tbuckley/cabot-search huggingface dataset:
SAT0563 Identification and validation of physical activity phenotypes for knee osteoarthritis: a population-based cohort study
Authors: I.P. Munugoda, F. Pan, K. Wills, F. Cicuttini, S.E. Graves, M. Lorimer, G. Jones, M.L. Callisaya, D. Aitken
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The identification of phenotypes to reduce heterogeneity of characteristics is important in understanding the development and progression of knee osteoarthritis. <h3>Objectives</h3> This study aimed to identify physical activity (PA) phenotypes and to investigate the association of these phenotypes with tibial cartilage volume, bone marrow lesions (BMLs) and knee replacements (KR) over 10.7 years. <h3>Methods</h3> 1046 community-dwelling older adults aged 50–80 years were studied. At baseline, PA was measured by pedometers (steps/day), knee pain was assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and body mass index (BMI) was determined utilising objective weight and height measures. MRI scans were conducted at baseline and 10.7 years to assess tibial cartilage volume and BMLs. The incidence of KR was determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. Latent class analysis was used to determine 'PA phenotypes' based on PA, BMI and WOMAC pain at baseline. Linear mixed-effects models and log-binomial models were used to estimate the associations between the identified PA phenotypes with change in cartilage volume, incident BMLs, and KR surgery over 10.7 years. All models were adjusted for age, sex, and history of knee injury or surgery, while the KR model was additionally adjusted for the prevalence of knee radiographic osteoarthritis. <h3>Results</h3> Three PA phenotypes were identified: Class 1: Normal/overweight participants with low levels of PA and low pain (42%); Class 2: Obese participants with low levels of PA and high pain (26%); Class 3: Normal/overweight participants with high levels of PA and low pain (32%). Mean cartilage volume loss over 10.7 years was 465±231 mm<sup>3</sup>. 221 participants had an incident BML while 74 had an incident KR. Class 2 participants had greater cartilage volume loss over 10.7 years (Beta: −79.9, 95% CI −135.8,–23.9) and, had a higher risk of KR (RR 2.36, 95% CI 1.20, 4.67) compared to Class 1 participants. Class 3 was not associated with cartilage volume loss (Beta: −36.2, 95% CI −86.6, 14.1) or risk of KR (RR 0.86, 95% CI 0.40, 1.84) compared to Class 1. Similarly, PA phenotypes were not associated with incident BMLs (Class 2: RR 1.15, 95% CI 0.88, 1.50; Class 3: RR 1.19, 95% CI 0.93, 1.54; compared to Class 1). <h3>Conclusions</h3> Our findings support the existence of homogeneous PA profiles, and suggest that PA interacts with body weight and knee pain and has long-term impacts on osteoarthritis outcomes. <h3>Disclosure of Interest</h3> None declared
Better cancer-specific survival in young patients with nonmetastatic intrahepatic cholangiocarcinoma: A retrospective study of SEER database.
Authors: Zheng Wang, Lunxiu Qin
Journal: Journal of Clinical Oncology (2017)

e15637 Background: Intrahepatic cholangiocarcinoma (ICC) is a complicated and fatal malignancy. Aging plays a significant role in the occurrence and development of this liver cancer, but its prognostic role remains unclear. The purpose of this study is to compare the cancer specific survival (CSS) in young patients with elderly ones, and to further establish a nomogram, integrating age and other risk factors, to predict survival outcomes in ICC patients. Methods: Cases of intrahepatic cholangiocarcinoma diagnosed between 2004 and 2013 were extracted from SEER database. Patients were excluded if they had incomplete TNM staging, with distant metastasis (M1) or no evaluation on lymph node. The enrolled cases were divided into young (under 50 years of age) and elderly groups (50 years and over). 1-year and 3-year cancer CSS data were obtained. Kaplan-Meier methods were adopted and multivariable Cox regression models were built for the analysis of survival outcomes and risk factors. A predictive nomogram for prognosis was generated by software R, and the performance of the nomogram was assessed by C-index and validation curves. Results: There were 2385 patients meeting inclusion criteria with median follow up of 17.0 months. Compared with elderly group, young patients showed significantly higher pathological grading (P = 0.006), lower rate of lymph node invasion (P = 0.002), and early TNM stage (P = 0.005). The 1-year and 3-year CSS rates were 57.3% and 19.2% in young group, and 38.2% and 10.8% in elderly group. Both univariate analysis (P = 0.019) and multivariate analysis (P = 0.040) indicated significant difference of CSS between the two groups. The multi-factor, integrative nomogram was established to predict prognosis, whose predictive power was higher than the conventional tumor staging (AJCC 7 th edition staging). And the calibration curves for the probability of 1- and 3-year CSS indicated that the nomogram-based prediction was in optimal agreement with actual observed survival. Conclusions: Compared with elderly patients, young patients with non-metastatic ICC appear to have more favorable clinicopathological characteristics and better prognosis.
Macrophage Rac2 Is Required to Reduce the Severity of Cigarette Smoke–induced Pneumonia
Authors: Jennifer L. Larson-Casey, Linlin Gu, Patricia L. Jackson, David E. Briles, Joanetha Y. Hale, J. Edwin Blalock, J. Michael Wells, Jessy S. Deshane, Yong Wang, Dana Davis, Veena B. Antony, Adriana V. F. Massicano, Suzanne E. Lapi, A. Brent Carter
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Cigarette smoking is prevalent in the United States and is the leading cause of preventable diseases. A prominent complication of smoking is an increase in lower respiratory tract infections (LRTIs). Although LRTIs are known to be increased in subjects that smoke, the mechanism(s) by which this occurs is poorly understood.Determine how cigarette smoke (CS) reduces reactive oxygen species (ROS) production by the phagocytic NOX2 (NADPH oxidase 2), which is essential for innate immunity in lung macrophages.NOX2-derived ROS and Rac2 (Ras-related C3 botulinum toxin substrate 2) activity were determined in BAL cells from wild-type and Rac2-/- mice exposed to CS or cadmium and in BAL cells from subjects that smoke. Host defense to respiratory pathogens was analyzed in mice infected with Streptococcus pneumoniae.NOX2-derived ROS in BAL cells was reduced in mice exposed to CS via inhibition of the small GTPase Rac2. These mice had greater bacterial burden and increased mortality compared with air-exposed mice. BAL fluid from CS-exposed mice had increased levels of cadmium, which mediated the effect on Rac2. Similar observations were seen in human subjects that smoke. To support the importance of Rac2 in the macrophage immune response, overexpression of constitutively active Rac2 by lentiviral administration increased NOX2-derived ROS, decreased bacterial burden in lung tissue, and increased survival compared with CS-exposed control mice.These observations suggest that therapies to maintain Rac2 activity in lung macrophages restore host defense against respiratory pathogens and diminish the prevalence of LRTIs in subjects that smoke.
Transethnic, Genome-Wide Analysis Reveals Immune-Related Risk Alleles and Phenotypic Correlates in Pediatric Steroid-Sensitive Nephrotic Syndrome
Authors: Hanna Debiec, Claire Dossier, Eric Letouzé, Christopher E. Gillies, Marina Vivarelli, Rosemary K. Putler, Elisabet Ars, Evelyne Jacqz-Aigrain, Valery Elie, Manuela Colucci, Stéphanie Debette, Philippe Amouyel, Siham C. Elalaoui, Abdelaziz Sefiani, Valérie Dubois, Tabassome Simon, Matthias Kretzler, Jose Ballarin, Francesco Emma, Matthew G. Sampson, Georges Deschênes, Pierre Ronco
Journal: Journal of the American Society of Nephrology (2018)

Background Steroid-sensitive nephrotic syndrome (SSNS) is a childhood disease with unclear pathophysiology and genetic architecture. We investigated the genomic basis of SSNS in children recruited in Europe and the biopsy-based North American NEPTUNE cohort. Methods We performed three ancestry-matched, genome-wide association studies (GWAS) in 273 children with NS (Children Cohort Nephrosis and Virus [NEPHROVIR] cohort: 132 European, 56 African, and 85 Maghrebian) followed by independent replication in 112 European children, transethnic meta-analysis, and conditional analysis. GWAS alleles were used to perform glomerular cis -expression quantitative trait loci studies in 39 children in the NEPTUNE cohort and epidemiologic studies in GWAS and NEPTUNE (97 children) cohorts. Results Transethnic meta-analysis identified one SSNS-associated single-nucleotide polymorphism (SNP) rs1063348 in the 3′ untranslated region of HLA-DQB1 ( P =9.3×10 −23 ). Conditional analysis identified two additional independent risk alleles upstream of HLA-DRB1 (rs28366266, P =3.7×10 −11 ) and in the 3′ untranslated region of BTNL2 (rs9348883, P =9.4×10 −7 ) within introns of HCG23 and LOC101929163 . These three risk alleles were independent of the risk haplotype DRB1*07:01-DQA1*02:01-DQB1*02:02 identified in European patients. Increased burden of risk alleles across independent loci was associated with higher odds of SSNS. Increased burden of risk alleles across independent loci was associated with higher odds of SSNS, with younger age of onset across all cohorts, and with increased odds of complete remission across histologies in NEPTUNE children. rs1063348 associated with decreased glomerular expression of HLA-DRB1, HLA-DRB5, and HLA-DQB1. Conclusions Transethnic GWAS empowered discovery of three independent risk SNPs for pediatric SSNS. Characterization of these SNPs provide an entry for understanding immune dysregulation in NS and introducing a genomically defined classification.
Producing anti-inflammatory macrophages by nanoparticle-triggered clustering of mannose receptors
Authors: Jingjing Gan, Yunyan Dou, Yurong Li, Zhenzhen Wang, Lintao Wang, Shang Liu, Qiu Li, Heran Yu, Chunyan Liu, Congwei Han, Zhen Huang, Junfeng Zhang, Chunming Wang, Lei Dong
Journal: Biomaterials (2018)
Lipid Nanoparticle-Delivered Chemically Modified mRNA Restores Chloride Secretion in Cystic Fibrosis
Authors: Ema Robinson, Kelvin D. MacDonald, Kai Slaughter, Madison McKinney, Siddharth Patel, Conroy Sun, Gaurav Sahay
Journal: Molecular Therapy (2018)

The promise of gene therapy for the treatment of cystic fibrosis has yet to be fully clinically realized despite years of effort toward correcting the underlying genetic defect in the cystic fibrosis transmembrane conductance regulator (CFTR). mRNA therapy via nanoparticle delivery represents a powerful technology for the transfer of genetic material to cells with large, widespread populations, such as airway epithelia. We deployed a clinically relevant lipid-based nanoparticle (LNP) for packaging and delivery of large chemically modified CFTR mRNA (cmCFTR) to patient-derived bronchial epithelial cells, resulting in an increase in membrane-localized CFTR and rescue of its primary function as a chloride channel. Furthermore, nasal application of LNP-cmCFTR restored CFTR-mediated chloride secretion to conductive airway epithelia in CFTR knockout mice for at least 14 days. On day 3 post-transfection, CFTR activity peaked, recovering up to 55% of the net chloride efflux characteristic of healthy mice. This magnitude of response is superior to liposomal CFTR DNA delivery and is comparable with outcomes observed in the currently approved drug ivacaftor. LNP-cmRNA-based systems represent a powerful platform technology for correction of cystic fibrosis and other monogenic disorders.
AB0538 Increased body mass index may not be a risk factor for the development of lupus nephritis
Authors: Y.P. Chock, A. Danve, M. Petri, W. Fu
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Studies have indicated that elevated body mass index (BMI) increases risk of Chronic Kidney Disease (CKD). Obesity is a low grade inflammatory state which leads to CKD by glomerulosclerosis. Systemic Lupus Erythematosus (SLE) is associated with high leptin levels and dyslipidemia. We hypothesised that obese SLE patients may be at increased risk of nephritis. <h3>Objectives</h3> We studied BMI as possible predictor for development of lupus nephritis (LN) in SLE. <h3>Methods</h3> We performed a retrospective cross sectional study on a longitudinal lupus cohort. Patients were enrolled from year 1987 to 2015. We compared demographics, clinical information, labs between patients with and without LN (table 1) and between patients with SLE with and without obesity. Mean and standard deviations were reported for continuous variables. Number and percentages were shown for categorical variables and chi-square test was utilised for comparison. T- test was used to compare patients between the groups. <h3>Results</h3> Total of 1362 patients with SLE fulfilling revised ACR criteria were included; 60.9% were Caucasian and 32.8% African American. 596 had biopsy-proven LN however 524 patients were excluded because they had proteinuria before or at cohort entry. Only first available BMI were analysed: 32.7% were obese (BMI &gt;30 kg/m<sup>2</sup>), 27.2% overweight (BMI: 25–29.9 kg/m<sup>2</sup>), 37.5% normal (BMI: 18.5–24.9 kg/m<sup>2</sup>) and 2.6% underweight (BMI &lt;18.5 kg/m<sup>2</sup>). 39.4% (537) patients were on steroids at first BMI measurement. Results are described in table 1. BMI measured as continuous (p=0.51) and categorical variables (overweight p=0.64, obese p=0.67) were not associated with LN after adjusting for age, sex and ethnicity. SLE patients with obesity were found to have lower disease activity (SLEDAI), proteinuria, dsDNA titers and higher complement levels. <h3>Conclusions</h3> Obesity was not associated with the development of lupus nephritis. Obese patients with SLE had lower disease activity as measured by SLEDAI, dsDNA titers and complement levels. <h3>Disclosure of Interest</h3> None declared
US suicide rate is climbing steadily with highest prevalence in sparsely populated western states
Authors: Owen Dyer
Journal: BMJ (2018)

The suicide rate in the United States has risen 1.5% a year since 1999, according to data released by the Centers for Disease Control and Prevention (CDC). If this rate of increase continues, by 2050 the US suicide rate would be more than double what it was at the beginning of the century.

The rise has been significant nationally and in 44 of 50 states. In 25 states, the suicide rate rose more than 30% between 1999 and 2016, the CDC reported in its Morbidity and Mortality Weekly Report .1

The period from 2001 to 2016 also saw a 42% increase in the rate of emergency department visits for non-fatal self harm, the CDC found.

There was great …
B형 간염 바이러스에 의한 비대상성 간경변증 환자에서 라미부딘의 치료 효과
Authors: 정세라, 서동진, 박현주, 박영환, 송희곤, 이한주, 정영화, 이영상
Journal: Clinical and Molecular Hepatology (2002)

목적: 최근 라미부딘이 B형 간염 바이러스와 연관된 비대상성 간경변증 환자에서도 효과적이라고 보고되었으나, 대부분의 경우에서 간이식을 병용하였거나 6개월 이상 치료한 환자만을 대상으로 하였다는 문제점이 있다. 이번 연구에서는 이러한 문제점을 극복하기 위하여 라미부딘 치료를 받은 비대상성 간경변증 환자를 ...
Outbreak of <i>E. coli</i> O157:H7 Infections Associated with Exposure to Animal Manure in a Rural Community — Arizona and Utah, June–July 2017
Authors: Sarah Luna, Vikram Krishnasamy, Louise Saw, Lori Smith, Jennifer Wagner, Jenna Weigand, Mackenzie Tewell, Marilee Kellis, Roumen Penev, Laine McCullough, Jeffrey Eason, Keegan McCaffrey, Cindy Burnett, Kelly Oakeson, Melissa Dimond, Allyn Nakashima, Deidre Barlow, Anna Scherzer, Melanie Sarino, Morgan Schroeder, Rashida Hassan, Colin Basler, Matthew Wise, Laura Gieraltowski
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

On June 26, 2017, a hospital in southern Utah notified the Utah Department of Health of Shiga toxin-producing Escherichia coli (STEC) O157:H7 infections in two children from a small community on the Arizona-Utah border. Both children developed hemolytic uremic syndrome, characterized by hemolytic anemia, acute kidney failure, and thrombocytopenia and died within a few days of illness onset. Over the next few days, several more STEC-associated illnesses were reported in residents of the community. A joint investigation by local and state health agencies from Arizona and Utah and CDC was initiated to identify the outbreak source and prevent additional cases; a total of 12 cases were identified, including the two children who died. Investigators initially explored multiple potential sources of illness; epidemiologic and environmental information revealed cow manure contact as the likely initial cause of the outbreak, which was followed by subsequent person-to-person transmission. One of the outbreak strains was isolated from bull and horse manure collected from a yard near a community household with two ill children. Local health agencies made recommendations to the public related to both animal contact and hand hygiene to reduce the risk for STEC transmission. Animal or animal manure contact should be considered a potential source of STEC O157:H7 during outbreaks in communities where ruminants are kept near the home.
Post-PEGylated and crosslinked polymeric ssRNA nanocomplexes as adjuvants targeting lymph nodes with increased cytolytic T cell inducing properties
Authors: Bo Lou, Ans De Beuckelaer, George R. Dakwar, Katrien Remaut, Johan Grooten, Kevin Braeckmans, Bruno G. De Geest, Enrico Mastrobattista, Stefaan De Koker, Wim E. Hennink
Journal: Journal of Controlled Release (2018)
Tet2 Regulates Osteoclast Differentiation by Interacting with Runx1 and Maintaining Genomic 5-Hydroxymethylcytosine (5hmC)
Authors: Yajing Chu, Zhigang Zhao, David Wayne Sant, Ganqian Zhu, Sarah M. Greenblatt, Lin Liu, Jinhuan Wang, Zeng Cao, Jeanette Cheng Tho, Shi Chen, Xiaochen Liu, Peng Zhang, Jaroslaw P. Maciejewski, Stephen Nimer, Gaofeng Wang, Weiping Yuan, Feng-Chun Yang, Mingjiang Xu
Journal: Genomics Proteomics & Bioinformatics (2018)

Abstract As a dioxygenase, Ten-Eleven Translocation 2 (TET2) catalyzes subsequent steps of 5-methylcytosine (5mC) oxidation. TET2 plays a critical role in the self-renewal, proliferation, and differentiation of hematopoietic stem cells, but its impact on mature hematopoietic cells is not well-characterized. Here we show that Tet2 plays an essential role in osteoclastogenesis. Deletion of Tet2 impairs the differentiation of osteoclast precursor cells (macrophages) and their maturation into bone-resorbing osteoclasts in vitro. Furthermore, Tet2−/− mice exhibit mild osteopetrosis, accompanied by decreased number of osteoclasts in vivo. Tet2 loss in macrophages results in the altered expression of a set of genes implicated in osteoclast differentiation, such as Cebpa, Mafb, and Nfkbiz. Tet2 deletion also leads to a genome-wide alteration in the level of 5-hydroxymethylcytosine (5hmC) and altered expression of a specific subset of macrophage genes associated with osteoclast differentiation. Furthermore, Tet2 interacts with Runx1 and negatively modulates its transcriptional activity. Our studies demonstrate a novel molecular mechanism controlling osteoclast differentiation and function by Tet2, that is, through interactions with Runx1 and the maintenance of genomic 5hmC. Targeting Tet2 and its pathway could be a potential therapeutic strategy for the prevention and treatment of abnormal bone mass caused by the deregulation of osteoclast activities.
An Unusual Occurrence of Dual Tachycardia
Authors: Andrew M. Rosenblum, Adam L. Rosenblum
Journal: JAMA Internal Medicine (2018)

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FRI0342 Does understanding sle matter to disease activity in sle patients?
Authors: A.S. Meara, P. Hackenberger, J. Yedimenko, C. Rodman, S.P. Ardoin, E. peters
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic lupus erythematous (SLE) is a heterogeneous disease with high morbidity and mortality with complex long-term treatments. These dynamic treatments can be daunting especially to the 25%–60% of SLE patients who have cognitive and neuropsychiatric deficits. Patients lacking understanding of their own baseline health status and treatment options cannot effectively collaborate in making informed choices with their physicians. <h3>Objectives</h3> This project aimed to identify SLE patients’ comprehension of their medication regimens and disease outcomes in relation to standard markers of disease activity (SLEDAI) and damage (SLICC DI). <h3>Methods</h3> Patients&gt;18 years were recruited from The Ohio State University (OSU) Lupus Vasculitis Glomerulonephritis (LVG) clinic. An IRB-approved 25-item true/false disease questionnaire was administered to 75 SLE patients who provided informed consent. Individual question and composite scores for each patient were correlated with their SLEDAI and SLICC DI scores. To our knowledge, a disease comprehension questionnaire has never been used in lupus patients. <h3>Results</h3> 75 SLE patients completed the comprehension questionnaire. Lower comprehension was associated with greater disease activity (r=−0.14), while no correlation was found between composite score and disease damage (SLICC DI) (r=−0.03). Figures 1 plot the comprehension composite scores against the SLEDAI. P values were not significant, but trending to correlate with the r. Evaluation of individual questionnaire items demonstrated: approximately 80% of patients did not associate heart disease with lupus, over 25% of patients did not recognise the side effects of prednisone, and over 15% of patients did not know lupus affects bone health. <h3>Conclusions</h3> These preliminary results suggest that patients with more understanding of their SLE diagnosis, comorbidities, and treatments had less measured disease activity. The comprehension questionnaire and SLEDAI characterise patients in their present disease state, so this correlation likely reflects the evolution of patient understanding and the fluctuating nature of their disease. Alternatively, higher disease activity scores represent more severe disease, which could be associated with greater neurocognitive deficits leading to poorer scores on the comprehension questionnaire. The lack of correlation between composite score and SLICC DI is likely attributed to the discrepancy between a metric evaluating current knowledge and a long-term indicator that may derive from decisions made when patients’ comprehension was different than current. These initial results are promising and may represent a cost-effective opportunity for physicians to evaluate and address their patients’ comprehension gaps in an effort to improve shared decision making. However, more data are needed to test the robustness of these trends. <h3>Disclosure of Interest</h3> None declared