tbuckley/cabot-search huggingface dataset:
Midlife contributors to socioeconomic differences in frailty during later life: a prospective cohort study
Authors: Eric J Brunner, Martin J Shipley, Sara Ahmadi-Abhari, Carlos Valencia Hernandez, Jessica G Abell, Archana Singh-Manoux, Ichiro Kawachi, Mika Kivimaki
Journal: The Lancet Public Health (2018)

BackgroundHealth inequalities persist into old age. We aimed to investigate risk factors for socioeconomic differences in frailty that could potentially be modified through policy measures.MethodsIn this multi-wave longitudinal cohort study (Whitehall II study), we assessed participants' socioeconomic status, behavioural and biomedical risk factors, and disease status at age 45–55 years, and frailty (defined according to the Fried phenotype) at baseline and at one or more of three clinic visits about 18 years later (mean age 69 years [SD 5·9]). We used logistic mixed models to examine the associations between socioeconomic status and risk factors at age 50 years and subsequent prevalence of frailty (adjusted for sex, ethnic origin, and age), with sensitivity analyses and multiple imputation for missing data.FindingsBetween Sept 9, 2007, and Dec 8, 2016, 6233 middle-aged adults were measured for frailty. Frailty was present in 562 (3%) of 16 164 person-observations, and varied by socioeconomic status: 145 (2%) person-observations had high socioeconomic status, 241 (4%) had intermediate status, and 176 (7%) had low socioeconomic status, adjusting for sex and age. Risk factors for frailty included cardiovascular disease, depression, smoking, high or abstinent alcohol consumption, low fruit and vegetable consumption, physical inactivity, poor lung function, hypertension, and overweight or obesity. Cardiometabolic markers for future frailty were high ratio of total to high-density lipoprotein cholesterol, and raised interleukin-6 and C-reactive protein concentrations. The five most important factors contributing to the frailty gradient, assessed by percent attenuation of the association between socioeconomic status and frailty, were physical activity (13%), interleukin-6 (13%), body-mass index category (11%), C-reactive protein (11%), and poor lung function (10%). Overall, socioeconomic differences in frailty were reduced by 40% in the maximally-adjusted model compared with the minimally-adjusted model.InterpretationBehavioural and cardiometabolic risk factors in midlife account for more than a third of socioeconomic differences in frailty. Our findings suggest that interventions targeting physical activity, obesity, smoking, and low-grade inflammation in middle age might reduce socioeconomic differences in later-life frailty.FundingBritish Heart Foundation and British Medical Research Council.
Investigation of the Accuracy of 18 Marketed Blood Glucose Monitors
Authors: David C. Klonoff, Joan Lee Parkes, Boris P. Kovatchev, David Kerr, Wendy C. Bevier, Ronald L. Brazg, Mark Christiansen, Timothy S. Bailey, James H. Nichols, Michael A. Kohn
Journal: Diabetes Care (2018)

Cleared blood glucose monitors (BGMs) for personal use may not always deliver levels of accuracy currently specified by international and U.S. regulatory bodies. This study's objective was to assess the accuracy of 18 such systems cleared by the U.S. Food and Drug Administration representing approximately 90% of commercially available systems used from 2013 to 2015.A total of 1,035 subjects were recruited to have a capillary blood glucose (BG) level measured on six different systems and a reference capillary sample prepared for plasma testing at a reference laboratory. Products were obtained from consumer outlets and tested in three triple-blinded studies. Each of the three participating clinical sites tested a different set of six systems for each of the three studies in a round-robin. In each study, on average, a BGM was tested on 115 subjects. A compliant BG result was defined as within 15% of a reference plasma value (for BG ≥100 mg/dL [5.55 mmol/L]) or within 15 mg/dL (0.83 mmol/L) (for BG <100 mg/dL [5.55 mmol/L]). The proportion of compliant readings in each study was compared against a predetermined accuracy standard similar to, but more lenient than, current regulatory standards. Other metrics of accuracy included the overall compliance proportion; the proportion of extreme outlier readings differing from the reference value by >20%; modified Bland-Altman analysis including average bias, coefficient of variation, and 95% limits of agreement; and proportion of readings with no clinical risk as determined by the Surveillance Error Grid.The different accuracy metrics produced almost identical BGM rankings. Six of the 18 systems met the predetermined accuracy standard in all three studies, 5 systems met it in two studies, and 3 met it in one study. Four BGMs did not meet the accuracy standard in any of the three studies.Cleared BGMs do not always meet the level of analytical accuracy currently required for regulatory clearance. This information could assist patients, professionals, and payers in choosing products and regulators in evaluating postclearance performance.
TET1-Mediated Hypomethylation Activates Oncogenic Signaling in Triple-Negative Breast Cancer
Authors: Charly Ryan Good, Shoghag Panjarian, Andrew D. Kelly, Jozef Madzo, Bela Patel, Jaroslav Jelinek, Jean-Pierre J. Issa
Journal: Cancer Research (2018)

Abstract Both gains and losses of DNA methylation are common in cancer, but the factors controlling this balance of methylation remain unclear. Triple-negative breast cancer (TNBC), a subtype that does not overexpress hormone receptors or HER2/NEU, is one of the most hypomethylated cancers observed. Here, we discovered that the TET1 DNA demethylase is specifically overexpressed in about 40% of patients with TNBC, where it is associated with hypomethylation of up to 10% of queried CpG sites and a worse overall survival. Through bioinformatic analyses in both breast and ovarian cancer cell line panels, we uncovered an intricate network connecting TET1 to hypomethylation and activation of cancer-specific oncogenic pathways, including PI3K, EGFR, and PDGF. TET1 expression correlated with sensitivity to drugs targeting the PI3K–mTOR pathway, and CRISPR-mediated deletion of TET1 in two independent TNBC cell lines resulted in reduced expression of PI3K pathway genes, upregulation of immune response genes, and substantially reduced cellular proliferation, suggesting dependence of oncogenic pathways on TET1 overexpression. Our work establishes TET1 as a potential oncogene that contributes to aberrant hypomethylation in cancer and suggests that TET1 could serve as a druggable target for therapeutic intervention. Significance: This study addresses a critical gap in knowledge of how and why methylation is prognostic in breast cancer and shows how this information can be used to stratify patients with TNBC for targeted therapy. Cancer Res; 78(15); 4126–37. ©2018 AACR.
In COPD, long-term use of higher doses of inhaled corticosteroids was linked to increased fracture risk
Authors: Fergal J. O’Donoghue, Christine F. McDonald
Journal: Annals of Internal Medicine (2018)

ACP Journal Club19 June 2018In COPD, long-term use of higher doses of inhaled corticosteroids was linked to increased fracture riskFergal J. O’Donoghue, MB, BCh, PhD, FRACP, Christine F. McDonald, MBBS, PhD, FRACPFergal J. O’Donoghue, MB, BCh, PhD, FRACPInstitute for Breathing and Sleep and University of Melbourne, Melbourne, Victoria, Australia (F.J.O., C.F.M.)Search for more papers by this author, Christine F. McDonald, MBBS, PhD, FRACPInstitute for Breathing and Sleep and University of Melbourne, Melbourne, Victoria, Australia (F.J.O., C.F.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2018-168-12-071 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationGonzalez AV, Coulombe J, Ernst P, Suissa S. Long-term use of inhaled corticosteroids in COPD and the risk of fracture. Chest. 2018;153:321-8. https://pubmed.ncbi.nlm.nih.gov/28716642Clinical Impact RatingsGIM/FP/GP: Endocrinology: Geriatrics: Pulmonology: References1 Ferguson GT, Calverley PM, Anderson JA, et al. Prevalence and progression of osteoporosis in patients with COPD: results from the TOwards a Revolution in COPD Health study. Chest. 2009;136:1456-65. [PMID: 19581353] Google Scholar2 Johnell O, Pauwels R, Löfdahl CG, al. Bone mineral density in patients with chronic obstructive pulmonary disease treated with budesonide Turbuhaler. Eur Respir J. 2002;19:1058-63. [PMID: 12108857] Google Scholar3 Loke YK, Cavallazzi R, Singh S. Risk of fractures with inhaled corticosteroids in COPD: systematic review and meta-analysis of randomised controlled trials and observational studies. Thorax. 2011;66:699-708. [PMID: 21602540] Google Scholar4 Chalmers JD, Tebboth A, Gayle A, Ternouth A, Ramscar N. Determinants of initial inhaled corticosteroid use in patients with GOLD A/B COPD: a retrospective study of UK general practice. NPJ Prim Care Respir Med. 2017;27:43. [PMID: 28663549] Google Scholar5 Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease (2017 report). www.goldcopd.org/gold-2017-global-strategy-diagnosis-management-prevention-copd/ (accessed 25 Apr 2018). Google Scholar Author, Article, and Disclosure InformationAffiliations: Institute for Breathing and Sleep and University of Melbourne, Melbourne, Victoria, Australia (F.J.O., C.F.M.)This article was published at Annals.org on 5 June 2018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 June 2018Volume 168, Issue 12Page: JC71KeywordsAsthmaChronic obstructive pulmonary diseaseDatabasesDrug regulationDrugsHipMedical risk factorsOsteoporosisPulmonary medicineThorax ePublished: 19 June 2018 Issue Published: 19 June 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
AB0218 High level of cartilaginous oligomeric matrix protein is associated with the radiographic progression in patients with early rheumatoid arthritis
Authors: D. Rekalov, D. Nikitina
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Recent achievements have established that the very first years since the development of the RA are decisive in terms of the progression of the pathological process and the prediction of its remote consequences. This substantiated the need to reflect the heterogeneity and stage of the RA. First of all it concerns the early RA – a time point when the pathological process is in the primary exudative phase and its reversibility is significantly higher, because of not completely formed autoimmune mechanisms and the absence of pannus. <h3>Objectives</h3> Our aim was to establish the relationship between the levels of Anti-Citrullinated Peptide Antibody (ACPA), cartilaginous oligomeric matrix protein (COMP) and radiographic progression in patients with early RA <h3>Methods</h3> 75 patients with a diagnosis of early RA were examined, the duration of symptoms was less than 1 year (on average – 4.91±2.90 month) that were observed repeatedly on average after 12 months (11.8±1.2 months). The average age of patients was 46.4 years (from 34 to 62 years), 69.33% of the examined ones were women, the average duration of the disease at the time of the initial study was 107 days (57–194 days). Immune dysregulation in early RA was confirmed with the evaluation of the key proinflammatory cytokines – ACPA and COMP by the enzyme-linked immunosorbent assay (ELISA) according to the instructions for diagnostic kits. For the testing of articular cartilage lesions and injury of flexor's and extensor's tendons, MRI (1.5 T) and ultrasound diagnostics (US) were performed <h3>Results</h3> Immunological analysis of serum samples of ACPA, COMP was shown the role of these cytokines as prognostic factors of development and prognosis of early RA. The serological features of the obtained data revealed a correlation between the increased concentration of COMP and the progression of joint lesions without ACPA level increase. According to the baseline US data, the tendons of general flexor muscles and extensor brushes were most commonly observed in the examined patients: in general, 52 patients (69.3%) and 23 (30.7%), respectively. The injury of the tendons of individual fingers (I-V) in the mode of longitudinal and transverse scanning had its own patterns (table 1). <h3>Conclusions</h3> In patients with seronegative (normal ACPA ranges) early RA and high levels of COMP – the highest frequency of erosive and destructive changes can be observed. Injury of the tendons of flexors and extensors determined in major part of the patients with early RA. <h3>References</h3> [1] Alasaarela E, et al. Evaluation of humoral head erosions in RA: a comparison of US MRI, CT and plain radiography. Br J Rheumatol1998;37:1152–6. [2] Bang H, et al. Mutation and citrullination modifies vimentin to a novel autoantigen for RA. Arthritis Rheum2007;56:2503–2511. <h3>Disclosure of Interest</h3> None declared
Simultaneous side-by-side bilateral metal stent placement using a colonoscope in a patient with Billroth II reconstruction
Authors: Yasuki Hori, Itaru Naitoh, Katsuyuki Miyabe, Michihiro Yoshida, Akihisa Kato, Naruomi Jinno, Kazuki Hayashi
Journal: Endoscopy (2018)

Bilateral metal stent placement for malignant hilar biliary obstruction (MHBO) can be technically challenging, despite the frequent use of self-expandable metal stents (SEMSs) for palliative therapy [1] [2]. Simultaneous side-by-side (SBS) stent placement using a thin delivery system is straightforward and has a high success rate [3]. However, simultaneous SBS placement is considered to be technically difficult in patients with surgically altered anatomy because few suitable devices are available. This is the first report of simultaneous SBS stent placement for MHBO using a novel SEMS with a thin delivery system (Zeo Stent V; Zeon Medical, Tokyo, Japan) ([Fig. 1]) and a colonoscope in a patient with surgically altered anatomy.
SP0161 2018 eular recommendations for the management of hand osteoarthritis
Authors: M. Kloppenburg
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Hand osteoarthritis is a prevalent osteoarthritis phenotype, with high disease burden. With regard to the management of patients with hand osteoarthritis European League Against Rheumatism (EULAR) recommendations have been formulated in 2007. However, new evidence has emerged and therefore the recommendations have been updated by an international task force of experts, including rheumatologists, health professionals, plastic surgeon and patient representatives. First, a systematic literature review was performed, collecting evidence regarding non-pharmacological, pharmacological and surgical treatment options. Second, based on the evidence and expert opinion, five overarching principles were formulated, referring to treatment goal, information provision, individualised treatment, shared-decision making and need to consider multidisciplinary and multimodal treatment approaches. In addition ten recommendations were formulated, describing non-pharmacological, pharmacological and surgical options, and considerations about follow-up. Finally, a level of evidence, grade of recommendation and level of agreement were allocated by all experts to each statement. With the updated EULAR recommendations evidence-based up-to-date guidance can be provided on the management of hand OA. <h3>Disclosure of Interest</h3> M. Kloppenburg Grant/research support from: Pfizer, IMI-APPROACH, Consultant for: GlaxoSmithKline, Abbvie
Identification of a new VHL exon and complex splicing alterations in familial erythrocytosis or von Hippel-Lindau disease
Authors: Marion Lenglet, Florence Robriquet, Klaus Schwarz, Carme Camps, Anne Couturier, David Hoogewijs, Alexandre Buffet, Samantha J. L. Knight, Sophie Gad, Sophie Couvé, Franck Chesnel, Mathilde Pacault, Pierre Lindenbaum, Sylvie Job, Solenne Dumont, Thomas Besnard, Marine Cornec, Helene Dreau, Melissa Pentony, Erika Kvikstad, Sophie Deveaux, Nelly Burnichon, Sophie Ferlicot, Mathias Vilaine, Jean-Michaël Mazzella, Fabrice Airaud, Céline Garrec, Laurence Heidet, Sabine Irtan, Elpis Mantadakis, Karim Bouchireb, Klaus-Michael Debatin, Richard Redon, Stéphane Bezieau, Brigitte Bressac-de Paillerets, Bin Tean Teh, François Girodon, Maria-Luigia Randi, Maria Caterina Putti, Vincent Bours, Richard Van Wijk, Joachim R. Göthert, Antonis Kattamis, Nicolas Janin, Celeste Bento, Jenny C. Taylor, Yannick Arlot-Bonnemains, Stéphane Richard, Anne-Paule Gimenez-Roqueplo, Holger Cario, Betty Gardie
Journal: Blood (2018)
Evaluation of the Social Motivation Hypothesis of Autism
Authors: Caitlin C. Clements, Alisa R. Zoltowski, Lisa D. Yankowitz, Benjamin E. Yerys, Robert T. Schultz, John D. Herrington
Journal: JAMA Psychiatry (2018)

<h3>Importance</h3> The social motivation hypothesis posits that individuals with autism spectrum disorder (ASD) find social stimuli less rewarding than do people with neurotypical activity. However, functional magnetic resonance imaging (fMRI) studies of reward processing have yielded mixed results. <h3>Objectives</h3> To examine whether individuals with ASD process rewarding stimuli differently than typically developing individuals (controls), whether differences are limited to social rewards, and whether contradictory findings in the literature might be due to sample characteristics. <h3>Data Sources</h3> Articles were identified in PubMed, Embase, and PsycINFO from database inception until June 1, 2017. Functional MRI data from these articles were provided by most authors. <h3>Study Selection</h3> Publications were included that provided brain activation contrasts between a sample with ASD and controls on a reward task, determined by multiple reviewer consensus. <h3>Data Extraction and Synthesis</h3> When fMRI data were not provided by authors, multiple reviewers extracted peak coordinates and effect sizes from articles to recreate statistical maps using seed-based<i>d</i>mapping software. Random-effects meta-analyses of responses to social, nonsocial, and restricted interest stimuli, as well as all of these domains together, were performed. Secondary analyses included meta-analyses of wanting and liking, meta-regression with age, and correlations with ASD severity. All procedures were conducted in accordance with Meta-analysis of Observational Studies in Epidemiology guidelines. <h3>Main Outcomes and Measures</h3> Brain activation differences between groups with ASD and typically developing controls while processing rewards. All analyses except the domain-general meta-analysis were planned before data collection. <h3>Results</h3> The meta-analysis included 13 studies (30 total fMRI contrasts) from 259 individuals with ASD and 246 controls. Autism spectrum disorder was associated with aberrant processing of both social and nonsocial rewards in striatal regions and increased activation in response to restricted interests (social reward, caudate cluster:<i>d</i> = −0.25 [95% CI, −0.41 to −0.08]; nonsocial reward, caudate and anterior cingulate cluster:<i>d</i> = −0.22 [95% CI, −0.42 to −0.02]; restricted interests, caudate and nucleus accumbens cluster:<i>d</i> = 0.42 [95% CI, 0.07 to 0.78]). <h3>Conclusions and Relevance</h3> Individuals with ASD show atypical processing of social and nonsocial rewards. Findings support a broader interpretation of the social motivation hypothesis of ASD whereby general atypical reward processing encompasses social reward, nonsocial reward, and perhaps restricted interests. This meta-analysis also suggests that prior mixed results could be driven by sample age differences, warranting further study of the developmental trajectory for reward processing in ASD.
Abstract 441: Cerebral Vasospasm Depends On Rac-1 Mediated Oxidative Stress
Authors: Carmine Vecchione, Alessandro Landolfi, Alba Di Pardo, Umberto Bettarini, Giuseppe Lembo
Journal: Circulation (2007)

Subarachnoid hemorrhage is one of the most common events related to hypertensive crisis. The cerebral vasospasm is the complication of subarachnoid hemorrhage that causes more frequently death. Experimental evidences describe a direct relationship between hemolysed blood and vasospasm. Understand the molecular basis of vasospasm could help to reduce the mortality in patients with cerebrovascular damage. To clarify this aim, carotid and basilary arteries of rats were mounted on pressure myography and perfused at 100 mmHg. The vessels were placed in intracerebral fluid and entire (eb) or hemolysed blood (hb) was added. Our results showed that the eb did not modify the diameter of the vessel. Meanwhile, hb caused a clear vasoconstriction (max vasoconstriction: 10±1 vs 430±15, p&lt;0.01). Previous studies have hypothesized that oxidative stress could be involved in the cerebral vasospasm. So, the vessels were incubated with Tyron, an antioxidant agent. Our data demonstrated that the administration of Tyron reduced the vasoconstriction induced by hb (max vasoconstriction: 205±7 vs 410±12, p&lt;0.01) without influencing the effect of eb, suggesting an involvement of oxidative stress in the vascular response. Moreover, using lucigenin assay we found an increase in oxidative stress directly in the vessel treated with hb. One of the most important source of oxidative stress is the NADPH oxidase which needs Rac-1 to be activated. Our results demonstrated that the hb, and not the eb, was able to activate Rac-1 in the vessel, evaluated by Rac-1/PAK complex. To clearly define the role of Rac-1 in the vasoconstriction induced by hb, the vessels were transfected with an adenoviral vector containing Rac-1 dominant negative or an empty adenoviral vector. In this experimental condition, the vascular response induced by the hb was significantly blunted as compared to vessels treated with the empty adenovirus (max vasoconstriction: 180±7 vs 390±17, p&lt;0.01). Our results demonstrate that the vasoconstriction induced by the hb is induced by Rac-1-mediated oxidative stress. Thus, Rac-1 could represent the target of novel therapeutic strategies to reduce the cerebral vasospasm and so the mortality in patients with subarachnoid hemorrhage.