent cessation of effective statin therapy. <h3>Reference</h3> [1] Cho L, Rocco M, Colquhoun D, et al. Clinical Profile of Statin Intolerance in the Phase 3 GAUSS-2 Study. Cardiovasc Drugs Ther2016;30(3):297–304. <h3>Disclosure of Interests</h3> Yarden Yavne: None declared, Rivka Sheinin: None declared, Rita Nogueira: None declared, Nicola Luigi Bragazzi: None declared, Shmuel Tiosano: None declared, Abdulla Watad: None declared, Kassem Sharif: None declared, Daniela Amital: None declared, Hofit Cohen: None declared, Howard Amital Grant/research support from: Pfizer, AbbVie, Janssen, Grant/research support from: Pfizer, AbbVie, Janssen, Consultant for: Pfizer, Merck Sharp &amp; Dohme, Consultant for: Pfizer, Merck Sharp &amp; Dohme, Speakers bureau: Pfizer, Merck Sharp &amp; Dohme, Janssen, Sanofi, Bristol-Myers Squibb, Abbvie, Neopharm, Speakers bureau: Pfizer, Merck Sharp &amp; Dohme, Janssen, Sanofi, Bristol-Myers Squibb, Abbvie, Neopharm
Concerning Greater Social Contexts in Bariatric Surgery Availability and Telomere Length Outcomes—Reply
Authors: John Morton, Trit Garg, Natalia Leva
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
AB0200 INHIBITION OF DOT1L ACTIVITY IN HUMAN SKIN FIBROBLASTS: A TRANSCRIPTOME ANALYSIS
Authors: Nathalie Berghen, Ellen De Langhe, Rik Lories
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The pathophysiology of fibrosis, a hallmark of diseases like Systemic Sclerosis, is still not well understood. The role of epigenetic factors is increasingly explored. DOT1L, the unique H3K79-methyltransferase, methylates histone 3 at the Lysine residue at position 79, thereby regulating gene expression programs. Inhibition of DOT1L in cartilage and bone has cell-type specific effects on Wnt signaling, a pathway suggested to play an important role in fibrotic disease. <h3>Objectives</h3> To study the changes in the transcriptome of dermal fibroblasts after DOT1L inhibition. <h3>Methods</h3> Primary human dermal fibroblasts isolated from abdominal skin were treated with DOT1L-inhibitor EPZ-5676 or vehicle and stimulated or not with TGF-β or CHIR99021 (activating Wnt signaling). RNAseq was performed using the NextSeq500 as a platform and TruSeq as library prep kit. The preprocessed reads were aligned to the reference genome of Homo-sapiens (Ensembl.GRCh38.88(GRCh38)). Statistical comparative analysis for differential expressed genes (DEG) was done using the edge package in R version 3.20.9. The resulting p-values were corrected for multiple testing with Benjamini-Hochberg to control for false discovery rate (FDR). DEG were selected based on FDR-value less than 0.05 and a fold change of an absolute log<sub>2</sub>-ratio larger than 1. Pathway analysis was done using PANTHER14.0. Western Blot for di-methylated H3K79 was performed to confirm successful DOT1L inhibition. <h3>Results</h3> The DOT1L-inhibitor EPZ-5676 effectively reduced H3K79 di-methylation in the treated samples. RNAseq analysis revealed 663 differentially expressed genes in dermal fibroblasts exposed to the DOT1L inhibitor, based on group analysis: 77 genes were downregulated and 556 upregulated. There was no significant interaction between inhibition of DOT1L and stimulation&lt;/span&gt; of the cells with TGF-β or CHIR99021. Pathway analysis showed involvement of primarily the integrin signaling, the cadherin pathway and Wnt signaling. <h3>Conclusion</h3> More than 600 differentially expressed genes were discovered by RNA sequencing in human dermal fibroblasts exposed to DOT1L inhibition (independent of TGF-β or CHIR 99021 stimulation). These gene lists and their networks indicate that DOT1L activity affects integrin signaling, the cadherin and Wnt pathway, suggesting a potential impact on the fibrotic process that is leading to pathology in SSc. <h3>Acknowledgement</h3> RNA sequencing and analysis was performed by VIB Nucleomics Core (www.nucleomics.be). <h3>Disclosure of Interests</h3> Nathalie Berghen: None declared, Ellen De Langhe: None declared, Rik Lories Consultant for: Abbvie, Celgene, Eli-Lilly, Janssen, Merck, Novartis, Pfizer, UCB
Evolution of local mutation rate and its determinants
Authors: Nadezhda V. Terekhanova, Vladimir B. Seplyarskiy, Ruslan A. Soldatov, Georgii A. Bazykin
Journal: Molecular Biology and Evolution (2017)

Mutation rate varies along the human genome, and part of this variation is explainable by measurable local properties of the DNA molecule. Moreover, mutation rates differ between orthologous genomic regions of different species, but the drivers of this change are unclear. Here, we use data on human divergence from chimpanzee, human rare polymorphism, and human de novo mutations to predict the substitution rate at orthologous regions of non-human mammals. We show that the local mutation rates are very similar between human and apes, implying that their variation has a strong underlying cryptic component not explainable by the known genomic features. Mutation rates become progressively less similar in more distant species, and these changes are partially explainable by changes in the local genomic features of orthologous regions, most importantly, in the recombination rate. However, they are much more rapid, implying that the cryptic component underlying the mutation rate is more ephemeral than the known genomic features. These findings shed light on the determinants of mutation rate evolution.local mutation rate, molecular evolution, recombination rate.
Abstract 16675: STIM2-mediated Increase in the Resting [Ca2+]cyt Contributes to Enhancing Pulmonary Arterial Smooth Muscle Cell Proliferation in Patients With Pulmonary Arterial Hypertension
Authors: Shanshan Song, Shane Carr, Kimberly M McDermott, Marisela Rodriguez, Angela Balistrieri, Ramon J Ayon, Ayako Makino, Jason X Yuan
Journal: Circulation (2017)

A rise in cytosolic [Ca2+] ([Ca2+]cyt) in pulmonary arterial smooth muscle cells (PASMCs) triggers pulmonary vasoconstriction and stimulates PASMCs proliferation leading to pulmonary arterial wall ...
Skmer: assembly-free and alignment-free sample identification using genome skims
Authors: Shahab Sarmashghi, Kristine Bohmann, M. Thomas P. Gilbert, Vineet Bafna, Siavash Mirarab
Journal: Genome biology (2019)

The ability to inexpensively describe taxonomic diversity is critical in this era of rapid climate and biodiversity changes. The recent genome-skimming approach extends current barcoding practices beyond short markers by applying low-pass sequencing and recovering whole organelle genomes computationally. This approach discards the nuclear DNA, which constitutes the vast majority of the data. In contrast, we suggest using all unassembled reads. We introduce an assembly-free and alignment-free tool, Skmer, to compute genomic distances between the query and reference genome skims. Skmer shows excellent accuracy in estimating distances and identifying the closest match in reference datasets.
AB0416C THE RESULTS OF THE USE OF TOFACITINIB (TOFA) IN PATIENTS WITH RHEUMATOID ARTHRITIS (RA) IN MOSCOW. ANALYSIS DATA FROM MOSCOW UNIFIED ARTHRITIS REGISTRY(MUAR)
Authors: Evgeniya Shmidt, Ekaterina Koltsova, Galina Lukina, Karine Lytkina, Evgeniy Zhilyaev
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Moscow Unified Arthritis Registry (MUAR) started at 01 DEC 2012. By 01 DEC 2017, 829 RA patients were included in the register. <h3>Objectives</h3> The aim of the study was to evaluate the effectiveness and treatment survival of TOFA and identify predictors of the effectiveness of TOFA. <h3>Methods</h3> The inclusion criteria were diagnosis of RA, established at any time according to ACR (1987) or ACR/EULAR (2010) criteria; persons receiving or planning to receive targeted therapy for RA; signed informed consent to participate in the study. All episodes of treatment with TOFA in which there was at least 1 visit not earlier than 6 months since the start of the drug were included for efficacy analysis. <h3>Results</h3> Data of 48 patients treated with TOFA were extracted from the registry. Women were 41 (85,4%), mean age was 55,1 ± 12,4 years; age at the disease beginning was 44,3 ± 14,0; 6 (12,5%) of patients were smokers; mean time on TOFA was 552 ± 259 days. One of the independent predictors of achieved DAS28 was sex - 0.49 lower in men (p&lt;0.001). There was no correlation of achieved disease activity with number of previous failures with biologics. Patients seropositive for rheumatoid factor achieved significantly lower activity (p =0,015). There was also a trend towards lower achieved activity in patients with rheumatoid nodules (p = 0,059). On the first line of targeted treatment, survival of TOFA was significantly better than Infliximab, Adalimumab and Certolizumab pegol. On the second line – better than Infliximab. On the following lines TOFA was better than Adalimumab, but worse than Etanercept. Due to the fact that most of treatment episodes with TOFA are not completed, the average duration of treatment may be underestimated. There was no significant decrement of retention on therapy after multiple treatment failures (tab.). <b>Conclusion:</b> The effectiveness and treatment survival of TOFA does not depend on the number of previous failures with biologics; the best results of TOFA can be expected in men and seropositive patients; the presence of rheumatoid nodules can be considered as a special indication for TOFA. <h3>Disclosure of Interests</h3> None declared
AB1383-HPR THE VALIDITY AND RELIABILITY OF UNSUPPORTED UPPER LIMB EXERCISE TEST IN INDIVIDUALS WITH RHEUMATOID ARTHRITIS
Authors: S. Yaprak Cetin, Bilge Basakci Calik, Ayse Ayan, Ugur Cavlak
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Rheumatoid arthritis (RA) is a systemic, inflammatory disease that causes pain, joint destruction and disability. RA affects the function of the hand and upper extremities; function deteriorates as the disease progresses and affects independence. Unsupported upper-limb exercise (UULEX) test was developed to evaluate upper extremity function and endurance in individuals with Chronic Obstructive Pulmonery Disease. It is suggested that this test can be used in other clinical cases with arm disabilities. <h3>Objectives</h3> The aim of this study was to examine whether the UULEX Test is valid and reliable in individuals with RA. <h3>Methods</h3> 71 individuals with RA (15 male, 56 female) with an average age of 52.15 10.11 were included in the study. The Intraclass Correlation Coefficient (ICC) was used to assess the reliability of the UULEX test. Each individual was assessed by one physiotherapists in two different sessions, a week apart. The correlations of the UULEX test with Disabilities Arm, Shoulder and Hand (DASH), Health Assessment Questionnare (HAQ), 30 sec Push Up Test and 6 Peg Board Ring Test were assessed for concurrent validity. <h3>Results</h3> Intrarater reliability of final level, final weight, duration of the UULEX Test were determined to be excellent (ICC= 0.922, 0.960, 0.958). A moderate to excellent correlation was found between UULEX Test and DASH, HAQ, 30 sec Push Up Test and 6 Peg Board Ring Test (p&lt;0.05). <h3>Conclusion</h3> The results of this study showed that the UULEX test is a valid and reliable method in the assessment of upper extremity endurance in individuals with RA. <h3>References</h3> [1] - Manning VL, Hurley MV, Scott DL, Coker B, Choy E. Bearne LM. Education, Self-Management, and Upper Extremity Exercise Training in People With Rheumatoid Arthritis: A Randomized Controlled Trial. Arthritis Care &amp; Research 2014; 66, 2: 217227. [2] - Hammond A, Prior Y, Tyson S. Linguistic validation, validity and reliability of the British English versions of the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and QuickDASH in people with rheumatoid arthritis BMC Musculoskeletal Disorders 2018; 19:118 [3] - Lima VP, Velloso M, Almeida FD, Carmona B, Ribeiro-Samora GA, Ferreira TJ. Testretest reliability of the unsupported upperlimb exercise test (UULEX) and 6-min peg board ring test (6PBRT) in healthy adult individuals.Physiotherapy Theory and Practice 2018; 34, 10:806812 [4] - Takahashi T, Jenkins SC, Strauss GR, Watson CP, Lake FR. A New Unsupported Upper Limb Exercise Test for Patients With Chronic Obstructive Pulmonary Disease. Journal of Cardiopulmonary Rehabilitation 2003;23:430-437. <h3>Disclosure of Interests</h3> None declared
Post-mortem molecular profiling of three psychiatric disorders
Authors: Ryne C. Ramaker, Kevin M. Bowling, Brittany N. Lasseigne, Megan H. Hagenauer, Andrew A. Hardigan, Nicholas S. Davis, Jason Gertz, Preston M. Cartagena, David M. Walsh, Marquis P. Vawter, Edward G. Jones, Alan F. Schatzberg, Jack D. Barchas, Stanley J. Watson, Blynn G. Bunney, Huda Akil, William E. Bunney, Jun Z. Li, Sara J. Cooper, Richard M. Myers
Journal: Genome Medicine (2017)

Psychiatric disorders are multigenic diseases with complex etiology that contribute significantly to human morbidity and mortality. Although clinically distinct, several disorders share many symptoms, suggesting common underlying molecular changes exist that may implicate important regulators of pathogenesis and provide new therapeutic targets. We performed RNA sequencing on tissue from the anterior cingulate cortex, dorsolateral prefrontal cortex, and nucleus accumbens from three groups of 24 patients each diagnosed with schizophrenia, bipolar disorder, or major depressive disorder, and from 24 control subjects. We identified differentially expressed genes and validated the results in an independent cohort. Anterior cingulate cortex samples were also subjected to metabolomic analysis. ChIP-seq data were used to characterize binding of the transcription factor EGR1. We compared molecular signatures across the three brain regions and disorders in the transcriptomes of post-mortem human brain samples. The most significant disease-related differences were in the anterior cingulate cortex of schizophrenia samples compared to controls. Transcriptional changes were assessed in an independent cohort, revealing the transcription factor EGR1 as significantly down-regulated in both cohorts and as a potential regulator of broader transcription changes observed in schizophrenia patients. Additionally, broad down-regulation of genes specific to neurons and concordant up-regulation of genes specific to astrocytes was observed in schizophrenia and bipolar disorder patients relative to controls. Metabolomic profiling identified disruption of GABA levels in schizophrenia patients. We provide a comprehensive post-mortem transcriptome profile of three psychiatric disorders across three brain regions. We highlight a high-confidence set of independently validated genes differentially expressed between schizophrenia and control patients in the anterior cingulate cortex and integrate transcriptional changes with untargeted metabolite profiling.