tbuckley/cabot-search huggingface dataset:
FRI0164 Anti-pfdn5 antibody as a biomarker for uveitis in ankylosing spondylitis
Authors: O.C. Kwon, E.-J. Lee, E.-J. Chang, W.J. Seo, J.S. Oh, S. Hong, C.-K. Lee, B. Yoo, Y.-G. Kim
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Noninfectious uveitis is the most common extra-articular manifestation of ankylosing spondylitis (AS). However, molecules related to the disease pathogenesis have yet to be identified, and no biomarkers are available for uveitis in AS. <h3>Objectives</h3> We aimed to identify the biomarkers for uveitis in AS, and elucidate the possible pathogenesis of uveitis in AS associated with the identified biomarkers. <h3>Methods</h3> Protein microarray using ProtoArray was performed to profile autoantibodies present in sera from patients with various autoimmune diseases, including eight AS patients with uveitis. The autoantibodies with higher reactivity in AS patients with uveitis compared with other patients were selected, and the levels of autoantibodies were measured using ELISA in the sera from AS patients with (n=32) or without uveitis history (n=32), patients with rheumatoid arthritis (n=20) and from healthy individuals (n=12). To evaluate the involvement of target antigen in pathogenesis of spondyloarthritis-related uveitis, we conducted an <i>in vivo</i> study using curdlan-induced SKG mice, which spontaneously develops arthritis as well as uveitis, and an <i>in vitro</i> study using retinal pigment epithelium cell-line (RPE19). <h3>Results</h3> 4 antibodies (Abs) were selected as a candidate for biomarker (anti-PFDN5, area under curve [AUC]=1.00; anti-serine threonine protein kinase 24 Ab, AUC=0.906; anti-odontogenic ameloblast associated protein Ab, AUC=0.859; anti-protocadherin alpha C2 Ab, AUC=0.859). In ELISA, anti-PFDN5 Abs was significantly elevated in AS patients with uveitis compared to AS patients without uveitis. Ocular histology showed that compared to PBS-treated SKG mice, SKG mice with uveitis had strong expression of PFDN5 in iris, ciliary body, and retina. PERK and peIF2α, which are ER stress related proteins, were downregulated in PFDN5 siRNA-treated RPE19 cells in tunicamycin-induced condition, suggesting that PFDN5 enhances ER stress via PERK and peIF2α pathway. <h3>Conclusions</h3> We identified anti-PFDN5 antibody as a putative biomarker for uveitis in AS. PFDN5 was increased in ocular lesion, which may be associated with disease pathogenesis. <h3>Acknowledgements</h3> None. <h3>Disclosure of Interest</h3> None declared
Abstract MP59: The Association Between Acute Mental Stress and Abnormal P-wave Axis
Authors: Zakaria Almuwaqqat, Wesley T O'Neal, Muhammad Hammadah, Pratik Sandesara, Belal Kaseer, Matthew Amin, Ayman S Tahhan, Mohamad M Gafeer, Naser Abdelhadi, Malik Obideen, Ibhar Al Mheid, Ayman Alkhoder, Douglas Bremner, Michael Kutner, Elsayed Z Soliman, Amit J Shah, Arshed A Quyyumi, Viola Vaccarino
Journal: Circulation (2018)

Background: Exposure to psychological stress has been associated with the development of sustained arrhythmias. Acute changes in atrial electrophysiology may serve as intermediate phenotypes for stress-induced arrhythmia. The relationship between atrial electrical changes and stress related changes in heart rate and myocardial ischemia is unknown. We sought to study the effect of altered atrial electrophysiology and stress related rise in HR and myocardial ischemia in females and males. Methods: We examined if acute mental stress was associated with abnormal P-wave axis development in 359 patients (mean age=56 ± 9.9 years; 62% men; 43% white) with stable coronary heart disease and normal baseline P-wave axis (between 0° and 75°) who underwent mental stress testing (speech task). We computed the percentage of patients who had abnormal P-wave axis during stress and recovery. Sex-stratified analyses were performed. A multivariable logistic regression model was used to determine if mental stress ischemia independent predictors of abnormal P-wave axis development. Results: A total of 46 (13%) patients developed abnormal P-wave axis during either stress or recovery (stress: n=43, 12%; recovery: n=12, 3%). A rise in heart rate during mental stress was associated with an increased risk of abnormal P-wave axis development (per 5-unit increase: OR=1.37, 95%CI=1.03, 1.30). Mental stress-induced myocardial ischemia was associated with increased risk of abnormal P-wave axis in women (OR=5.2, 95%CI=1.7, 15.6) and not in men (OR=0.1, 95%CI=0.01, 1.01), p-interaction=0.004). Interactions were not detected for other characteristics. Conclusion: Acute mental stress results in the development of abnormal P-wave axis, and this phenomenon is related to increases in heart rate and, among women, mental stress-induced ischemia. Our data suggest that acute psychological stress can promote adverse transient electrical changes in the atria.
Gamma tocopherol effect on LPS-induced sputum neutrophilia is not modified by BMI or GSTM1 genotype
Authors: Amika K. Sood, Allison J. Burbank, Charity G. Duran, Kimberly Enders, Haibo Zhou, David B. Peden, Michelle L. Hernandez
Journal: Journal of Allergy and Clinical Immunology (2019)
Prolyl Hydroxylase 3 (Phd3) Is a Therapeutic Target in Isocitrate Dehydrogenase 1 (IDH1) Mutated Acute Myeloid Leukemia
Authors: Anuhar Chaturvedi, Michelle Maria Araujo Cruz, Ramya Goparaju, Razif Gabdoulline, Renate Schottmann, Kerstin Görlich, Arnold Kloos, Felicitas Thol, Robert Geffers, Dimitrios Mougiakakos, Peter Carmeliet, Arnold Ganser, Michael Heuser
Journal: Blood (2018)
Clinical Validation of Treatment Response Predictions Using a Genomics Driven Computational Biology Modelling Multiple Myeloma Algorithm
Authors: Ravi Vij, Justin King, Mark A. Fiala, Neeraj Kumar Singh, Mohammed Sauban, Zakir Husain, Anjanasree V Lakshminarayana, Anay Ashok Talawdekar, Upasana Mitra, Taher Abbasi, Shireen Vali
Journal: Blood (2018)
Estimating the Burden of Hospital-Acquired Venous Thromboembolism: The Argument for Implementation of Mandatory Risk Reduction Strategies
Authors: Barry Kevane, Mary Day, Noirin Bannon, Leo Lawler, Tomas Breslin, Claire Andrews, Howard Johnson, Michael Fitzpatrick, Karen Murphy, Olivia Mason, Sarah Kelliher, Annemarie O'Neill, Fionnuala Donohue, Fionnuala Ni Ainle
Journal: Blood (2018)
Establishing Baseline Cervical Cancer Screening Coverage — India, 2015–2016
Authors: Elizabeth A. Van Dyne, Benjamin D. Hallowell, Mona Saraiya, Virginia Senkomago, Shivani A. Patel, Sutapa Agrawal, Arpita Ghosh, Deepika Saraf, Ravi Mehrotra, Preet K. Dhillon
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Cervical cancer is the second leading cause of new cancer cases and cancer-related deaths among women in India, with an estimated 96,922 new cases and 60,078 deaths each year.* Despite the availability of effective low-cost screening options in India, limited access to screening and treatment services, diagnosis at a later stage, and low investment in health care infrastructure all contribute to the high number of deaths (1). In 2016 the Ministry of Health and Family Welfare of India recommended cervical cancer screening using visual inspection with acetic acid every 5 years for women aged 30-65 years (per World Health Organization [WHO] guidelines) (2,3). To establish a baseline for cervical cancer screening coverage, survey data were analyzed to estimate the percentage of women aged 30-49 years who had ever been screened for cervical cancer (defined as ever having had a cervix examination). Cervical cancer screening was estimated using data from the Fourth National Family Health Survey† (NFHS-4), a nationally representative survey conducted at the district level during 2015-2016, which included 699,686 Indian women aged 15-49 years. Lifetime cervical cancer screening prevalence was low (29.8%) and varied by geographic region, ranging from 10.0% in the Northeast Region to 45.2% in the Western Region. Prevalence of screening was higher among women with higher levels of education and household wealth, those who had ever been married, and urban residents. This screening prevalence can be used as a baseline indicator for cervical cancer screening in India in accordance with the WHO Noncommunicable Diseases Global Monitoring Framework during state-based programmatic rollout and program evaluation (4).
Prognosis and Neuropathologic Correlation of Clinical Subtypes of Parkinson Disease
Authors: Eduardo De Pablo-Fernández, Andrew J. Lees, Janice L. Holton, Thomas T. Warner
Journal: JAMA Neurology (2019)

<h3>Importance</h3> Clinical subtyping of Parkinson disease at diagnosis is useful in estimating disease course and survival. Severity and rate of progression of neuropathologies are important determinants of clinical Parkinson subtypes. <h3>Objective</h3> To provide longitudinal clinical disease-course data and neuropathologic correlation for newly proposed Parkinson disease subtypes. <h3>Design, Setting, and Participants</h3> Retrospective cohort study of consecutive patients with autopsy-confirmed Parkinson disease who were regularly seen throughout their disease course by hospital specialists in the United Kingdom and donated their brain at death to the Queen Square Brain Bank between January 2009 and December 2017. Patients with additional neuropathologic diagnoses, monogenic forms of parkinsonism, or insufficiently detailed clinical information were excluded. Based on severity of motor symptoms, rapid eye movement sleep behavior disorder, and autonomic and cognitive function at diagnosis, patients were classified adapting a subtyping classification into mild-motor predominant, intermediate, or diffuse malignant subtypes. <h3>Main Outcomes and Measures</h3> Time from diagnosis to disease milestones (recurrent falls, wheelchair dependence, dementia, and care home placement) and death were compared between subtypes, and their risk was estimated using Cox hazard regression models. Severity and distribution of Lewy pathology and Alzheimer disease–related pathology were assessed using staging systems. <h3>Results</h3> From a total of 146 patients, 111 patients were included (67 men [60.4%]; mean [SD] age at diagnosis, 62.5 [11.5] years). The diffuse malignant subtype had earlier development of milestones and reduced survival. Cox proportional hazard regression showed an increased adjusted risk of any disease milestone (hazard ratio, 10.90; 95% CI, 5.51-21.58;<i>P</i> &lt; .001) and death (hazard ratio, 3.65; 95% CI, 1.98-6.75;<i>P</i> &lt; .001) in the diffuse malignant group. Age at diagnosis was the only additional variable with statistical significance (adjusted hazard ratio for death, 1.14; 95% CI, 1.11-1.17;<i>P</i>&lt;.001). Staging of Lewy pathology and Alzheimer disease–related pathology did not differ between subtypes, although they showed different rates of progression, and the latter was associated with age at death. <h3>Conclusions and Relevance</h3> Parkinson clinical subtypes at diagnosis may estimate disease course and survival, which may be useful in providing a more accurate prognosis in individual patients in clinical practice and helping to stratify subgroups in clinical trials. Different severity and progression of neuropathologies are important determinants of Parkinson subtypes, and age at diagnosis should be included in future subtype classifications.
Diffuse Large B-Cell Lymphoma Remodels the Fibroblastic Reticular Network That Acquires Aberrant Immunosuppressive Capabilities; Implications for the Regulation of Anti-Tumor Immunity in the Immuno-Oncology Era
Authors: Benedetta Apollonio, Peter Jarvis, Beth Phillips, Andrea Kuhnl, Jon Salisbury, Georgios Zacharioudakis, Lesley-Ann Sutton, Richard Rosenquist, Ruth Jarrett, Rose-Marie Amini, Anna Vardi, Alan G. Ramsay
Journal: Blood (2018)
SAT0377 The burden of monosodium urate crystals assessed by dual-energy ct and ultrasonography is not correlated to cardiovascular risk
Authors: T. Pascart, B. Capon, A. Grandjean, J. Legrand, N. Namane, E. Houvenagel, L. Norberciak, J.-F. Budzik
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Gout is associated with higher cardiovascular risk and increases with disease severity. It is not clear if the monosodium urate (MSU) crystal burden is associated with traditional cardiovascular risk factors. <h3>Objectives</h3> The objective of this study was to explore the relationship between the extent of MSU deposition assessed with ultrasonography (US) and dual-energy CT (DECT) and cardiovascular risk. <h3>Methods</h3> Gout patients naive of urate lowering therapy were included in this cross-sectional study to undergo DECT scans for the assessment of total MSU volume deposition of the knees and feet, and US to evaluate the number of joints with the double contour (DC) sign among the femoro-patellar, talo-crural and first metatarsophalangeal joints. Participants were screened for traditional cardiovascular risk factors and levels of the ACC/AHA 10 year-risk for heart disease or stroke was calculated. The primary endpoint was the Spearman correlation coefficient ρ between DECT MSU volume and cardiovascular risk. <h3>Results</h3> A total of 50 patients predominantly male (46/50) aged 62.6 years (±14.1) were included. Participants had gout duration of 9.5 years (±11.8), had experienced 4.1 flares (±6.3) over the past year, had serum urate (SU) levels of 8.1 mg/dL (±2.3), and 35/50 had at least one US tophus of 1.5 cm3 (±1.8). The volume of MSU deposits with DECT was 3.9 cm3 (±11.2) for the feet and 2 cm3 (±4.4) for the knees. Overall, 28 patients presented with the metabolic syndrome. Correlations between DECT volumes of MSU deposits of the knees, feet, and knees+feet were poor with ρ respectively of 0.23, 0.03 and 0.21. The was no correlation between the number of joints with the DC sign and cardiovascular risk (ρ of 0) and the correlation was poor with SU levels (ρ=0.09). Patients with the metabolic syndrome had similar DECT volume of MSU deposits than those without (p=0,29). <h3>Conclusions</h3> This study suggests that the association of gout with traditional cardiovascular risk factors is not related to the extent of the monosodium urate crystal burden. <h3>Disclosure of Interest</h3> None declared
Selenium disrupts androgen receptor and estrogen receptor signaling in prostate and breast cancer cells
Authors: Soo Lee, Nagalakshmi Nadiminty, Wei Lou, Allen C. Gao
Journal: Cancer Research (2005)

2446  A previous controlled intervention trial showed that selenium supplementation was effective in reducing the incidence of cancers including prostate. Physiological concentrations of selenium have also been reported to inhibit the growth of human prostate cancer cells in vitro. Since androgen receptor (AR) signaling plays a critical role in the development and progression of prostate cancer, we examined the effects of selenium on AR expression and activation. Selenium was able to significantly down-regulate the expression of PSA transcript and protein within hours in the androgen-responsive LNCaP cells. Decreases in androgen receptor (AR) transcript and protein followed a similar dose and time response pattern upon exposure to selenium. Selenium inhibited the trans-activating activity of AR in cells transfected with the wild type AR expression vector. Selenium also suppressed the binding of AR to the ARE site. Taken together, in view of the fact that activation of AR signaling plays important roles during prostate cancer progression, an important implication of this study is that a selenium intervention strategy aimed at toning down the amplitude of androgen signaling could be benefit for controlling morbidity of prostate cancer. We also found that selenium decreased the levels of expression of estrogen receptor (ER-α) mRNA and protein and reduced the binding of labeled estradiol to ER in human breast MCF-7 cells. Selenium inhibited the trans-activating activity of ER in MCF-7 cells expressing functional ER using a luciferase reporter construct linked to estrogen responsive element. Selenium decreased the binding of ER to the estrogen responsive element site. Selenium suppressed estrogen induction of the endogenous target gene c-myc. In contrast to the effect on ER-α in MCF-7 cells, selenium increased ER-β mRNA expression in MDA-MB231 human breast cancer cells. Thus, differential regulation of ERα and ERβ in breast cancer cells may represent a novel mechanism of selenium action and provide a rationale for selenium breast cancer prevention trial.
Retinoic Acid Receptor Alpha Represses a Th9 Transcriptional and Epigenomic Program to Reduce Allergic Pathology
Authors: Daniella M. Schwartz, Taylor K. Farley, Nathan Richoz, Chen Yao, Han-Yu Shih, Franziska Petermann, Yuan Zhang, Hong-Wei Sun, Erika Hayes, Yohei Mikami, Kan Jiang, Fred P. Davis, Yuka Kanno, Joshua D. Milner, Richard Siegel, Arian Laurence, Françoise Meylan, John J. O’Shea
Journal: Immunity (2019)
Abstract 14288: Effect of Pre-Stroke Body Mass Index on Post-Stroke Mortality in the United States Veteran Population
Authors: Lauren Costa, Laura Tarko, Yuk-Lam Ho, Daniel Posner, Serkalem Demissie, David R Gagnon, Kello Cho, Luc Djousse, Sudha Seshadri, Peter W Wilson, Hugo J Aparicio
Journal: Circulation (2018)

Introduction: Previous studies relating weight to post-stroke mortality have shown conflicting results, with some showing lower risk of mortality among overweight or obese individuals. We studied t...
AB0794 Myositis damage index in a miositis population cohort
Authors: O. Enriquez, A. Lilia, I. Fedra
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Idiopathic inflammatory myopathies (IIM) are a heterogeneous and uncommon group of diseases characterised by muscular involvement and many systemic manifestations. They usually have a chronic course, and despite treatment they often develop functional impairment. MDI-MYODAM a score to assess damage has been recently developed. Few publications in this regard have reported a prevalence of 92%. There are no studies in Mexican-mestizo population describing the extent of damage and its main determinants. <h3>Objectives</h3> To investigate the prevalence of damage measured with the MDI-MYODAM tool in patients with IIM and its relationship with characteristics of the disease and treatment <h3>Methods</h3> A cross-sectional study was conducted in an IIM cohort from a national reference hospital. MDI questionnaire was applied to all patients. Demographic, disease characteristics, IIM subgroup (dermatomyositis, polymyositis and overlap), comorbidities (Charlson index), medical treatment were collected. Descriptive statistics were applied. Bivariate Pearson correlation test was conducted to analyse associations between MDI score and clinical characteristics. P value&lt;0.05 was considered as a statistically significant. <h3>Results</h3> Fifty subjects participated, 75% were women, mean age at diagnosis was 40.7 years (SD±) and mean duration of the disease was 11.8±8.3 years. Thirthy-one percent of patients had polymyositis, 31% dermatomyositis, 12% juvenile dermatomyositis, 10% overlap myositis (mainly systemic lupus erythematosus, scleroderma and rheumatoid arthritis). The mean Charlson index was 2.7±2.4. Eighty-one percent had a score greater than 0 for at least one category; majority within the endocrinological systems (55%), skeletal (51%), gastrointestinal (35%). The mean total damage score (MDI) was 3.6±2.9. The mean score for the total damage according to the MYODAM score was 6.9±5.1. A moderate correlation between the MDI score and the use of glucocorticoids (r 0.3, CI 95% 0.1–0.6, p&lt;0.01). No associations between damage and activity of the disease or IIM subgroup were observed. <h3>Conclusions</h3> Most patients with IIM develop some kind of damage, with greater impact on the endocrinological, skeletal and gastrointestinal systems. There increases with the time of evolution and the use of steroids in a non-linear way. Therefore, these results should be taken into account in the decision-making process in long-term treatment. <h3>References</h3> [1] Sultan, SM, et al. Interrater reliability and aspects of validity of the myositis damage index. Ann Rheum Dis2011;70:1272–76. [2] Clarke AE, et al. A longitudinal study of functional disability in a national cohort of patients with polymyositis/dermatomyositis. Arthritis Rheum1995;38:1218–24. [3] Bellutti EF, et al. Development of validated disease activity and damage indices for the juvenile idiopathic inflammatory myopathies II. Arthritis Rheum1999; 42:2213–19. <h3>Disclosure of Interest</h3> None declared
Ankie Borgstein van Wijk
Authors: Johannes Borgstein
Journal: BMJ (2019)

Ankie Borgstein van Wijk lived on to just beyond the age of 93 and dedicated at least 60 years of her life to paediatrics and her small farm just outside Blantyre in Malawi.

Born in 1925, the only child of an eminent citizen from Gouda, Netherlands, she grew up a solitary child, rarely accompanying her parents on holiday, being sent instead to various summer camps. After high school she went on to study medicine in Utrecht, starting just before the second world war. During the war some of the lectures continued clandestinely, and she had to sit for exams at the professors’ homes.

Meanwhile she worked for the resistance, ferrying messages concealed under the saddle of her bicycle between various resistance cells. Had these been discovered she would have been summarily executed. Her father meanwhile spent several years during the war as a German hostage, incarcerated in the local jail. Ten hostages were randomly selected and executed for every German soldier killed by the resistance, so her resistance work must have occasioned a great deal of soul searching

After the end of the war she met Jan, a fellow medical student, who was to become her husband and the love of her life. She never fully recovered from his untimely death at the age of 52, although she outlived him by 39 years.

They were married in 1951 and made plans both for a large family (seven sons in the space of nine years), and to move out of Europe. Chile as a first choice was discarded owing to administrative restrictions, and their interest turned towards Africa. In early1960, having finished his surgical training, Jan requested an appointment with the undersecretary for colonial affairs in London. The Foreign Office must have assumed he was a representative of the Dutch government, …
CRISPR/Cas9-Generated Models Uncover Therapeutic Vulnerabilities of Del(11q) Chronic Lymphocytic Leukemia Cells to Dual BCR and PARP Inhibition
Authors: Miguel Quijada Álamo, María Hernández-Sánchez, José Luis Ordóñez, Verónica Alonso Pérez, Ana E. Rodriguez, Ignacio García-Tuñón, Ana B Herrero, Laura San-Segundo, Michaela Gruber, Juan Luis García, Rocio Benito, Catherine J. Wu, Jesús-María Hernández-Rivas
Journal: Blood (2018)