tbuckley/cabot-search huggingface dataset:
Nitric Oxide Therapy for Diabetic Wound Healing
Authors: Maggie J. Malone‐Povolny, Sara E. Maloney, Mark H. Schoenfisch
Journal: Advanced Healthcare Materials (2019)

Abstract Nitric oxide (NO) represents a potential wound therapeutic agent due to its ability to regulate inflammation and eradicate bacterial infections. Two broad strategies exist to utilize NO for wound healing; liberating NO from endogenous reservoirs, and supplementing NO from exogenous sources. This progress report examines the efficacy of a variety of NO‐based methods to improve wound outcomes, with particular attention given to diabetes‐associated chronic wounds.
Abstract 16243: Pre-ESRD Serum HDL Cholesterol Levels and One Year Post-ESRD Mortality in US Incident Hemodialysis Veterans: A Transition of Care in CKD Study
Authors: Hamid Moradi, Christina Park, Melissa Soohoo, Moti L Kashyap, Nosratola D Vaziri, Csaba P Kovesdy, Kamyar Kalantar-Zadeh, Elani Streja
Journal: Circulation (2017)

Introduction: Elevated serum concentrations of HDL cholesterol (HDL-c) in prevalent hemodialysis (HD) patients can be paradoxically associated with worse outcomes. However, many believe that serum ...
SP0038 Raiising awareness of invisible illnesses in schools and education
Authors: S. Ainsworth
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> RAiISE is a user-led research project inspired by the negative experiences that young people face while studying and living with an invisible illness. Many young people who live with chronic illnesses look no different to their healthy peers. The invisible nature of some illnesses can often lead to an invisible struggle, leading to misunderstandings, particularly in the case of young people. It can be a huge burden on the chronically ill to make the invisible, visible to others. <h3>Objective</h3> The main objective of RAiISE is to improve the standard of care given to young people with invisible illnesses in school and college and to create a resource to teach education professionals a series of strategies and techniques to support their students. RAiISE will also offer support to young people with invisible illnesses and aim to empower them to take control of their own health. <h3>Methods</h3> A young patient of Alder Hey NHS Children's Foundation Trust decided to raise awareness of living with an invisible illness. A network of young people, parents, education and health professionals was created and a series of workshop and focus groups allowed each stakeholder to share their experiences and expertise as they inspired and advised the production of the RAiISE information pack. It is important that young people are able to shape research based on their lived experiences. Several international charities and organisations have offered support and knowledge in advising the process. <h3>Results</h3> At early workshop meetings, young people with invisible illnesses and their parents were able to offer personal accounts and experiences which highlighted that the most common themes were problems with communication and trust, as well as difficulty in understanding the erratic nature of many chronic illnesses. From this research, a draft information pack was written by the RAiISE committee, which was later presented to young people, parents, health and education professionals and charity representatives. All stakeholders were able to offer their expertise from their respective fields. Feedback was overwhelmingly positive and any adjustments are to be made in the coming weeks. The final pack will be completed and ready for distribution by the end of summer 2018. <h3>Conclusion</h3> The project has been a successful example of young patient led research and highlights the importance of self-management in young people living with invisible chronic illnesses. The collaboration between young people, parents, and education and health professionals has highlighted the necessity for cooperation between all stakeholders for the benefit of the young person. <h3>Disclosure of Interest</h3> None declared
Introduction to the Theme “New Therapeutic Targets”
Authors: Paul A. Insel, Susan G. Amara, Terrence F. Blaschke, Urs A. Meyer
Journal: The Annual Review of Pharmacology and Toxicology (2019)

"New Therapeutic Targets" is the theme of articles in the Annual Review of Pharmacology and Toxicology, Volume 59. Reviews in this volume discuss targets for a variety of conditions in need of new therapies, including type 2 diabetes, heart failure with preserved ejection fraction, obesity, thyroid-associated ophthalmopathy, tinnitus, multiple sclerosis, Parkinson's disease and other neurodegenerative diseases, pain, depression, post-traumatic stress disorder, muscle wasting diseases, cancer, and anemia associated with chronic renal disease. Numerous articles in this volume focus on the identification, validation, and utility of novel therapeutic targets, in particular, ones that involve new or unexpected molecular entities. This theme complements several previous themes, including "New Approaches for Studying Drug and Toxicant Action: Applications to Drug Discovery and Development," "Precision Medicine and Prediction in Pharmacology," and "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology."
Loss of function of NCOR1 and NCOR2 impairs memory through a novel GABAergic hypothalamus–CA3 projection
Authors: Wenjun Zhou, Yanlin He, Atteeq U Rehman, Yan Kong, Sungguan Hong, Guolian Ding, Hari Krishna Yalamanchili, Ying-Wooi Wan, Basil Paul, Chuhan Wang, Yingyun Gong, Wenxian Zhou, Hao Liu, John Dean, Emmanuel Scalais, Mary O’Driscoll, Jenny E. V Morton, Xinguo Hou, Qi Wu, Qingchun Tong, Zhandong Liu, Pengfei Liu, Yong Xu, Zheng Sun
Journal: Nature Neuroscience (2019)
Clonal Evolution of Relapsed CBFB/MYH11 Rearranged Acute Myeloid Leukemia (AML)
Authors: Sabrina Opatz, Sebastian Vosberg, Bianka Ksienzyk, Sebastian Tschuri, Alexander Graf, Stefan Krebs, Helmut Blum, Stephanie Schneider, Martin Neumann, Claudia D. Baldus, Christian Thiede, Jan Moritz Middeke, Friedrich Stoelzel, Stefan K. Bohlander, Karsten Spiekermann, Wolfgang Hiddemann, Klaus H. Metzeler, Philipp A. Greif
Journal: Blood (2018)
Long noncoding <scp>RNA</scp> polymorphisms influence susceptibility to endemic pemphigus foliaceus
Authors: S.C. Lobo‐Alves, D.G. Augusto, W.C.S. Magalhães, E. Tarazona‐Santos, M.F. Lima‐Costa, M.L. Barreto, B.L. Horta, R.C. Almeida, M.L. Petzl‐Erler
Journal: British Journal of Dermatology (2019)

Pemphigus foliaceus (PF) is an epidermal autoimmune disease, characterized by the presence of autoantibodies against the desmosomal protein desmoglein 1. Genetic and environmental factors contribute to PF, a complex disease that is endemic in Brazil and Colombia and neighbouring countries, and in Tunisia. Long noncoding RNAs (lncRNAs) may participate in gene regulation by interacting with DNA, proteins and other RNAs. Dysregulation of lncRNAs has recently been recognized as an important coplayer in the onset or progression of complex diseases. In addition, single-nucleotide polymorphisms (SNPs) located in lncRNA genes have been associated with differential risk to cancer, autoimmunity and infection.Here, we aimed to investigate whether SNPs in lncRNA genes are associated with differential susceptibility to endemic PF.We integrated data from the lncRNA SNP database with genome-wide genotype data obtained for 229 patients and 6681 controls. We tested the association between endemic PF and 2080 SNPs located in lncRNAs applying logistic regression.The most significantly associated SNP was rs7144332 (OR = 1·63, P = 2·8 × 10-6 ), located in the lncRNA gene AL110292·1. Results for five other SNPs were suggestive of association (P < 0·001). In silico analysis indicated that five of the six SNPs impact transcription, three may influence lncRNA's secondary structure, and three may alter microRNA-lncRNA interactions.We showed, for the first time, that variation in lncRNA genes may influence pemphigus pathogenesis. Our findings highlight the importance of lncRNA variation in autoimmune and possibly other complex diseases and suggest polymorphisms for functional validation.
AB0691 Instertitial lung disease and mycroscopic polyangiitis in chilean patients
Authors: P. Wurmann, F. Elgueta, D.E. Vargas, M.L. Molina, K. Vergara, M. Mac-Namara, A. Goecke, H. Gatica, F. Sabugo, S. Saavedra, F. Bozán, J.C. Diaz
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Microscopic Polyangiitis (MPA) is an ANCA associated vasculitis (AAV), associated with p-ANCA (perinuclear) fluorescence pattern and anti- myeloperoxidase (MPO) specificity. Most frequently involved organs are kidney (80%–100%), peripheral nervous system and skin (30%). There is Pulmonary involvement in 25%–35% of patients, being alveolar haemorrhage frequently described. Interstitial lung disease (ILD) has also been recognised. <h3>Objectives</h3> The aim of our study is to report the characteristics of MPA Chilean patients with ILD and to compare it with other series. <h3>Methods</h3> Retrospective study. Patient diagnosed between 2007 and 2016 at the Hospital Clĺnico Universidad de Chile, with ILD, defined as interstitial lung disease on CT scan with Usual Interstitial Pneumonia (UIP) or Non Specific Interstitial Pneumonia (NSIP) pattern, and MPA were included. Demographic, clinical, laboratory and mortality data were plotted. Data from other series were compared with our results. Other causes that could explain the pulmonary involvement were excluded. <h3>Results</h3> From 94 patients with AVV, 36,1% were MPA, being 16 patients with ILD. All were Hispanic, median age 65.3 years,<sup>32–84</sup> female 62,5% (table 1). Common manifestations were constitutional symptoms (100%), weight loss (68,7%) and fever (68,7%). All patients had anaemia, high ESR (mean 84 mm/hr. range 33–120) and CRP (8–22 times above upper normal limit). All patients were ANCA-p and MPO positive. In 10 cases ILD was diagnosed concomitantly with MPA and in 6 was 0.5 to 15 years before. 4 patients developed pulmonary haemorrhage. Images patterns were 10 UIP and 5 NSIP. All patients received corticosteroid as induction therapy, 15 also received cyclophosphamide. One patient plasmapheresis, and one received Rituximab after a relapsed. Azathioprine was used as Maintenance therapy. Four patients died during follow-up. table 2 shows data from other worldwide region compared with our data. <h3>Conclusions</h3> Among chilean patients there are more females, have a more NSIP pattern, and less mortality that other worldwide series. <h3>References</h3> [1] Alba MA, et al. Autoimmun Rev. 2017Jul;16(7):722–729. [2] Flores-Suarez LF, et al. Clin Rheumatol2015;34:1653–4. [3] Fernandez Casares M, et al. Clin Rheumatol2015;34: 1273–7. [4] Huang H, et al. BMC Pulm Med2014;14:8. [5] Kagiyama N, et al. BMJ Open Respir Res. 2015Jan 9;2(1):e000058. [6] Eschun GM, et al. Chest2003;123:297–301. [7] Nada AK, et al. Mayo Clin Proc1990;65:847–56. [8] Comarmond C, et al. Medicine (Baltimore)2014; 93:340–9. [9] Hervier B, et al. Ann Rheum Dis2009;68:404–7. <h3>Disclosure of Interest</h3> None declared
Prognostic Relevance of Medullary Abnormalities in the Appendicular Skeleton Detected By Positron Emission Tomography-Computed Tomography in Patients with Newly Diagnosed Multiple Myeloma
Authors: Yoshiaki Abe, Kentaro Narita, Hiroki Kobayashi, Akihiro Kitadate, Masami Takeuchi, Toshihiro Ouchi, Kosei Matsue
Journal: Blood (2018)
Prolonged Overall Survival (OS) in a Subset of Responders to the Combination of Brentuximab Vedotin (Bv) and Bendamustine (B) in Heavily Treated Patients with Relapsed or Refractory Hodgkin Lymphoma (HL): Results of an International Multi- Center Phase I/II Experience
Authors: Ahmed Sawas, John Kuruvilla, Jennifer Kimberly Lue, Changchun Deng, Jennifer E Amengual, Francesca Montanari, Kerry J Savage, Hager Elgedawe, Diego Villa, Michael Crump, Joseph M Connors, Owen A. O'Connor
Journal: Blood (2018)
SP0126 Big data for treatment effectiveness and safety
Authors: L. Tomlinson
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> While randomised clinical trials remain the gold-standard for examining drug-effects, there are limitations to the evidence they provide. For example, studies are usually too small or too short to detect rare and long-term adverse effects. This is particularly true for kidney-related outcomes where many trials were underpowered to detect outcomes of interest such as end-stage renal disease, too historic to collect data on newly-defined entities such as acute kidney injury or simply excluded patients with chronic kidney disease. In addition, disproportionate recruitment of Caucasian men in mid- to older-life limits the evidence base for understanding risk of adverse-effects in other population groups such as women, the elderly and people of non-Caucasian ethnicity. Determining these outcomes requires long-term surveillance of population databases, usually anonymised health care records, once a drug is in routine use. In this talk I will discuss recent work from our group where we have used routinely collected renal function measurements from primary care to precisely examine kidney-related and other adverse effects. I will discuss some of the difficulties of this approach as well as the potential it offers to understand better the balance between risks and benefits of many drugs in common use. <h3>Disclosure of Interest</h3> None declared
AB0526 Imbalance in elastin-elastase sytem leading to clinical manifestations of systemic lupus erythematosus
Authors: O. Emelyanova, O. Rusanova, I. Gontar, L. Maslakova, N. Emelianov
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> It is believed that in systemic lupus erythematosus antibodies induce a disturbance in the elastin-elastase metabolism, which yields altered soluble isoforms followed by triggering of autoimmunity mechanisms, which damage the elastin-containing tissues. <h3>Objectives</h3> Studying antibody formation in the elastin-elastase system in patients with systemic lupus erythematosus (SLE) using magnetocontrollable adsorbents with an immobilised form of corresponding antigen. <h3>Methods</h3> Sera from 30 donors and 65 SLE patients were studied. Antibodies to elastin and elactase were determined using ELISA test and magnetocontrollable adsorbents with an immobilised form of corresponding antigen. <h3>Results</h3> We analysed changes in the content of antibodies to elastin and elastase in patients with SLE of varying severity assessed using SLAM, SLEDAI scale, and criteria by V.A. Nasonova. The greatest elastin antibody titer was noted in patients with SLE grade III (57.1%, 4 people), with grade II – in 42.5% (17 people), and with grade I – in 33.3% (6 people). The elastin antibody titer in SLE patients being admitted to hospital was reliably higher than in donors (p&lt;0.001). An analysis of the findings showed that patients with vascular lesions demonstrated a significant elevation of elastin antibodies (p&lt;0.05). Besides studying elastin antibodies, we analysed elastase antibodies. Elevated elastase antibodies were revealed in 72.2% of SLE patients with grade I of the condition; in 80.0% with grade II, and in 85.7% of patients with grade III. The titer of elastase antibodies in SLE patients admitted to hospital was reliably higher than in the control group (p&lt;0.01). The highest elastase antibody titer was noted when the skin and joints are affected, and vasculopathy is present. <h3>Conclusions</h3> The regularities revealed by pathogenetic method can be accounted for by considerable B-clonal expansion in SLE patients as the condition progresses. From the point of view of immunology, hyperproduciton of elastin and elastase autoantibodies is noted, which results in autoimmune lesion of the ligamentous apparatus, joints, skin and vessels where this protein is naturally present. <h3>Disclosure of Interest</h3> None declared
SAT0382 Utility of neutrophil cd64 & serum trem-1 in distinguishing bacterial infection from disease flare in sle and anca associated vasculitis
Authors: S. Ajmani, H. Singh, S. Chaturvedi, R. Mishra, M.K. Rai, A. Jain, D.P. Misra, V. Agarwal
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Treating physician is challenged to differentiate between disease activity <i>vs.</i> infection as to the cause of fever in patients with SLE and ANCA associated vasculitis (AAV). Presently, there is no biomarker to reliably differentiate between them. <h3>Objectives</h3> We aimed to determine the usefulness of CD64 (FcγR1) expression on neutrophils and sTREM-1 (soluble triggering receptor expressed on myeloid cells) in serum in distinguishing bacterial infection from disease flare in SLE and AAV. <h3>Methods</h3> 20 healthy controls and patients of SLE and AAV admitted to our unit either with disease flare or bacterial infection were recruited over a period of 1 year. Neutrophil CD64 expression was measured by flow cytometry and sTREM by ELISA from blood samples collected on the day of admission. <h3>Results</h3> Among the 76 patients included in the study 51 (SLE-35 and AAV-16) had disease flare while 25 (SLE-21 and AAV-4) had infection. 72% had fever at presentation. The percentage of neutrophils with CD64 expression and their mean fluorescence intensity in patients with infection were significantly (p&lt;0.05) higher as compared to those without infection and controls (Table-1). The sensitivity and specificity of CD64 expression on neutrophils to diagnose bacterial infection (using a cut off value of 30%) was 85% and 84%, respectively. Whereas, the sensitivity and specificity of procalcitonin was 75% and 85% respectively. There was no significant difference in soluble TREM-1 levels between the two groups. Total leucocyte count (TLC), ESR, CRP, C3, C4 levels were not significantly different between disease flare and infection group. On subgroup analysis (Table-2) patients of SLE with infection had a higher CRP, TLC and Procalcitonin compared to those with disease flare (p&lt;0.5). ROC curves are depicted in figure 1. <h3>Conclusions</h3> CD64 expression on neutrophils is helpful in differentiating bacterial infection from disease flare in patients with SLE and AAV. <h3>Disclosure of Interest</h3> None declared
Assessment of a Bidirectional Association Between Major Depressive Disorder and Alopecia Areata
Authors: Isabelle A. Vallerand, Ryan T. Lewinson, Laurie M. Parsons, Jori Hardin, Richard M. Haber, Mark W. Lowerison, Cheryl Barnabe, Scott B. Patten
Journal: JAMA Dermatology (2019)

<h3>Importance</h3> Alopecia areata (AA) is an autoimmune disease characterized by hair loss that can impose a substantial psychological burden on patients, including major depressive disorder (MDD), yet many patients report mental health symptoms prior to the onset of AA. As such, there may be an association between MDD and AA that acts in both directions. <h3>Objective</h3> To assess the bidirectional association between MDD and AA. <h3>Design, Setting, and Participants</h3> This population-based retrospective cohort study included patients 10 to 90 years of age registered with The Health Improvement Network in general practices in the United Kingdom between January 1, 1986, and May 16, 2012. Statistical analysis was conducted from August 17, 2017, to April 23, 2018. To assess the risk of AA, the following 2 cohorts were defined: patients with an incident diagnosis of MDD (exposure) and a reference general population cohort. To assess the risk of MDD, the following 2 cohorts were defined: patients with an incident diagnosis of AA (exposure) and a reference general population cohort. Person-time was partitioned into unexposed and exposed time in the exposure cohorts. <h3>Main Outcomes and Measures</h3> In the analysis of the risk of AA, development of incident AA during follow-up was considered the main outcome measure. In the analysis of the risk of MDD, development of incident MDD during follow-up was considered the primary outcome measure. <h3>Results</h3> In the analysis of the risk of AA, 405 339 patients who developed MDD (263 916 women and 141 423 men; median age, 36.7 years [interquartile range, 26.6-50.5 years]) and 5 738 596 patients who did not develop MDD (2 912 201 women and 2 826 395 men; median age, 35.8 years [interquartile range, 25.3-52.6 years]) were followed up for 26 years. After adjustment for covariates, MDD was found to increase the risk of subsequently developing AA by 90% (hazard ratio, 1.90; 95% CI, 1.67-2.15;<i>P</i> &lt; .001). Antidepressants demonstrated a protective effect on the risk of AA (hazard ratio, 0.57; 95% CI, 0.53-0.62;<i>P</i> &lt; .001). In the analysis of the risk of MDD, 6861 patients who developed AA (3846 women and 3015 men; median age, 31.5 years [interquartile range, 18.2 years]) and 6 137 342 patients who did not develop AA (3 172 371 women and 2 964 971 men; median age, 35.9 years [interquartile range, 27.0 years]) were followed up for 26 years. After adjustment for covariates, AA was found to increase the risk of subsequently developing MDD by 34% (hazard ratio, 1.34; 95% CI, 1.23-1.46;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> These temporal analyses suggest that, while patients with AA are at risk for subsequently developing MDD, having MDD also appears to be a significant risk factor for development of AA, with antidepressant use confounding this risk.