tbuckley/cabot-search huggingface dataset:
Advanced endoscopic submucosal dissection with magnetic bead-assisted traction based on gravity for a flat colorectal neoplasm with severe fibrosis
Authors: Johannes Bethge, Liansong Ye, Mark Ellrichmann, Naveed Khan, Zhe Feng, Stefan Schreiber, Bing Hu
Journal: Endoscopy (2018)

Endoscopic submucosal dissection (ESD) of colorectal lesions with severe submucosal fibrosis remains challenging. Fibrosis has also been implicated as a factor that increases the risk of incomplete or complicated dissection [1] [2] [3]. Several traction techniques have been described but remain to be established [4] [5].
Association of Physical Activity With Income, Race/Ethnicity, and Sex Among Adolescents and Young Adults in the United States
Authors: Sarah Armstrong, Charlene A. Wong, Eliana Perrin, Sara Page, Lauren Sibley, Asheley Skinner
Journal: JAMA Pediatrics (2018)

<h3>Importance</h3> Physical activity in youth is associated with adult health. Understanding the prevalence and factors of moderate to vigorous physical activity among adolescents and young adults will guide public health and policy efforts. <h3>Objectives</h3> To describe the current patterns of physical activity and duration among adolescents and young adults and to identify the direction and magnitude of associations between physical activity and income, race/ethnicity, and sex. <h3>Design, Setting, and Participants</h3> This cross-sectional secondary data analysis used the self-reported physical activity data of adolescents and young adults from the National Health and Nutrition Examination Survey from 2007 through 2016. This data set is a multistage probability sample of the noninstitutionalized US population and allows estimates that represent the US population. The years 2007 through 2016 were selected because of the consistent physical activity questions during this period. Adolescents and young adults aged 12 to 29 years who responded to the survey were included. Individuals who were underweight were excluded. Data analysis was performed from October 17, 2017, to April 27, 2018. <h3>Main Outcomes and Measures</h3> Self-reported physical activity duration and intensity. <h3>Results</h3> Of the 9472 participants, 4771 (50.4%) were males, and the weighted mean age (range) was 20.6 (12-19) years. Across all demographic categories, females reported less physical activity than did their male counterparts. White adolescent males were most likely (89.3%; 95% CI, 86.5%-92.1%) and black females aged 18 to 24 years were least likely (45%; 95% CI, 39.0%-51.0%) to report any physical activity. Among those who were active, black males aged 18 to 24 years reported the longest duration of activity (77.9 minutes per day; 95% CI, 66.4-89.3 minutes per day), and black females aged 25 to 29 years reported the shortest duration of activity (33.2 minutes per day; 95% CI, 28.1-38.2 minutes per day). In adjusted models, younger age, white race, and higher income were associated with greater physical activity. <h3>Conclusions and Relevance</h3> Female adolescents and young adults were not meeting the recommended guidelines for physical activity, and substantial disparities by race and income levels were noted. These data highlight opportunities for targeted physical activity programming and policy efforts.
Some methodological issues in the design and analysis of cluster randomised trials
Authors: Mohammad A Mansournia, Douglas G Altman
Journal: British Journal of Sports Medicine (2018)

Randomised trials are widely used for assessing the effect of interventions on outcomes, because on average randomisation balances covariates between treatment groups, even if those covariates are unobserved.1 2 In some situations, it is more convenient to assign treatments at random to clusters (eg, clubs, schools, teams and so on) into which individuals fall naturally. This design, which minimises the risk of contamination that would occur if individuals from the same cluster were randomised to different treatment groups, is a cluster randomised controlled trial .3 Several recent BJSM papers have reported cluster randomised trials.4–6 Among these, two studies assessed the effect of movement control exercise programmes on musculoskeletal injury and concussion risk in schoolboy and adult rugby players4 5 and a third assessed the effect of an exercise programme on the prevalence of shoulder problems in elite handball players.6 Here we review some important methodological aspects of cluster randomised controlled trials in the context of these studies. Some of these issues also affect individual randomised trials.

The most important methodological aspect of cluster randomised trial is that the effective sample size is less than the number of recruited individuals because the responses of individuals within the same cluster are likely to be positively correlated. As a result, the variance of the effect estimate in cluster randomised trials will be inflated compared with an individual randomised trial with the same sample size. This variance inflation factor, sometimes known as the design effect, increases with both intracluster correlation coefficient (ie, the proportion of the total variance of the effect estimate which can be explained by the variation between clusters) and average cluster size.

Although the value of intracluster correlation coefficient in cluster randomised trial tends to be small (typically <0.1), the resulting design effect can be quite substantial if the clusters are large. The …
SAT0683 A north-south worldwide gradient in systemic activity of primary sjÖgren syndrome: increased severe disease in patients from southern countries
Authors: S. Retamozo, N. Acar-Denizli, W. Fai Ng, M. Zeher, A. Rasmussen, R. Seror, X. Li, C. Baldini, J.-E. Gottenberg, D. Danda, L. Quartuccio, R. Priori, G. Hernandez-Molina, B. Armagan, A.A. Kruize, S.-K. Kwok, M. Wahren-Herlenius, S. Praprotnik, D. Sene, E. Bartoloni, R. Solans, M. Rischmueller, T. Mandl, Y. Suzuki, D. Isenberg, V. Valim, P. Wiland, G. Nordmark, G. Fraile, H. Bootsma, T. Nakamura, R. Giacomelli, V. Devauchelle-Pensec, B. Hofauer, M. Bombardieri, V. Fernandes Moça Trevisani, D. Hammenfors, S.G. Pasoto, T.A. Gheita, F. Atzeni, J. Morel, C. Vollenveider, P. Brito-Zerón, M. Ramos-Casals
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To analyse the influence of geolocation on the clinical systemic presentation of primary Sjögren syndrome (SjS) at diagnosis. <h3>Methods</h3> The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. Centres were classified by continent, with an additional north-south sub-classification according to latitude (&gt;or&lt;50’N in Europe, equator &gt;or &lt;in America and&gt;or&lt;30’N in Asia). Systemic involvement at diagnosis was retrospectively scored using the ESSDAI. <h3>Results</h3> The highest baseline ESSDAI scores were reported from Southern vs Northern countries in Europe (7.2 vs 4.6, p&lt;0.001), America (5.3 vs 3.5, p&lt;0.001) and Asia (6.3 vs 3.9, p&lt;0.001). In Europe, the frequency of activity in each domain was higher in Southern countries (in all domains except constitutional, p&lt;0.001). In America, Southern countries had the highest frequencies of active patients in constitutional, articular, cutaneous, pulmonary, PNS and CNS domains (p&lt;0.001 in all) and the lowest frequencies in lymphadenopathy (p=0.018) and biological (p&lt;0.001) domains. In Asia, patients from China had the highest frequency of activity in glandular, articular, pulmonary, muscular, haematological and biological and those from India in lymphadenopathy, cutaneous, renal and PNS. <h3>Conclusions</h3> This study provides the first evidence for a strong influence of geolocation on the systemic phenotype of primary SjS at diagnosis. Geographical determinants should be considered as key variables when systemic disease is scored. <h3>Disclosure of Interest</h3> None declared
The Endosomal Protein CEMIP Links WNT Signaling to MEK1–ERK1/2 Activation in Selumetinib-Resistant Intestinal Organoids
Authors: Hong Quan Duong, Ivan Nemazanyy, Florian Rambow, Seng Chuan Tang, Sylvain Delaunay, Lars Tharun, Alexandra Florin, Reinhard Büttner, Daniel Vandaele, Pierre Close, Jean-Christophe Marine, Kateryna Shostak, Alain Chariot
Journal: Cancer Research (2018)

Abstract MAPK signaling pathways are constitutively active in colon cancer and also promote acquired resistance to MEK1 inhibition. Here, we demonstrate that BRAFV600E-mutated colorectal cancers acquire resistance to MEK1 inhibition by inducing expression of the scaffold protein CEMIP through a β-catenin– and FRA-1–dependent pathway. CEMIP was found in endosomes and bound MEK1 to sustain ERK1/2 activation in MEK1 inhibitor–resistant BRAFV600E-mutated colorectal cancers. The CEMIP-dependent pathway maintained c-Myc protein levels through ERK1/2 and provided metabolic advantage in resistant cells, potentially by sustaining amino acids synthesis. CEMIP silencing circumvented resistance to MEK1 inhibition, partly, through a decrease of both ERK1/2 signaling and c-Myc. Together, our data identify a cross-talk between Wnt and MAPK signaling cascades, which involves CEMIP. Activation of this pathway promotes survival by potentially regulating levels of specific amino acids via a Myc-associated cascade. Targeting this node may provide a promising avenue for treatment of colon cancers that have acquired resistance to targeted therapies. Significance: MEK1 inhibitor–resistant colorectal cancer relies on the scaffold and endosomal protein CEMIP to maintain ERK1/2 signaling and Myc-driven transcription. Cancer Res; 78(16); 4533–48. ©2018 AACR.
FRI0559 Biomechanical properties of radial bone are different between auto-antibody positive and negative rheumatoid arthritis
Authors: F. Stemmler, D. Simon, A.-M. Liphardt, M. Englbrecht, J. Rech, A. Hueber, K. Engelke, G. Schett, A. Kleyer
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Functional properties of bone in rheumatoid arthritis (RA) are still not well characterised. <h3>Objectives</h3> This study aimed to define the impact of anti-citrullinated antibodies (ACPA) on biomechanical properties in RA. <h3>Methods</h3> Based on on high-resolution peripheral quantitative computed tomography (HR-pQCT) data from the distal radius of ACPA-positive RA (RA+), ACPA-negative RA (RA-) and healthy controls (HC) micro-finite element analysis (µFEA) was carried out to measure failure load and stiffness of bone.(<sup>1</sup> Comparisons of µFEA parameters between groups was calculated and multivariate models were used to determine the role of demographic, disease-specific and structural data of bone strength. <h3>Results</h3> A total of 276 subjects (96 RA+, 84 RA- and 96 HC) were analysed. Age and sex distributions were not significantly different between the three groups. In RA +but not in RA- failure load and stiffness were significantly decreased compared to HC (both p&lt;0.001). Lower bone strength affected both female and male RA +patients and was related to longer disease duration. Impaired bone strength was correlated with altered bone density and microstructural parameters, which were all decreased in RA+. Multivariate models showed that ACPA status (p=0.007) and sex (p&lt;0.001) were independently associated with reduced biomechanical properties of bone in RA. <h3>Conclusions</h3> In summary, µFEA showed that bone strength is significantly decreased in RA +but not in RA- disease. <h3>Reference</h3> [1] Macneil JA, Boyd SK. Bone strength at the distal radius can be estimated from high-resolution peripheral quantitative computed tomography and the finite element method. Bone2008;42(6):1203–13. <h3>Disclosure of Interest</h3> None declared
Intranasal administration of probiotic <i>Lactobacillus rhamnosus</i> GG prevents birch pollen‐induced allergic asthma in a murine model
Authors: I. Spacova, M. I. Petrova, A. Fremau, L. Pollaris, J. Vanoirbeek, J. L. Ceuppens, S. Seys, S. Lebeer
Journal: Allergy (2018)

Abstract Background There is an increasing interest in targeted application of probiotic bacteria for prevention and treatment of airway diseases, including allergies. Here, we investigated the beneficial effects of preventive intranasal treatment with probiotics Lactobacillus rhamnosus GG and L. rhamnosus GR‐1 in a mouse model of allergic asthma. Methods Lactobacillus rhamnosus was administered intranasally eight times on days 1‐4 and 8‐11 at 5 × 10 8 CFU/dose, followed by a 2‐week asthma induction protocol with birch pollen extract on alternating days. Effects of preventive treatment were analyzed based on serum antibody levels, bronchoalveolar lavage cell counts, lung histology, lung cytokine levels, and airway hyperreactivity. Colonization and translocation of L. rhamnosus were assessed by bacterial cell counts in nasal mucosa, fecal samples, cervical lymph nodes, and blood. Binding of fluorescent L. rhamnosus to fixed murine nasal mucosal cells and airway macrophages was visualized by fluorescence microscopy. Results Transient colonization of the murine upper airways by L. rhamnosus GG was demonstrated and was approximately ten times higher compared to L. rhamnosus GR‐1. Marked binding of fluorescent L. rhamnosus GG to murine nasal mucosal cells and airway macrophages was visualized. Preventive treatment with L. rhamnosus GG (but not L. rhamnosus GR‐1) resulted in a significant decrease in bronchoalveolar lavage eosinophil counts, lung interleukin‐13 and interleukin‐5 levels, and airway hyperreactivity. A tendency toward a decrease in serum Bet v 1‐specific immunoglobulin G1 was likewise observed. Conclusion Intranasally administered L. rhamnosus GG prevents the development of cardinal features of birch pollen‐induced allergic asthma in a strain‐specific manner.
Degradation of c-Myc by WP1130 Through Activation of a Novel Proteasomal-Dependent Pathway
Authors: Geoffrey A. Bartholomeusz, Nicholas Donato, Waldemar Priebe, William P. Tansey, Moshe Talpaz
Journal: Cancer Research (2006)

3022  The c-Myc proto-oncogene is a central regulator of key cellular processes such as differentiation, regulation of the G1-to-S-phase transition, proliferation, maintenance of cell size, angiogenesis, and apoptosis. c-Myc is deregulated in a variety of types of cancer, including melanomas, myelomas, Burkitt’s lymphoma, and breast, prostate, and colon cancer, and this deregulation often correlates with highly aggressive, poorly differentiated tumors and poor prognosis. Compounds that inhibit c-Myc activity specifically in tumor cells are being actively sought for possible development as anticancer therapy. In one such search, screening a library of small molecular weight compounds for their ability to induce the degradation of critical transcription factors and tyrosine kinases led to the design and synthesis of WP1130, a compound that reduces Jak2, Bcr/Abl, and c-Myc protein stability. The purpose of this study was to identify the mechanisms mediating the WP1130-induced downregulation of c-Myc. Treatment of multiple myeloma (MM-1) cells with WP1130 led to rapid downregulation of the c-Myc protein (tested by Western blotting) but did not inhibit transcription of c-Myc (tested by Northern blotting). Further, WP1130 did not degrade c-Myc mRNA that had been synthesized in an in-vitro transcription and translation assay. Collectively, these observations indicate that WP1130 downregulates c-Myc by activating a proteolytic pathway. Because endogenous c-myc is degraded by the ubiquitin-mediated proteasomal system, we next investigated whether a similar mechanism mediated WP1130-induced degradation of c-Myc. Indeed, proteasome inhibitors blocked the ability of WP1130 to degrade c-Myc, indicating that WP1130-induced c-Myc degradation depends on the proteasome. To identify the region of c-Myc necessary for its WP1130-induced, proteasome-mediated degradation, we treated HeLa cells that ectopically expressed either wild-type c-Myc or a series of scanning deletion mutants with WP1130 and assessed c-Myc expression by Western blot analysis. Expression of wild-type c-Myc protein and that of all the deletion mutants except one was strongly downregulated in the presence of WP1130. The c-Myc mutant that was unaffected by WP1130 had a deletion at the c-terminus_a region distinct from all others known to be involved in the proteasomal-mediated downregulation of c-Myc. Our ongoing work involves identifying the signaling molecules that participate in this novel, proteasome-dependent pathway.
Adam Gazzaley, MD, PhD: Developing Prescribable Video Games
Authors: Jennifer Abbasi
Journal: JAMA (2018)

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OP0108 Diet induced metabolic changes in an osteoarthritis mouse model
Authors: M.-L. Hülser, C. Schreiyaeck, Y. Luo, A. Bozec, G. Schett, U. Müller-Ladner, E. Neumann
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Adipose tissue is not only an energy depot, but also secrets bioactive factors such as adipokines. Several of these factors are known to regulate immune responses. Osteoarthritis (OA) is one of the most common joint diseases with obesity being a well known risk factor. Therefore, an obesity model (High-fat diet, HFD) was combined with an established model for OA (DMM, destabilisation of the medial meniscus) to evaluate the role of adipokines in this setting. <h3>Objectives</h3> This work evaluates the influence of different adipokines on OA progression and obesity comparing systemic vs local effects at different time points. <h3>Methods</h3> The study was performed in C57Bl/6 mice fed with HFD or ND (normal diet) prior to OA induction. Mice were sacrificed and analysed 4, 6 and 8 weeks after surgery. For systemic analysis, sera were evaluated for adipokines such as adiponectin, leptin and visfatin and inflammatory markers. Diet induced systemic changes were also analysed using a fatty liver score and evaluation of crown-like structures (CLS) in adipose tissue. OA progression was scored and quantified based on histological stainings of the joints (H/E, safranin O). Immunohistochemical stainings of the joints were performed to evaluate local distribution of adipokine positive cells and the respective cell types. Metabolic parameters were correlated to the local progression of OA. <h3>Results</h3> The numbers of CLS were significantly lower comparing HFD (0.2±0.1553, n=7) with ND (5.219±0.9831, n=8) in mice. Fatty-liver score was significantly higher in HFD compared to ND. OA induction was significant at every timepoint vs healthy control and higher in HFD (e.g.: OA score at 6 weeks HFD 3.7 vs ND 1.4). In the OA groups, there was a positive correlation between bodyweight and OA score (r²=0.33). Correlation level of OA score with liver score or serum leptin level was low, even though leptin was significantly induced by HFD. However, DMM decreased leptin levels at all time points, independent from diet (e.g. 4 weeks: HFD healthy 18.4 ng/ml vs HFD DMM 3.7 ng/ml). The different parameters for metabolic changes (fatty liver score and bodyweight) were positively correlated with serum leptin level. HFD, DMM or the combination of both did not show significant effects on serum levels of adiponectin, visfatin or IL-6. Local adipokine secretion in the joints was independent from systemic metabolism parameters. <h3>Conclusions</h3> Our data show that similar to observations in humans, OA is deteriorated by HFD which correlates mainly with the bodyweight and to a lower extend with metabolic changes induced by obesity. Local adipokine expression was especially detectable in the damaged menisci showing increased amounts of adiponectin and leptin producing cells. Interestingly, local adipokine expression was independent from systemic adipokine levels. <h3>Disclosure of Interest</h3> None declared
Unilateral retinopathy in a patient with diabetes and coronary heart disease
Authors: Maria Fernanda Abalem, Kim A Eagle, Rajesh C Rao
Journal: BMJ (2018)

A 69 year old man with type 2 diabetes mellitus, obesity, hypertension, and coronary artery disease was referred for diabetic retinopathy screening. He was also undergoing evaluation for transient ischaemic attack after experiencing dizziness and intermittent weakness in the left hand over the past six months. Visual acuities and intra-ocular pressures were normal, and slit lamp examination of the anterior segment of both eyes was unremarkable. Funduscopic examination (figs 1, 2) and wide field fluorescein angiography (fig 3) revealed unilateral retinopathy in the left eye. These unilateral findings prompted concern for carotid disease. Doppler carotid ultrasonography (fig 4) and computed tomography angiography found complete occlusion of the left internal carotid artery.



Fig 1 
Ultrawide field …
Image Gallery: Cervical lymphadenitis as an unusual presentation of disseminated coccidioidomycosis
Authors: R.-J. Wang, X.-W. Wang, K. Shibuya, R.-Y. Li
Journal: British Journal of Dermatology (2018)

Funding sources: none. Conflicts of interest: none to declare. Dear Editor, A 20‐year‐old woman presented with an 8‐month history of intermittent fever and cough and a 5‐month history of enlarging cervical masses accompanied by a nodule on her right wrist (a, b). She was previously healthy and had always lived in China except for a short‐term study experience in California 1 year earlier. A needle biopsy obtained from her neck mass revealed multiple round and oval‐shaped spherules with suspected endospores (d). The patient was treated with intravenous liposomal amphotericin B for 8 weeks, and continued oral itraconazole for 1·5 years with complete remission of the lesions (c). Disseminated coccidioidomycosis with cervical involvement is uncommon and might be diagnostically challenging to doctors, especially in non‐endemic regions.1