tbuckley/cabot-search huggingface dataset:
Abstract P116: The Oral Glucose Tolerance Test is Highly Reproducible for the Diagnosis of Diabetes in Africans: The Africans in America Study
Authors: Sara M Briker, Regine Mugeni, Margrethe F Horlyck-Romanovsky, Jessica Y Aduwo, Christopher W DuBose, Stephanie T Chung, Joon Ha, Arthur Sherman, Anne E Sumner, Lilian S Mabundo
Journal: Circulation (2019)

Introduction: As the diabetes epidemic spreads across Africa, the oral glucose tolerance test (OGTT) has the potential to provide important information on glucose tolerance category for the individual and across the population. However, for both patient care and the collection of prevalence statistics, there needs to be a high degree of certainty that the diagnosis made by a single OGTT is reproducible. There are no rigorous studies on the reproducibility of the OGTT in Africans. Objective: By performing two OGTT in African-born blacks living in the Washington DC area, our goal was to evaluate the reproducibility of: a) the glucose tolerance category b) time to glucose peak, c) shape of glucose curve, d) glucose concentration at 60 minutes. Methods: The participants were 90 African-born blacks (66% male (59/90), age 40±11y (mean±SD), BMI 27.6±4.6 kg/m 2 ), who self-identified as healthy and were enrolled in the Africans in America cohort. Two OGTT were performed 10±8 days apart. At each OGTT plasma samples were taken at -15, 0, 30, 60, 90 and 120 minutes. Diabetes (DM), prediabetes (pre-DM) and normal glucose tolerance (NGT)was defined by ADA guidelines for glucose. The shape of the glucose curve was characterized as monophasic, biphasic or indeterminate. During the OGTT, glucose at 60 minutes ≥ 155 mg/dL was defined as elevated. The κ-statistic was used to evaluate reproducibility (slight 0.00 to 0.20, fair 0.21 to 0.40; substantial 0.61 to 0.80, excellent 0.81 to 1.0). Results: At OGTT-1, DM, pre-DM and NGT occurred in 26% (23/90), 27% (24/90) and 48% (43/90), resp. At OGTT-2, DM, pre-DM and NGT occurred in 21% (19/90), 28% (25/90) and 51% (46/90) resp. Reproducibility for the diagnosis of glucose tolerance status (NGT, pre-DM, or DM) was just substantial (κ=0.66). However, reproducibility for the diagnosis of diabetes (DM or no DM) was excellent (κ=0.88). Furthermore, no one without DM at OGTT-1 was identified as having DM at OGTT-2. The reproducibility of time to glucose peak was only fair (κ=0.32), but 100% of participants with DM had peak glucose after 30 min. Similarly, the shape of the glucose curve had fair reproducibility (κ=0.21), but no one with DM had a biphasic curve. For elevated 60 min glucose, reproducibility was substantial (κ=0.62) and 96% (22/23) of the participants with DM had elevated glucose at 60 min. Conclusion: When duplicate OGTT were performed in Africans, the diagnosis of DM and the morphology of the glucose curves were highly reproducible.
SON haploinsufficiency causes impaired pre-mRNA splicing of CAKUT genes and heterogeneous renal phenotypes
Authors: Jung-Hyun Kim, Eun Young Park, David Chitayat, David L. Stachura, Jörg Schaper, Kristin Lindstrom, Tamison Jewett, Dagmar Wieczorek, Jos M. Draaisma, Margje Sinnema, Christianne Hoeberigs, Maja Hempel, Kristine K. Bachman, Andrea H. Seeley, Joshua K. Stone, Hyun Kyung Kong, Lana Vukadin, Alexander Richard, Deepali N. Shinde, Kirsty McWalter, Yue Cindy Si, Ganka Douglas, Ssang-Taek Lim, Lisenka E.L.M. Vissers, Mathieu Lemaire, Eun-Young Erin Ahn
Journal: Kidney International (2019)
Abstract P030: Association of Ideal Cardiovascular Health and Plasminogen Activator Inhibitor-1 From Early Adulthood to Middle Age: the Coronary Artery Risk Development in Young Adults Study
Authors: Lauren Y Lee, Douglas E Vaughan, Laura Colangelo, Donald M Lloyd-Jones, Sadiya S Khan
Journal: Circulation (2019)

Background: Ideal cardiovascular health (CVH) is associated with a lower incidence of cardiovascular disease (CVD). Therefore identification of biomarkers that may mediate risk between CVH and CVD may offer novel approaches in CVD prevention. One potential biomarker is plasminogen activator inhibitor-1 (PAI-1), which has been associated with increased risk of CVD. The aim of this study is to assess the relationship between CVH scores and PAI-1 levels from young adulthood to mid-life. Methods: Plasma PAI-1 levels were measured in a subset of randomly selected participants (n=1200) from the Coronary Artery Risk Development in Young Adults (CARDIA) study at year 7 (Y7) and Y20. Among them, 911 participants at Y7 and 830 participants at Y20 had available data on CVH status. We calculated CVH scores (range 0-14) and categorized as low (0-7), moderate (8-11), and high (12-14). We performed multivariable linear regression to study the association of CVH and PAI-1 at Y7 and Y20 after adjustment for age, sex, race, education, and center. Results: At Y7, participants (mean age 32.3±3.5 years) had a mean CVH score of 11.1 (±1.8) and mean PAI-1 level of 20.0 ng/mL (±21.2) with an adjusted correlation coefficient of -0.29 (p&lt;0.0001) (TABLE) . By Y20, mean CVH score of the participants had declined to 10.1 (±2.3) and mean PAI-1 level had increased to 36.2 ng/mL (±37.1) with an adjusted correlation coefficient of -0.46 (p&lt;0.0001). Among participants with high, moderate, and low CVH, PAI-1 levels were higher at Y20 compared to Y7 (high: 14.7 to 18.0 ng/mL, moderate: 23.9 to 36.9 ng/mL, low: 27.3 to 64.6 ng/mL). At both Y7 and Y20, mean level of PAI-1 was significantly higher in participants with moderate or low CVH (compared with high CVH). Conclusion: Higher CVH score is associated with lower plasma levels of PAI-1 from young adulthood to mid-life. PAI-1 levels increased among all CVH categories with aging; however, participants with high CVH had the smallest increase in PAI-1 and PAI-1 levels remained lower than even young adults with moderate or low CVH.
Carcinomas of the renal pelvis, ureters, and urinary bladder arise by similar carcinogenic pathways: A pathoepidemiological analysis.
Authors: Amanda Nizam, Donald Henson, Jeanny B. Aragon-Ching
Journal: Journal of Clinical Oncology (2019)

403 Background: Urothelial carcinomas comprise the most common malignant tumors in the urinary tract. Kidney epithelial cancers, on the other hand, have a different pathoepidemiologic incidence and characteristics. We report a population-based analysis of the histopathology of upper and lower urinary tract cancers as an approach to exploring the relationship of tumors that share similar morphologic phenotypes. Our results depend on observations made 65 years ago that age of diagnosis and age specific incidence rates generated straight lines when plotted as logarithms. Methods: Data from 2000 through 2014 from the SEER Program were used to calculate incidence rates of renal, renal pelvis, ureter and urinary bladder cancers. Graphic plots of the epidemiologic patterns were analyzed relating to incidence and age-specific rates of these upper and lower tract carcinomas. The graphic analysis included evaluation of age frequency density plots and double logarithmic plots (log-log) of age-specific incidence rates and age at diagnosis. Results: Cancers of the kidney are initially more frequent than cancers of the urinary bladder, but after age 60, cancers of the bladder become more common with age-specific rates rapidly rising in all age groups. The age frequency density plot for renal cancers peaks earlier, around age 60, indicating a potentially different tumorigenic process. While the log-log plots reveal near parallel proportional rate patterns for cancers of the renal pelvis, ureters, and urinary bladder, while the rate for the cancer of the kidney was not parallel on inspection. Similar slopes indicate that cancer incidence is increasing at near similar rates regardless of the incidence of each cancer. Thus, the percentage change per unit time for cancers of the renal pelvis, ureters, and bladder is comparable. Conclusions: Tumors that arise from the renal pelvis, ureters, and urinary bladder are pathogenically related and share a common carcinogenic field based on pathoepidemiologic analyses.
Abstract P100: Geographic Disparities in Hypertensive Disorders of Pregnancy: An Environment-Wide Association Study
Authors: Hui Hu, Thomas A Pearson, Jinying Zhao, Mattia Prosperi, Sonja A Rasmussen, Xiao Hong, Linda B Cottler
Journal: Circulation (2019)

Hypertensive disorders of pregnancy (HDP) are significant contributor to maternal and infant morbidity and mortality, and large geographic disparities exist. Although the importance of an individual’s surrounding environment as a potentially modifiable risk factor for HDP has been recognized and multiple environmental factors have been associated with HDP, only a few components in the environment have been assessed, often separately, with no consideration of the totality of environment. To address this, we conducted an environment-wide association study (EWAS) using the Florida Vital Statistics Birth Records including 2,119,324 women with conception dates between January 1, 2005 and December 31, 2014. EWAS is an agnostic and hypothesis-free approach. A wide range of environmental data from 12 sources were collected, harmonized, integrated, and spatiotemporally linked to the women based on their geocoded residential address and pregnancy period. A total of 5,510 factors characterizing women’s surrounding natural, built, and social environment during pregnancy (i.e. climate, air pollution, noise, greenness, walkability, food access, socioeconomics, social capital, housing, and safety) were included in the analysis. A random 50:50 split divided the data into training and testing sets. Environmental factors were individually examined after adjusting for age, race/ethnicity, education, marital status, WIC (Women, Infants, and Children Nutrition Program) recipient, smoking during pregnancy, pre-pregnancy BMI, parity, season, and year of conception. Mixed-effects models were used to account for the multilevel structure. A factor is deemed as “significant” if it has a false discovery rate-adjusted p-value (or q-value)&lt;0.01 in the training set and a p-value&lt;0.01 in the testing set. We identified 1,208 factors significantly associated with HDP, with strong associations observed between HDP and three categories of environmental factors: 1) neighborhood social capital (i.e. ZIP Code-level density of fitness and recreational sports centers, OR per standard deviation increase [OR sd ]: 0.34, 99% CI: 0.25, 0.46), 2) food access (i.e. low access tract at 10 miles, OR=1.27, 99% CI: 1.17, 1.47), and 3) bikeability (OR sd =0.86, 99% CI: 0.83, 0.89). EWAS is a promising approach to identify novel environmental factors associated with cardiovascular diseases. Environmental exposures appear to play a critical role, both in identifications of pregnant women at increased risk of HDP and in determinations of potential target for public health interventions.
Diverse tumour susceptibility in Collaborative Cross mice: identification of a new mouse model for human gastric tumourigenesis
Authors: Pin Wang, Yunshan Wang, Sasha A Langley, Yan-Xia Zhou, Kuang-Yu Jen, Qi Sun, Colin Brislawn, Carolina M Rojas, Kimberly L Wahl, Ting Wang, Xiangshan Fan, Janet K Jansson, Susan E Celniker, Xiaoping Zou, David W Threadgill, Antoine M Snijders, Jian-Hua Mao
Journal: Gut (2019)

The Collaborative Cross (CC) is a mouse population model with diverse and reproducible genetic backgrounds used to identify novel disease models and genes that contribute to human disease. Since spontaneous tumour susceptibility in CC mice remains unexplored, we assessed tumour incidence and spectrum.We monitored 293 mice from 18 CC strains for tumour development. Genetic association analysis and RNA sequencing were used to identify susceptibility loci and candidate genes. We analysed genomes of patients with gastric cancer to evaluate the relevance of genes identified in the CC mouse model and measured the expression levels of ISG15 by immunohistochemical staining using a gastric adenocarcinoma tissue microarray. Association of gene expression with overall survival (OS) was assessed by Kaplan-Meier analysis.CC mice displayed a wide range in the incidence and types of spontaneous tumours. More than 40% of CC036 mice developed gastric tumours within 1 year. Genetic association analysis identified Nfκb1 as a candidate susceptibility gene, while RNA sequencing analysis of non-tumour gastric tissues from CC036 mice showed significantly higher expression of inflammatory response genes. In human gastric cancers, the majority of human orthologues of the 166 mouse genes were preferentially altered by amplification or deletion and were significantly associated with OS. Higher expression of the CC036 inflammatory response gene signature is associated with poor OS. Finally, ISG15 protein is elevated in gastric adenocarcinomas and correlated with shortened patient OS.CC strains exhibit tremendous variation in tumour susceptibility, and we present CC036 as a spontaneous laboratory mouse model for studying human gastric tumourigenesis.
Abstract P369: Coronary Heart Disease and Mortality Following a Breast Cancer Diagnosis
Authors: Aixia Guo, Kathleen Zhang, Randi Foraker
Journal: Circulation (2019)

Background: Coronary heart disease (CHD) is a leading cause of death for breast cancer survivors. While cardiotoxic breast cancer treatments are linked with cardiovascular injury and an increased risk of CHD, current risk prediction models for CHD do not consider the effect of cancer treatments and likely underestimate CHD and mortality risk in this population. Methods: We conducted support vector machine, decision tree, and logistic regression models on electronic health record data to evaluate the independent and joint effects of cardiovascular health (CVH) and cancer treatments on post-treatment CHD and all-cause mortality occurring within 10 years among 1934 women diagnosed with breast cancer in 2006 and 2007 at our medical center. CVH was classified as poor, intermediate, or ideal according to 5 factors: smoking, body mass index, blood pressure, glucose/hemoglobin A1c, and cholesterol. We considered anthracyclines and hormone therapies as cardiotoxic cancer treatments in these analyses. Results: Women with ideal CVH scores had a lower risk of CHD (23.7%) and death (14.3%) compared to those with poor CVH scores (61.9% for CHD, 32.5% for death). Women exposed to cancer treatments had a higher risk of CHD (58.9%) and death (37.5%) compared to women who were not exposed (29.1% for CHD, 15.4% for death). Meanwhile, the joint effects of poor CVH and receipt of cardiotoxic cancer treatments conferred a much higher risk of CHD (75.9%) and death (39.5%) compared to women with ideal CVH who did not receive treatments (20.8% for CHD, 11.2% for death). All approaches ( Figure 1 ) demonstrated the highest area under the curve (AUC) for models considering the joint effects of CVH and cancer treatments (range: 0.70-0.75), followed by the independent effects of CVH (range: 0.65-0.66) and the independent effects of cancer treatments (range: 0.59-0.63). Conclusions: Cancer treatment data should be considered along with traditional cardiovascular risk factor data in the prediction of CHD and mortality among breast cancer survivors.
Abstract P366: Pooled Cohort Equation Performance in Primary and Secondary Prevention Subgroups of the SystolicBlood Pressure Intervention Trial (SPRINT)
Authors: Timothy B Plante, Stephen P Juraschek, Neil A Zakai, Russell P Tracy, Mary Cushman
Journal: Circulation (2019)

Background: The Pooled Cohort Equation (PCE) estimates 10-y atherosclerotic cardiovascular disease (ASCVD) risk among adults aged 40-79 years without CVD. Recent studies applied the PCE to mixed primary (1°) and secondary (2°) prevention populations to predict risk of future CVD events. However, the PCE is not validated in 2° prevention populations. We studied the impact of prior CVD on PCE performance in a 2° prevention population of the SPRINT trial. Methods: SPRINT randomized 9,361 adults with hypertension and ≥1 CVD risk factor or prior ASCVD to standard or intensive BP control. Excluding those age &gt;79 years (n=1,158) or missing PCE covariates (n=52), we calculated 10-year ASCVD risk at baseline using the PCE. We assessed PCE discrimination with the C-statistic among all SPRINT participants and among 1° and 2° prevention subgroups. We estimated the hazard ratio (HR) for incident ASCVD events comparing the 2° to the 1° prevention group, controlling for baseline PCE-predicted 10-y risk. Results: Of the 8,151 included participants, 6,874 (84%) and 1,277 (16%) were in the 1° and 2° prevention groups, respectively. Mean (SD) age was 66 (8) years, 35% were female, 34% were black. Median (IQR) baseline predicted 10-year ASCVD risk in the 1° prevention group was lower than the 2° prevention group (P&lt;0.001; Table ). In the 3.3 years of follow-up, ASCVD events occurred more frequently in the 2° prevention group than the 1° prevention group (P&lt;0.001). The C-statistic was 0.618 (95% CI 0.589, 0.646) in the entire analytic population, and was non-significantly higher among the 1° prevention subgroup. Comparing the 2° to 1° prevention population, HR for incident ASCVD events was 2.6 (95% CI 2.1, 3.3) when controlling for baseline PCE-estimated 10-y risk. Conclusions: Adults with prior ASCVD events have a nearly 3-fold higher risk of subsequent events. This study demonstrates that the PCE underestimates risk of recurrent events in 2° prevention populations and use in mixed populations should be avoided.
Abstract P246: Fish Oil Supplementation During Early Life Improves Metabolic Health in Diet Induced Obesity
Authors: Latha Ramalingam, Kalhara Menikdewella, Shane Scoggin, Naima Moustaid-Moussa
Journal: Circulation (2019)

Objective: Obesity is global epidemic and a complex disease that increases the risk for cardiovascular and metabolic disorders. Over half of American women of child bearing age are either obese or overweight, putting their offspring at high risk for childhood obesity and comorbidity. Hence, maternal programming through diet is critical for prevention of obesity and its metabolic complications in the offspring. Fish oil (FO), rich in very long chain omega 3 polyunsaturated fatty acids exert various health benefits such as reduced serum triglycerides, inflammation and insulin resistance. However, it remains unclear whether maternal and/or post-natal consumption of FO protects offspring from adverse effects of consuming high fat (HF) diet. Methods: Female mice were fed low fat diets (LF, control diet), HF diets supplemented without (HF) or with FO for 8 weeks pre-pregnancy through lactation, and bred to low fat fed male mice. After weaning, male and female offspring from HF or FO dams were either continued on their respective diets (HF-HF and FO-FO) or switched to the other diet (HF-&gt;FO and FO-&gt;HF) and compared to LF. Serum, adipose tissue, and other tissues were collected at the end of the feeding period for further analyses. Results: HF fed mice of both sexes had significantly higher body weight and were insulin resistant compared to LF mice. Male offspring who continued on FO during pregnancy and early life (FO-FO) demonstrated significantly higher glucose clearance and insulin sensitivity compared to offspring that were switched to HF (FO-HF) (P&lt;0.05). However, no differences were observed between pups born to HF fed dams. Interestingly, in the female offspring, all groups that received FO either during pregnancy or early life (FO-FO, FO-HF, HF-FO) demonstrated better glucose tolerance than HF-HF groups. Furthermore, adiposity and inflammation was significantly lower in all pups that received fish oil either during pregnancy or early life (FO-FO, FO-HF, HF-FO) compared to HF fed mice in both male and female pups. Conclusions: Supplementation of FO during pregnancy and early life is more beneficial than treating with FO either during pregnancy or in neonatally.
Making a case for constructive reductionism
Authors: Christian P. Müller
Journal: Behavioral and Brain Sciences (2019)

Abstract Borsboom and colleagues argue that reductionism in psychopathology research has not provided the expected insights. Instead, they suggest a systems approach of interacting syndromes, which, however, falls short of a perspective for empirical testing. Here, a combination of both approaches is suggested: a reductionistic empirical approach allowing testability, synergistic with a constructivistic systems appraisal of syndrome networks – a constructive reductionism .
SAT0732-HPR Resilience and positive affect are related to the experience of fatigue in patients with a rheumatic disease
Authors: E Taal, K Schreurs, L Guddorf, C Bode, M van de Laar
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Fatigue is a common symptom in patients with a rheumatic disease. Resilience, the ability to bounce back or recover from stress, has been found to be related to lower fatigue in patients with cancer, traumatic brain injury, cardiac disease and fibromyalgia (see e.g. [1]) <h3>Objectives</h3> To study the relationships of resilience and the resilience related factors positive affect, acceptance and engaged living with fatigue in patients with rheumatic diseases. <h3>Methods</h3> 57 patients with a rheumatic disease (rheumatoid arthritis, 70%; osteoarthritis, 11%; others, 9%) completed an online questionnaire. Fatigue was assessed with SF-36 vitality scale; pain with a VAS; Resilience with BRS and resilience related factors with PANAS (positive affect), AAQ-II (Acceptance) and ELS (engaged living). Data were analysed with hierarchical multiple regression analyses. <h3>Results</h3> Resilience, positive affect, acceptance and engaged living were multivariate significantly related to fatigue (R<sup>2</sup> =0.54; P≤0.001). Resilience (β=0.29; P≤0.05) and positive affect (β=0.39; P≤0.01) were significant individual predictors of lower fatigue in multiple regression analysis. Acceptance and engaged living were not significantly related with fatigue in the multivariate model. The relationship between resilience and fatigue was partially mediated by positive affect. When pain was included in the model the relations of resilience (β=0.27; P≤0.05) and positive affect (β=0.34; P≤0.05) with fatigue remained significant. <h3>Conclusions</h3> Resilience and positive affect may be predictors of decreased fatigue in rheumatic patients. Further longitudinal studies are needed to examine the causality of these relationships. <h3>References</h3> Smith BW, Dalen J, Wiggins K, Tooley E, Christopher P, Bernard J. The brief resilience scale: Assessing the ability to bounce back. Int J Behav Med 2008;15(3):194–200. <h3>Disclosure of Interest</h3> None declared
Nrf2 activation via <i>Keap1</i> deletion or sulforaphane treatment reduces Ova‐induced sinonasal inflammation
Authors: Nyall R. London, Anuj Tharakan, Michelle Mendiola, Mengfei Chen, Alex Dobzanski, Thomas E. Sussan, Michael Zaykaner, Andrew H. Han, Andrew P. Lane, Venkataramana Sidhaye, Shyam Biswal, Murugappan Ramanathan
Journal: Allergy (2019)

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