tbuckley/cabot-search huggingface dataset:
Validity of the <scp>EQ</scp> ‐5D in patients with pemphigus vulgaris and pemphigus foliaceus
Authors: B. Tamási, V. Brodszky, M. Péntek, L. Gulácsi, K. Hajdu, M. Sárdy, A. Szegedi, Z. Bata‐Csörgő, Á. Kinyó, F. Rencz
Journal: British Journal of Dermatology (2018)

No studies to date have employed the EuroQoL EQ-5D questionnaire to assess health-related quality of life (HRQoL) in patients with pemphigus.To evaluate the HRQoL of patients with pemphigus by the EQ-5D and to analyse the convergent and known-groups validity of the EQ-5D in this patient population.Between 2014 and 2017, a multicentre cross-sectional study was carried out. Outcome measures included the five-level EQ-5D (EQ-5D-5L), Dermatology Life Quality Index (DLQI), Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and an average pain intensity visual analogue scale (VAS) for the past 3 months.In total, 109 consecutive patients with pemphigus participated in the study (mean age 57 years; 64% women). Among the EQ-5D dimensions, the most problems were reported regarding pain/discomfort (50%), mobility (43%) and anxiety/depression (43%). No significant difference was found in mean EQ-5D index scores between patients with pemphigus vulgaris and those with pemphigus foliaceus (0·81 vs. 0·86, P = 0·14). The mean EQ-5D index scores of patients with limited, moderate, significant and extreme pemphigus were 0·88, 0·82, 0·72 and 0·67, respectively (P = 0·001). The number of comorbidities was associated with greater impairment in EQ-5D index scores (P < 0·001). DLQI (rs = -0·62, P < 0·001) and the average pain intensity VAS (rs = -0·59, P < 0·001) more strongly correlated with the EQ-5D index scores than did ABSIS (rs = -0·40, P < 0·001).This is the first study employing the EQ-5D questionnaire in pemphigus. The EQ-5D is a valid measure of HRQoL in patients with pemphigus that can be useful both in clinical practice and in economic evaluations to assess the health gains associated with new effective treatments.
Colorectal cancer gene expression profiling using nanostring nCounter analysis.
Authors: Kristen Keon Ciombor, Natasha G Deane, Keeli B Lewis, Xi Chen, Bing Zhang, Mary Kay Washington, Chanjuan Shi, R. Daniel Beauchamp
Journal: Journal of Clinical Oncology (2013)

3555 Background: A more accurate method of identifying stage 2 and 3 colorectal cancer (CRC) patients at highest risk for recurrence after surgical resection is needed. Gene expression signatures utilizing microarray-derived gene expression data from fresh frozen primary CRCs to predict risk of recurrence have been developed by us and others. Advances in technology platforms for gene expression measurements and their applicability to formalin-fixed, paraffin-embedded (FFPE) specimens offer new opportunity to develop clinically useful diagnostics based on molecular profiles. Methods: 58 patient FFPE samples of all stages stored from 1-12 years were collected from the Vanderbilt GI SPORE Translational Pathology and Imaging Core and annotated with appropriate clinicopathologic data. 414 genes were selected from our 34-gene prognostic classifier and other published CRC gene signatures, as well as gene elements associated with intestinal stem cell biology and epithelial-to-mesenchymal transition (EMT). RNA was extracted from the tumors, and gene expression analysis was completed using the nCounterplatform. Results: Quality of extracted RNA from tumor blocks was similar among the tumors and adequate for analysis. No significant differences were seen in signal strength (p=0.94, Kruskal-Wallis test) or intra-class variation (correlation coefficient = 0.99) across material extracted from new and old blocks. Fold change values for the 70 most highly differentially expressed genes on the nCounter platform correlated well with Affymetrix U133 plus 2 microarray (R 2 =0.819). Genes associated with EMT clustered according to prognosis, with poorer prognoses seen in patients with high TWIST expression or low E-cadherin and SMAD4 expression. There was a trend toward better survival outcomes with high expression of E-cadherin and SMAD4 (p=0.072, log-rank test). Conclusions: This preliminary study demonstrates the feasibility of this approach to determine gene expression patterns in FFPE tumor tissue samples. Our data suggest that this approach may be applied to identify clinically applicable prognostic gene expression profiles that may be validated in archived patient samples that are well annotated with patient outcome data.
A Visual-Cue-Dependent Memory Circuit for Place Navigation
Authors: Han Qin, Ling Fu, Bo Hu, Xiang Liao, Jian Lu, Wenjing He, Shanshan Liang, Kuan Zhang, Ruijie Li, Jiwei Yao, Junan Yan, Hao Chen, Hongbo Jia, Benedikt Zott, Arthur Konnerth, Xiaowei Chen
Journal: Neuron (2018)
BAI1 Suppresses Medulloblastoma Formation by Protecting p53 from Mdm2-Mediated Degradation
Authors: Dan Zhu, Satoru Osuka, Zhaobin Zhang, Zachery R. Reichert, Liquan Yang, Yonehiro Kanemura, Ying Jiang, Shuo You, Hanwen Zhang, Narra S. Devi, Debanjan Bhattacharya, Shingo Takano, G. Yancey Gillespie, Tobey Macdonald, Chalet Tan, Ryo Nishikawa, William G. Nelson, Jeffrey J. Olson, Erwin G. Van Meir
Journal: Cancer Cell (2018)
SAT0670 Dynamic thiol/disulfide homeostasis as a novel oxidative marker in behÇet’s disease
Authors: S. Can Sandikci, S. Colak, A. Omma, M.E. Enecik, Z. Ozbalkan, S. Neselioglu, O. Erel
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Behçet's disease (BD) is a relapsing systemic inflammatory disorder of unknown etiology.<sup>1</sup> <h3>Objectives</h3> In this study, we aimed to evaluate the relationship between the thiol-disulfide balance and disease activity and organ involvement in BD. <h3>Methods</h3> One hundred fifty (150) patients with BD and 100 age-gender matched healty controls were included in the study. Disease activity was assessed with the BD Current Activity Form (BDCAF) score. Serum levels of native thiol (NT), total thiol (TT), and disulfide were measured and the disulfide/native thiol, disulfide/total thiol and native thiol/total thiol levels were calculated for the patient and control groups. <h3>Results</h3> NT, TT, NT/TT values of the BD patients were significantly lower than those of the control group. The disulfide/NT, disulfide/TT values of BD patients were higher compared to the control group and the disulfide value of the BD group was slightly higher compared to the control group (table 1). No correlation was determined between thiol levels and disease activity and organ involvement in BD. <h3>Conclusions</h3> In patients with Behcet's disease, the dynamic thiol-disulfide homeostasis balance shifted towards disulfide formation due to thiol oxidation. It may be used as a novel marker in BD because it is easy, practical, fully automated and relatively inexpensive. <h3>Acknowledgements</h3> The authors thank staff of Ankara Numune Training and Research Hospital, Department of Rheumatology for their generous friendly assistance in every step of this study. <h3>Disclosure of Interest</h3> None declared
Fabrication and Characterization of Chitosan–Hyaluronic Acid Scaffolds with Varying Stiffness for Glioblastoma Cell Culture
Authors: Ariane E. Erickson, Sheeny K. Lan Levengood, Jialu Sun, Fei‐Chien Chang, Miqin Zhang
Journal: Advanced Healthcare Materials (2018)

The invasive and recurrent nature of glioblastoma multiforme (GBM) is linked to a small subpopulation of cancer cells, which are self-renewing, resistant to standard treatment regimens, and induce formation of new tumors. Matrix stiffness is implicated in the regulation of cell proliferation, drug resistance, and reversion to a more invasive phenotype. Therefore, understanding the relationship between matrix stiffness and tumor cell behavior is vital to develop appropriate in vitro tumor models. Here, chitosan-hyaluronic acid (CHA) polyelectrolyte complex scaffolds are fabricated with statistically significant stiffness variances to characterize the effect of scaffold stiffness on morphology, proliferation, drug resistance, and gene expression in human glioblastoma cells (U-87 MG). All scaffolds support GBM proliferation over a 12-day culture period, yet larger spheroids are observed in scaffolds with higher stiffness. Additionally, GBM cells cultured in stiffer CHA scaffolds prove significantly more resistant to the common chemotherapeutic temozolomide. Moreover, the stiffer 8% CHA scaffolds exhibit an increase in expression of drug resistance and invasion related genes compared to 2D culture. CHA scaffolds present a tunable microenvironment for enhanced tumor cell malignancy and may provide a valuable in vitro microenvironment for studying tumor progression and screening anticancer therapies.
AB1336 Musculoskeletal disorders in hemodialysis patients: different disease clustering according to age and dialysis vintage
Authors: N. Ziade, S. Hage, V. Hage, N. Khoury, H. Azar, D. Chelala
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The number of patients suffering from stage 5 Chronic Kidney Disease is constantly increasing and their life expectancy has improved due to the hemodialysis technique. Musculoskeletal disorders remain a major problem in long term hemodialysis patients. Frequency and severity of these manifestations increase with the length of the dialysis. <h3>Objectives</h3> To identify diseases clustering profiles of musculoskeletal disorders in hemodialysis patients. <h3>Methods</h3> All adult patients in the hemodialysis centre were included in this cross-sectional study. For each patient, we filled a data collection sheet including basic demographic characteristics, musculoskeletal symptoms, biologic parameters and treatments. Musculoskeletal disorders were classified by a rheumatologist into pre-defined diagnostic categories: Osteoarthritis, Fractures, Tendinopathies, Carpal Tunnel Syndrome, Crystal deposition disease and Others. Prevalences were presented and a cluster analysis was performed. <h3>Results</h3> Eighty-nine patients were included (table 1). Mean age was 67.5±12 years. 43.8% were female. Dialysis vintage was 5.7±5.37 years. Musculoskeletal symptoms were reported by 76.4% of the patients. Pain was the most frequent symptom (44.9%). The main disorders were osteoarthritis (53.9%), fracture (27%), tendinopathy (22.5%), carpal tunnel syndrome (18%), and chondrocalcinosis (9%). Musculoskeletal symptoms were significantly related to the dialysis vintage and age (p=0.044, p=0.035 respectively). All disorders categories were significantly associated with dialysis vintage, particularly increasing after the seventh year of dialysis. Cluster analysis identified three patient profiles: younger with low calcium levels, younger but long dialysis vintage with osteoarthritis and carpal tunnel syndrome, older and long dialysis vintage with fractures (figure 1). <h3>Conclusions</h3> The prevalence of the musculoskeletal manifestations is high (76.4%) in the hemodialysis population. Musculoskeletal disorders seem to cluster differently according to age and dialysis vintage. <h3>Acknowledgements</h3> Dr Ghada Abi Karam and Dr Fouad Fayad. <h3>Disclosure of Interest</h3> None declared
Peripheral serotonin receptor 2B and transient receptor potential channel 4 mediate pruritus to serotonergic antidepressants in mice
Authors: Sang Hoon Lee, Pyung Sun Cho, Raquel Tonello, Han Kyu Lee, Jun Ho Jang, Gi Yeon Park, Sun Wook Hwang, Chul-Kyu Park, Sung Jun Jung, Temugin Berta
Journal: Journal of Allergy and Clinical Immunology (2018)
Improved Titers against Influenza Drift Variants with a Nanoparticle Vaccine
Authors: Vivek Shinde, Louis Fries, Yukun Wu, Sapeckshita Agrawal, Iksung Cho, D Nigel Thomas, Michelle Spindler, Elizabeth Lindner, Timothy Hahn, Joyce Plested, David Flyer, Michael J Massare, Bin Zhou, Amy Fix, Gale Smith, Gregory M Glenn
Journal: New England Journal of Medicine (2018)

Improving the Influenza Vaccine Many approaches are being sought to improve the vaccine against influenza virus. In this report, data on the immunogenicity of a nanoparticle vaccine with a baculovi...
SP0035 Inflammation-induced formation of fat associated lymphoid clusters
Authors: J. Caamano
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Fat-associated lymphoid clusters (FALCs) are atypical lymphoid tissues located on adipose tissues in mucosal surfaces such as the mesenteries, omentum, mediastinum, pericardium, and gonadal fat in humans and mice. FALCs were originally identified in mouse and human mesenteries due to that they contain a high number of type 2 innate lymphoid cells (ILC). Our work has shown that FALCs contain B1, B2 and T lymphocytes as well as myeloid and other innate immune cell populations.<sup><sup>1,2</sup></sup> Inflammation induces the rapid formation of FALCs and significant changes in cellular composition. Immunizations have shown the development of adaptive immune responses including B cells undergoing a germinal centre reaction in mesenteric FALCs emphasising their function on local immunity. Our recent results show that helminth o bacterial infections induce a significant increase in proliferation of ILC in FALCs and a massive expansion in the number of clusters at early time points. A recent report has demonstrated that mesenteric FALCs act as a reservoir of CD8 +T resident memory cells (Trm) that have been generated following infections with bacteria or parasites.<sup><sup>3</sup></sup> Our current working model is that FALCs have a dual role during immune responses. At the initial stages of infection or inflammation FALCs support the activation and proliferation of innate lymphoid cells. At later stages FALCs act as reservoirs of tissue resident memory T cells through their stromal cell expression of survival factors and their association with adipocytes to support Trm metabolism and survival. Understanding what signals and cells are essential to FALC formation in homeostasis and following inflammation or infection will allow the development of therapies to reduce or prevent FALC formation during chronic inflammation and autoimmune diseases. <h3>Reference</h3> [1] Benezech C, et al. Nat Immunol2015;16:819.3. [2] Cruz-Migoniet al. Front. Immunol2016. https://www.frontiersin.org/articles/10.3389/fimmu.2016.00612/full#B27 [3] Hanet al. Immunity 2017;47:1154. <h3>Disclosure of Interest</h3> None declared
AB0705 Long-term outcomes and prognostic factors associated with aortic valve surgery in patients with takayasu arteritis and aortic valveregurgitation
Authors: S.H. Nam, O.C. Kwon, W.J. Seo, Y.-G. Kim, C.-K. Lee, B. Yoo, S. Hong
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Some patients with Takayasu arteritis (TA) have aortic valve (AV) involvement, which can lead to aortic regurgitation (AR). However, data on the long-term outcomes, including survival of TA patients with AR, are lacking. Moreover, previous studies were limited to patients who underwent AV surgery. <h3>Objectives</h3> This study aimed to characterise the long-term outcomes and clinical characteristics of TA patients with AR regardless of whether they underwent surgical intervention. <h3>Methods</h3> Medical records of patients with <sup>TA between January 1995</sup> and December 2015 were retrospectively reviewed. AR was diagnosed using transthoracic echocardiography. Poor outcomes were defined as all-cause death and major adverse cardiac and cerebrovascular events (MACCE). Multivariate analysis was performed to determine the factors affecting poor prognosis in the surgical group. <h3>Results</h3> Of the total 105 patients with TA and AR, 41 (39.0%) underwent AV surgery. Among patients who underwent AV surgery, inflammation values (Erythrocyte sedimentation rate, 62.07±31.8 mm/hr vs. 39.16±28.4 mm/hr; C-reactive protein, 3.66±4.1 mg/dL vs. 0.92±1.7 mg/dL), AR degree (3.56±0.7 grade vs. 2.08±1.0 grade), and sinus diameter (37.24±5.7 mm vs. 33.22±4.5 mm) were significantly higher than in those who did not undergo AV surgery. Long-term survival and freedom from MACCE were not significantly different between the groups (10 year survival, 84.3% vs. 79.4%; p=0.827; 10 year event-free survival, 51.8% vs. 71.2%; p=0.29). Twelve of the 41 patients who underwent AV surgery had a poor outcome during follow-up (median, 92.5 months; IQR, 54.5–183.5), and eight of them had a recurrence of AR requiring reoperation. Multivariate Cox analysis revealed that coronary disease [hazard ratio (HR), 4.234; 95% confidence interval (CI), 1.381–12.979; p=0.012], LV dysfunction (HR, 3.387; 95% CI, 1.143–10.042; p=0.028), and impaired renal function (HR, 19.983; 95% CI, 3.480–114.731; p=0.001) were significant risk factors associated with poor outcomes at follow-up (table 1). <h3>Conclusions</h3> In patients with TA with AV involvement, there were no significant differences between long-term survival rate and event-free survival (MACCE) among those who had or had not undergone AV surgery. In the surgical group, the prognosis was poor when coronary artery disease, LV dysfunction, and renal impairment were present at the time of surgery. <h3>Disclosure of Interest</h3> None declared
Belimumab in kidney transplantation: an experimental medicine, randomised, placebo-controlled phase 2 trial
Authors: Gemma D Banham, Shaun M Flint, Nicholas Torpey, Paul A Lyons, Don N Shanahan, Adele Gibson, Christopher J E Watson, Ann-Marie O'Sullivan, Joseph A Chadwick, Katie E Foster, Rachel B Jones, Luke R Devey, Anna Richards, Lars-Peter Erwig, Caroline O Savage, Kenneth G C Smith, Robert B Henderson, Menna R Clatworthy
Journal: The Lancet (2018)
FRI0190 Relationship between faecal calprotectin, hlab-27 and acute phase reactants in patients with spondyloarthritis without prior diagnosis of inflammatory bowel disease
Authors: C. Ramos Giraldez, M. Espinosa Malpartida, C. Merino Argumánez, B. Ruíz Antorán, J. Campos Esteban, C. Barbadillo Mateos, H. Godoy Tundidor, B. Agudo Castillo, Y. González Lama, J.L. Andréu Sánchez, J. Sanz Sanz
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Faecal calprotectin (FC) is a biomarker of inflammatory bowel activity widely used in the diagnosis and follow-up of inflammatory bowel disease (IBD). Microscopic intestinal inflammation is described in approximately 50% of patients with spondyloarthritis (SpA), and it is associated with more severe disease. <h3>Objectives</h3> The purpose of this study was to describe the possible relationship between FC, HLAB27 and acute phase reactants in patients diagnosed of SpA without clinical suspicion or prior diagnosis of IBD. <h3>Methods</h3> Unicentric, cross-sectional observational study with prospective clinical data collection. We included consecutively selected patients in the Rheumatology Clinic diagnosed of SpA who fulfilled ASAS criteria and did not have digestive symptoms suggestive of IBD (chronic diarrhoea, rectal bleeding, perianal disease or chronic abdominal pain persistent/recurrent). Demographic, clinical and analytical data from SpA (Uveitis, HLAB27, acute phase reactants), treatments and FC were collected and a FC cut-off point &gt;50 MG/kg was determined. For patients on NSAIDS suspension was recommended two weeks prior to collection of stool samples. The study was approved by the centre's Ethics Committee for Clinical Trials. <h3>Results</h3> Ninety-nine patients were included. 50% male, average age 46±11 years old. 3.7±2.5 BASDAI. 79% HLA-B27 positive, 31% had elevated levels of ESR, 9% elevated CRP (&gt;10 mg/L). 49 patients (49.5%) had high levels of FC, with mean levels of 276 mg/Kg (range 52–3,038). HLAB27 positive patients had significantly higher FC levels than HLAB27 negative patients (160 mg/kg vs 98 mg/kg; p&lt;0.05). There were no differences in relation to the history of uveitis. Patients with high FC had significantly higher CRP levels than patients with normal FC (6.7 mg/L vs. 3.2 mg/L; p&lt;0.05), in accordance with these results from the group of patients with CRP levels&gt;10 mg/L, the percentage of FC elevation was 78% vs. 47% of patients with CRP &lt;10 mg/L. There were no significant differences in relation to ESR. <h3>Conclusions</h3> Patients with spondyloarthritis (ASAS criteria), HLAB27 positive and elevated CRP have higher levels of faecal calprotectin, a biomarker of inflammatory bowel activity, which may indicate that inflammatory activity in SpA might be associated with subclinical intestinal inflammation. <h3>Disclosure of Interest</h3> None declared
Construction of humanized anti-HER2 single-chain variable fragments (husFvs) and achievement of potent tumor suppression with the reconstituted husFv-Fdt-tBid immunoapoptotin
Authors: Qing Ou-Yang, Bo Yan, Ang Li, Zhi-Song Hu, Jian-Nan Feng, Xin-Xin Lun, Ming-Ming Zhang, Meng-De Zhang, Kai-Chun Wu, Fang-Fang Xue, An-Gang Yang, Jing Zhao
Journal: Biomaterials (2018)
Glucocorticoids and Bone: Consequences of Endogenous and Exogenous Excess and Replacement Therapy
Authors: Rowan S Hardy, Hong Zhou, Markus J Seibel, Mark S Cooper
Journal: Endocrine Reviews (2018)

Osteoporosis associated with long-term glucocorticoid therapy remains a common and serious bone disease. Additionally, in recent years it has become clear that more subtle states of endogenous glucocorticoid excess may have a major impact on bone health. Adverse effects can be seen with mild systemic glucocorticoid excess, but there is also evidence of tissue-specific regulation of glucocorticoid action within bone as a mechanism of disease. This review article examines (1) the role of endogenous glucocorticoids in normal bone physiology, (2) the skeletal effects of endogenous glucocorticoid excess in the context of endocrine conditions such as Cushing disease/syndrome and autonomous cortisol secretion (subclinical Cushing syndrome), and (3) the actions of therapeutic (exogenous) glucocorticoids on bone. We review the extent to which the effect of glucocorticoids on bone is influenced by variations in tissue metabolizing enzymes and glucocorticoid receptor expression and sensitivity. We consider how the effects of therapeutic glucocorticoids on bone are complicated by the effects of the underlying inflammatory disease being treated. We also examine the impact that glucocorticoid replacement regimens have on bone in the context of primary and secondary adrenal insufficiency. We conclude that even subtle excess of endogenous or moderate doses of therapeutic glucocorticoids are detrimental to bone. However, in patients with inflammatory disorders there is a complex interplay between glucocorticoid treatment and underlying inflammation, with the underlying condition frequently representing the major component underpinning bone damage.