tbuckley/cabot-search huggingface dataset:
08.06 Circulating exosomes play a role in the regulation of human in vitro osteoclastogenesis
Authors: Nikolett Marton, Orsolya Tunde Kovacs, Eszter Baricza, Agnes Kittel, David Gyori, Attila Mocsai, Florian Meier, Carl S Goodyear, Iain B McInnes, Edit I Buzas, Gyorgy Nagy
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> Exosomes (EXOs) belong to the subcellular sized signalosomes called extracellular vesicles (EVs). EVs, which are present in blood and other bodily fluids, carry a broad spectrum of biomolecules that can influence cellular function. It is conceivable that the vesicle composition of EVs is altered in inflammatory diseases, and that this could contribute to disease pathogenesis. Bone tissue is the second biggest consumer of circulating EVs, but the effect of blood derived EXOs on bone homeostasis has not been described before. Our aim was to study the possible role of circulating EVs on the human <i>in vitro</i> osteoclastogenesis in healthy individuals and in those with active arthritis. <h3>Methods</h3> Blood samples of healthy volunteers, rheumatoid arthritis (RA, DAS: 4.79±1.96) according to the 2010 ACR/EULAR classification criteria and psoriatic arthritis (PsA, DAS: 2.79±0.72) patients with peripheral arthritis according to the classification criteria for psoriatic arthritis were collected. EXOs were isolated by gravity filtration and ultracentrifugation. To investigate the properties of EXO samples resistive pulse sensing technique, transmission electron microscopy, and western blot were performed. CD14+ cells were separated from PBMCs with positive selection <i>(StemCell)</i>, and the cells were stimulated with 50 ng/ml recombinant human M-CSF, RANKL <i>(PeproTech)</i> and blood-derived EXOs. After 7 days, the cells were fixed and stained for tartrate resistant acid phosphatase (TRAP) <i>(Sigma)</i> and the TRAP positive multinucleated cells were counted. Student's t test and one–way ANOVA with Tukey post hoc test were used as statistical analysis. <h3>Results</h3> EXO characterisation revealed the expression of classical exosome markers (i.e., CD9, CD63, flotilin-1, TSG-101) and an average diameter of 100 nm. Healthy (n=11) and RA derived (n=12) EXOs profoundly inhibited osteoclast differentiation (p&lt;0.01), by contrast the PsA derived (n=10) EXOs had a stimulatory effect (p&lt;0.05). In cross-treatment experiments where EXOs and CD14+ cells were interchanged between the 3 groups, healthy (n=5) and RA (n=5) derived EXOs inhibited (p&lt;0.01) the generation of osteoclasts in all groups, while the PsA (n=7) derived EXOs did not have an inhibitory effect. <h3>Conclusions</h3> Our abovementioned data suggest that, in a disease-specific manner, circulating EXOs are novel regulators of the human osteoclastogenesis.
膀胱癌に対する光線力学的診断と三種併用治療のための新しいセラノスティックnanoporphyrins【Powered by NICT】
Authors: Lin Tzu-Yin, Li Yuanpei, Liu Qiangqiang, Chen Jui-Lin, Zhang Hongyong, Lac Diana, Zhang Hua, W Ferrara Katherine, Wachsmann-Hogiu Sebastian, Li Tianhong, Airhart Susan, deVere White Ralph, S Lam Kit, Pan Chong-Xian
Journal: Biomaterials (2016)
食用ショウガderivedナノ粒子:炎症性腸疾患および大腸炎関連癌の予防と治療のための新規治療アプローチ【Powered by NICT】
Authors: Zhang Mingzhen, Viennois Emilie, Prasad Meena, Zhang Yunchen, Wang Lixin, Zhang Zhan, Han Moon Kwon, Xiao Bo, Xu Changlong, Srinivasan Shanthi, Merlin Didier
Journal: Biomaterials (2016)
Ineffective Policies to Address the Opioid Epidemic—Reply
Authors: Bertha K. Madras
Journal: JAMA Psychiatry (2017)

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 Psychiatry 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 Psychiatry journal
OP0174 New protein array technology identifies rituximab treated non responder rheumatoid arthritis patients are generating a new autoantibody repertoire
Authors: Z Konthur, M Wiemkes, T Häupl, G Burmester, K Skriner
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> Rituximab (RTX) has shown clinical efficacy but up to 40% of RTX treated rheumatoid arthritis (RA) patients are poor responders (Ann-Rheum-Dis. 2005 Feb;64(2):246–52) and the commonly used RA biomarkers (<i>RF/ACPA)</i> are poor predictors for therapy response. In this study the autoantibody repertoire analysed on protein macorarrays from RA patients under RTX treatment was correlated to clinical DAS28 response. <h3>Methods</h3> Screening of RA sera was conducted on 37.830 unique human proteins on protein marcoarrays (http://www.engine-gmbh.de)with sera taken before and 24 weeks after treatment. The autoantibody response of different immunoglobulin classes IgD, IgA, and IgG was recorded and bioinformatically evaluated. Response was determined according to DAS28 criteria. DAS 28 scores in the responder group before treatment was from 5.4 – 7.8 and in the non-responder group 5,6 – 6,8. We analyzed 26 RA patient sera (9 responder, 7 non-responder and 10 patients with blinded response classification) investigated the data of found autoantigens <i>in-silico</i> and by hierarchical clustering <h3>Results</h3> In the cohort of 26 patients 1292 different autoantigens (IgD,IgA,IgG) were detected. Using protein array we investigated clusters of autoantigen responses that disappeared or developed during RTX treatment of RA patients. RA autoantigenic patterns before and 6 month after RTX treatment were patient-specific and no relevant autoantigenic cluster was found that was shared between patients or associated with response. However, RTX reduced the repertoire of autoantibodies after 24 weeks of treatment in the tested RA patient cohort on average by 60%. RA patients which do not respond are generating on average 63% new autoantibodies. In good responders to RTX only 5,5% (+/-3%) new autoantibodies can be detected. The IgA and IgG autoantibody repertoire in the serum after 24 weeks of RTX treatment is reduced (IgA: 41%, IgG: 31%) in good responders whereas it is increased (IgA: 1,3%, IgG: 24%) in non responders to RTX. <h3>Conclusions</h3> After 6 month of RTX treatment the autoantibody repertoire in all good responding RA patients is reduced and non responders to RTX change their autoantibody repertoire directed against new but patient specific antigens. The fast rebuilding of functional B cells is only detected in non-responders to rituximab. <h3>Disclosure of Interest</h3> None declared
IMPACT OF A COMPREHENSIVE FIFA 11+ WORKSHOP ON YOUTH SOCCER COACHES' TASK SELF-EFFICACY FOR PROGRAM IMPLEMENTATION
Authors: Oluwatoyosi Owoeye, Muge Bulat, Carly McKay, Tate Hubka, Luz Palacios-Derflingher, Kathryn Schneider, Carolyn Emery
Journal: British Journal of Sports Medicine (2017)

Background Coach-led delivery of the FIFA 11+ warm-up program is an effective strategy for program implementation. There is emerging evidence that coaches' task self-efficacy (TSE) predicts FIFA 11+ implementation in youth soccer. Objective To determine the impact of a comprehensive FIFA 11+ workshop on youth soccer coaches' TSE. Design Quasi-experimental pilot study. Setting Community youth soccer. Participants This study involved 73 Canadian coaches (66.7% male, aged 18–66 years) participating in a pilot pre-implementation FIFA 11+ workshop (Spring 2016). Interventions Experts with experience in program implementation delivered a coach workshop, comprising an extensive theory-based classroom session and a field-based practical demonstration of the FIFA 11+ program. Main Outcome Measurements A questionnaire was used to assess coaches' TSE for implementing the FIFA 11+ on a 7-point Likert scale. Difference in the pre-post workshop ratings of TSE as measured by coaches' confidence in both their understanding the FIFA 11+ program (TSE1) and their ability to use the program with their teams (TSE2). Wilcoxon matched-pairs signed-ranks test analysis was used to assess any statistical differences between baseline and post-workshop ratings of TSE. Results Coaches had a median (1st, 3rd quartiles) baseline TSE1 rating of 6 (4, 6) and TSE2 rating of 6 (5, 6). There were statistical significant differences in coaches' TSE1 (z=−3.99; p&lt;0.001) and TSE2 (z=−2.48; p=0.013) following workshop participation as compared to baseline. Conclusions A comprehensive FIFA 11+ workshop generated positive increases in coach TSE, which may help optimize program uptake and implementation. Further evaluation of this coach workshop strategy on behavioural and implementation outcomes will be performed in a large population of coaches across different cities in Canada in an ongoing nationwide implementation of the FIFA 11+ program in youth soccer.
Effect of Intensive Versus Standard Blood Pressure Treatment According to Baseline Prediabetes Status: A Post Hoc Analysis of a Randomized Trial
Authors: Adam P. Bress, Jordan B. King, Kathryn E. Kreider, Srinivasan Beddhu, Debra L. Simmons, Alfred K. Cheung, Yingying Zhang, Michael Doumas, John Nord, Mary Ellen Sweeney, Addison A. Taylor, Charles Herring, William J. Kostis, James Powell, Anjay Rastogi, Christianne L. Roumie, Alan Wiggers, Jonathan S. Williams, Reem Yunis, Athena Zias, Greg W. Evans, Tom Greene, Michael V. Rocco, William C. Cushman, David M. Reboussin, Mark N. Feinglos, Vasilios Papademetriou
Journal: Diabetes Care (2017)

OBJECTIVE To determine whether the effects of intensive (&amp;lt;120 mmHg) compared with standard (&amp;lt;140 mmHg) systolic blood pressure (SBP) treatment are different among those with prediabetes versus those with fasting normoglycemia at baseline in the Systolic Blood Pressure Intervention Trial (SPRINT). RESEARCH DESIGN AND METHODS This was a post hoc analysis of SPRINT. SPRINT participants were categorized by prediabetes status, defined as baseline fasting serum glucose ≥100 mg/dL versus those with normoglycemia (fasting serum glucose &amp;lt;100 mg/dL). The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment among those with prediabetes and normoglycemia. RESULTS Among 9,361 participants randomized (age 67.9 ± 9.4 years; 35.5% female), 3,898 and 5,425 had baseline prediabetes and normoglycemia, respectively. After a median follow-up of 3.26 years, the hazard ratio for the primary outcome was 0.69 (95% CI 0.53, 0.89) and 0.83 (95% CI 0.66, 1.03) among those with prediabetes and normoglycemia, respectively (P value for interaction 0.30). For all-cause mortality, the hazard ratio with intensive SBP treatment was 0.77 (95% CI 0.55, 1.06) for prediabetes and 0.71 (95% CI 0.54, 0.94) for normoglycemia (P value for interaction 0.74). Effects of intensive versus standard SBP treatment on prespecified renal outcomes and serious adverse events were similar for prediabetes and normoglycemia (all interaction P &amp;gt; 0.05). CONCLUSIONS In SPRINT, the beneficial effects of intensive SBP treatment were similar among those with prediabetes and fasting normoglycemia.
Convergent roles of ATF3 and CSL in chromatin control of cancer-associated fibroblast activation
Authors: Dong Eun Kim, Maria-Giuseppina Procopio, Soumitra Ghosh, Seung-Hee Jo, Sandro Goruppi, Francesco Magliozzi, Pino Bordignon, Victor Neel, Paolo Angelino, G. Paolo Dotto
Journal: The Journal of Experimental Medicine (2017)

Cancer-associated fibroblasts (CAFs) are important for tumor initiation and promotion. CSL, a transcriptional repressor and Notch mediator, suppresses CAF activation. Like CSL, ATF3, a stress-responsive transcriptional repressor, is down-modulated in skin cancer stromal cells, and Atf3 knockout mice develop aggressive chemically induced skin tumors with enhanced CAF activation. Even at low basal levels, ATF3 converges with CSL in global chromatin control, binding to few genomic sites at a large distance from target genes. Consistent with this mode of regulation, deletion of one such site 2 Mb upstream of IL6 induces expression of the gene. Observed changes are of translational significance, as bromodomain and extra-terminal (BET) inhibitors, unlinking activated chromatin from basic transcription, counteract the effects of ATF3 or CSL loss on global gene expression and suppress CAF tumor-promoting properties in an in vivo model of squamous cancer-stromal cell expansion. Thus, ATF3 converges with CSL in negative control of CAF activation with epigenetic changes amenable to cancer- and stroma-focused intervention.
Assessing risk in pulmonary arterial hypertension: what we know, what we don't
Authors: Raymond L. Benza, Harrison W. Farber, Mona Selej, Mardi Gomberg-Maitland
Journal: European Respiratory Journal (2017)

Despite improvement in short-term survival, pulmonary arterial hypertension (PAH) remains an incurable disease with an unacceptable median survival of 7 years [1]. In the USA, the survival rates for PAH patients awaiting transplant continue to mirror the 2.5-year survival rate in the pretreatment era of the disease [2]. Despite treatment, PAH patients continue to experience disease progression and increased rates of hospitalisations due to right heart failure. Importantly, right heart failure hospitalisations in PAH occur at rates that are comparable to patients with left heart disease, particularly in those aged greater than 65 [3] More so, morbid events in PAH, notably hospitalisations, herald disease progression and early mortality [4, 5]. Hence, along with advancing PAH treatment options, appropriate and accurate risk prediction is essential to halt disease progression and make individualised treatment decisions. Risk stratification in PAH is best served by joint use of the ERS/ESC risk table and REVEAL calculator risk tools <http://ow.ly/ySrB30dKq9r>
Targeted MAPK Pathway Inhibitors in Patients With Disseminated Pilocytic Astrocytomas
Authors: Anastasia Drobysheva, Laura J. Klesse, Daniel C. Bowers, Veena Rajaram, Dinesh Rakheja, Charles F. Timmons, Jason Wang, Korgun Koral, Lynn Gargan, Erica Ramos, Jason Y. Park
Journal: Journal of the National Comprehensive Cancer Network (2017)

This report presents a series of 5 pediatric patients with disseminated pilocytic astrocytomas and frequent nonfusion activating mutations. Genetic variants in these patients' tumors include BRAF p.Val600Glu, BRAF p.Val600Asp, and KRAS p.Gly60_Gln62ins7. The 2 patients with BRAF-mutated tumors were treated with dabrafenib or a combination of dabrafenib plus trametinib. The patients had either near complete resolution of the primary tumor (BRAF p.Val600Glu) or a stable primary tumor (BRAF p.Val600Asp). Both patients showed improvement in leptomeningeal dissemination without significant toxicity. Genomic testing of disseminated pilocytic astrocytomas, particularly those arising at extracerebellar locations, may result in the identification of mutations associated with ERK/MAPK activation. Patients with these activating mutations may benefit from targeted therapies.
SAT0706 End-stage organ failure in sarcoidosis: characterization and predictive factors in 1082 patients
Authors: R Pérez-Alvarez, B Kostov, A García González, R Gόmez De La Torre, M Lopez Dupla, B De Escalante, A Alguacil, J Chara, J Velilla, J Rascόn, JS Garcia Morillo, C Feijoo, E Fonseca, M Bonet, JL Callejas, G de la Red, AB Madroñero Vuelta, C Soler, E Peral, JF Gόmez Cerezo, G Cruz, P Perez, S Fernández Rodríguez, B Pinilla, A Gato, M Akasbi, A Robles, I Ojeda, MJ Vives, C Morcillo, M Penadés, M De Vicente, M Ramos-Casals, L Pallarés, P Brito-Zerόn
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To characterize the main features at presentation of sarcoidosis associated with the development of end-stage organ failure in a large multicenter cohort of patients from Southern Europe. <h3>Methods</h3> In January 2017, the Spanish National Registry of Sarcoidosis (SARCOGEAS-SEMI) included 1082 consecutive patients diagnosed with sarcoidosis according to the ATS/ERS/WASOG 1999 statement and extrathoracic involvement to the 2014 WASOG instrument. The development of end-stage organ failure was assessed at the last visit. <h3>Results</h3> The cohort consisted of 618 (57%) women and 464 (43%) men, with a mean age at diagnosis of 47yrs. After a mean follow-up of 82 months, 90 (8%) patients developed end-stage organ failure, including respiratory failure (n=56), chronic renal failure (n=13), cardiac failure/permanent cardiac device (n=8) and liver cirrhosis (n=3). The following baseline features were associated with end-stage organ failure in the univariate analysis: patients born in Spain (p=0.008), a higher mean age at diagnosis (p&lt;0.001) and a radiological stage III/IV (p&lt;0.001) With respect to extrathoracic involvement, spleen (p=0.015), renal (p=0.001), cardiac (p=0.028) and bone marrow (p=0.003) involvements, hypercalcemia (p=0.018) and use of corticosteroids (p&lt;0.001) were associated with end-stage organ failure, while patients with cutaneous sarcoidosis had a lower risk (p=0.029). Multivariate analysis identified age at diagnosis (OR 1.05), radiological stages III/IV (OR 3.12) and use of corticosteroids (OR 4.55) as independent variables associated with the development of end-stage organ failure. <h3>Conclusions</h3> Nearly 10% of patients with sarcoidosis developed end-stage organ failure. Respiratory failure represented two thirds of cases of sarcoidosis-related organ failure, followed by renal (15% of cases) and cardiac (9%). Older patients, as well as those presenting with advanced radiological stages, had an enhanced risk of developing end-stage organ failure. <h3>Disclosure of Interest</h3> None declared
MEASURES OF LIMB SYMMETRY USED FOR INJURY RISK IDENTIFICATION: WHAT IS NORMAL?
Authors: Scott Lawrance, Clyde Killian, Peter Rundquist, Walter Jenkins
Journal: British Journal of Sports Medicine (2017)

Background Limb asymmetries have been identified as a significant predictor of injury risk. However, the natural boundaries of variation in a non-injured population using clinically relevant and reliable measures has not been determined. Objective To assess clinical measures of limb symmetry and determine the natural boundaries of symmetry present in a non-injured population. Design Prospective cohort study. Setting Controlled laboratory research. Participants 39 non-injured participants, 12 male, 27 female (23.2±2.9 years, 170.2±9.1 cm, 68.4±15.6 kg). Assessment of Risk Factors Knee PROM, effusion, endfeel, knee extension, flexion, and hip abduction strength, dynamic balance, single leg hop, and IKDC Subjective rating were measured. Main Outcome Measurements In measures demonstrating excellent reliability (ICC≥0.75, Kappa≥0.81), limb symmetry index (LSI) and variability scores were calculated. Results All clinical measures, except hip abduction strength, demonstrated excellent reliability. Knee extension PROM was 6.0±5.0°, flexion PROM was 154.0±5.0°. 100% of participants had normal knee extension endfeel, and no knee effusion. 95% had normal flexion endfeel. LSI scores for each measure ranged between 96.6–100.0%. Using minimal detectable change (MDC) scores for each measure, boundaries of limb symmetry were calculated for knee extension PROM (100±1.0°), knee flexion PROM (100±4°), knee extension strength (100±21.0%), knee flexion strength (100±24.0%), dynamic balance (100±6.0%), single leg hop (100±9.1%), and IKDC Subjective rating (100±3.3%). Conclusions Most measures of limb symmetry used in the study demonstrated appropriate reliability for clinical use. Although strength measures had high degrees of limb symmetry, there was significant variability present in non-injured participants. Conversely, high levels of limb symmetry with very little variation were observed in knee PROM, dynamic balance, single leg hop, and IKDC Subjective measures. Strength may not be the best measure of limb symmetry while PROM, dynamic balance, single leg hop, and the IKDC Subjective form appear to have more utility to identify limb asymmetries.
Identification of Novel Breast Cancer Risk Loci
Authors: Claire Hian Tzer Chan, Prabhakaran Munusamy, Sau Yeen Loke, Geok Ling Koh, Edward Sern Yuen Wong, Hai Yang Law, Chui Sheun Yoon, Min-Han Tan, Yoon Sim Yap, Peter Ang, Ann Siew Gek Lee
Journal: Cancer Research (2017)

It has been estimated that >1,000 genetic loci have yet to be identified for breast cancer risk. Here we report the first study utilizing targeted next-generation sequencing to identify single-nucleotide polymorphisms (SNP) associated with breast cancer risk. Targeted sequencing of 283 genes was performed in 240 women with early-onset breast cancer (≤40 years) or a family history of breast and/or ovarian cancer. Common coding variants with minor allele frequencies (MAF) >1% that were identified were presumed initially to be SNPs, but further database inspections revealed variants had MAF of ≤1% in the general population. Through prioritization and stringent selection criteria, we selected 24 SNPs for further genotyping in 1,516 breast cancer cases and 1,189 noncancer controls. Overall, we identified the JAK2 SNP rs56118985 to be significantly associated with overall breast cancer risk. Subtype analysis performed for patient subgroups defined by ER, PR, and HER2 status suggested additional associations of the NOTCH3 SNP rs200504060 and the HIF1A SNP rs142179458 with breast cancer risk. In silico analysis indicated that coding amino acids encoded at these three SNP sites were conserved evolutionarily and associated with decreased protein stability, suggesting a likely impact on protein function. Our results offer proof of concept for identifying novel cancer risk loci from next-generation sequencing data, with iterative data analysis from targeted, whole-exome, or whole-genome sequencing a wellspring to identify new SNPs associated with cancer risk. Cancer Res; 77(19); 5428-37. ©2017 AACR.
3′エキソヌクレアーゼTOE1の両対立遺伝子性変異は,橋小脳低形成を引き起こし,TOE1のsnRNAプロセシングにおける役割を明らかにする
Authors: Lardelli Rea M, Schaffer Ashleigh E, Shaw Tim L, Bennett Eric J, Lykke‐Andersen Jens, Gleeson Joseph G, Schlachetzki Zinayida, Rosti Basak, Akizu Naiara, Scott Eric, Silhavy Jennifer L, Heckman Laura Dean, Rosti Rasim Ozgur, Dikoglu Esra, Gregor Anne, Guemez‐Gamboa Alicia, Musaev Damir, Mande Rohit, Widjaja Ari, Marin‐Valencia Isaac, Sathe Shashank, Van Nostrand Eric L, Markmiller Sebastian, Yeo Gene W, Eggens Veerle R C, Baas Frank, Zaki Maha S, Grainger Stephanie, Traver David, Davies Justin H, DE Meirleir Linda, Kayserili Hulya, Altunoglu Umut, Freckmann Mary Louise, Warwick Linda, Chitayat David, Blaser Susan, Caglayan Ahmet Okay, Gunel Murat, Bilguvar Kaya, Per Huseyin, Fagerberg Christina, Christesen Henrik T, Kibaek Maria, Aldinger Kimberly A, Dobyns William B, Manchester David, Matsumoto Naomichi, Saitsu Hirotomo, Muramatsu Kazuhiro, Shiina Masaaki, Ogata Kazuhiro, Foulds Nicola, Chi Neil C, Spaccini Luigina, Bova Stefania Maria, Gabriel Stacey B, Valente Enza Maria, Nassogne Marie‐Cecile
Journal: Nature Genetics (2017)