tbuckley/cabot-search huggingface dataset:
Abstract MP15: Television Watching in Mid-Life and Long-Term Diabetes Risk: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Michael Fang, Natalie R Daya, Morgan Grams, Elizabeth Selvin
Journal: Circulation (2020)

Background: Prolonged television watching is associated with numerous health problems. However, its long-term impact and its joint effect with other risk factors on the development of diabetes remains unclear. Methods: We conducted a prospective cohort analysis of television watching and incident diabetes using data from the Atherosclerosis Risk in Communities (ARIC) Study. We used Cox regression models and considered television watching independently and jointly with physical activity, weight status, and family history of diabetes. At baseline (1987-1989), participants self-reported frequency of television watching, leisure-time physical activity, and parental history of diabetes. Body mass index was calculated from measured weight and height and converted into weight status categories. Incident diabetes was defined as having a fasting glucose &gt;126 mg/dL or non-fasting glucose &gt;200 mg/dL, or self-report of a diagnosis of diabetes or diabetes medication with follow-up to 2017. Results: There were 13,127 participants without diabetes at baseline (mean age, 54, 23% black, 56% female). During 21 years of follow-up, there were 4,280 incident cases of diabetes. Compared to those who watched low levels of television, those who watched medium and high levels were more likely to develop diabetes (HRs 1.13 and 1.51, Figure ). Other risk factors combined with television watching jointly increased the risk of incident diabetes. That is, even within categories of physical activity, weight status, and family history, television watching was an independent risk factor for diabetes. Conclusion: Currently, there is substantial debate regarding the health effects of screen-time. Our study suggests prolonged television watching confers substantial long-term risk for diabetes, even in the setting of other major risk factors. Decreasing exposure to television and other screens may be an important target for diabetes prevention.
Diabetes, Cognitive Decline, and Mild Cognitive Impairment Among Diverse Hispanics/Latinos: Study of Latinos–Investigation of Neurocognitive Aging Results (HCHS/SOL)
Authors: Hector M. González, Wassim Tarraf, Kevin A. González, Myriam Fornage, Donglin Zeng, Linda C. Gallo, Gregory A. Talavera, Martha L. Daviglus, Richard B. Lipton, Robert Kaplan, Alberto R. Ramos, Melissa Lamar, Jianwen Cai, Charles DeCarli, Neil Schneiderman
Journal: Diabetes Care (2020)

OBJECTIVE Hispanics/Latinos are the largest ethnic/racial group in the U.S., have the highest prevalence of diabetes, and are at increased risk for neurodegenerative disorders. Currently, little is known about the relationship between diabetes and cognitive decline and disorders among diverse Hispanics/Latinos. The purpose of this study is to clarify these relationships in diverse middle-aged and older Hispanics/Latinos. RESEARCH DESIGN AND METHODS The Study of Latinos–Investigation of Neurocognitive Aging (SOL-INCA) is an ancillary study of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). HCHS/SOL is a multisite (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA), probability-sampled (i.e., representative of targeted populations), and prospective cohort study. Between 2016 and 2018, SOL-INCA enrolled diverse Hispanics/Latinos aged ≥50 years (n = 6,377). Global cognitive decline and mild cognitive impairment (MCI) were the primary outcomes. RESULTS Prevalent diabetes at visit 1, but not incident diabetes at visit 2, was associated with significantly steeper global cognitive decline (βGC = −0.16 [95% CI −0.25; −0.07]; P &amp;lt; 0.001), domain-specific cognitive decline, and higher odds of MCI (odds ratio 1.74 [95% CI 1.34; 2.26]; P &amp;lt; 0.001) compared with no diabetes in age- and sex-adjusted models. CONCLUSIONS Diabetes was associated with cognitive decline and increased MCI prevalence among diverse Hispanics/Latinos, primarily among those with prevalent diabetes at visit 1. Our findings suggest that significant cognitive decline and MCI may be considered additional disease complications of diabetes among diverse middle-aged and older Hispanics/Latinos.
Rapid Corneal Nerve Fiber Loss: A Marker of Diabetic Neuropathy Onset and Progression
Authors: Evan J.H. Lewis, Leif E. Lovblom, Maryam Ferdousi, Elise M. Halpern, Maria Jeziorska, Daniele Pacaud, Nicola Pritchard, Cirous Dehghani, Katie Edwards, Sangeetha Srinivasan, Roni Mintz Shtein, Nathan Efron, Mitra Tavakoli, Vera Bril, Rayaz Ahmed Malik, Bruce A. Perkins
Journal: Diabetes Care (2020)

OBJECTIVE Corneal nerve fiber length (CNFL) represents a biomarker for diabetic distal symmetric polyneuropathy (DSP). We aimed to determine the reference distribution of annual CNFL change, the prevalence of abnormal change in diabetes, and its associated clinical variables. RESEARCH DESIGN AND METHODS We examined 590 participants with diabetes (399 with type 1 diabetes [T1D] and 191 with type 2 diabetes [T2D]) and 204 control patients without diabetes with at least 1 year of follow-up and classified them according to rapid corneal nerve fiber loss (RCNFL) if CNFL change was below the 5th percentile of the control patients without diabetes. RESULTS Control patients without diabetes were 37.9 ± 19.8 years old, had median follow-up of three visits over 3.0 years, and mean annual change in CNFL was −0.1% (90% CI −5.9% to 5.0%). RCNFL was defined by values exceeding the 5th percentile of 6% loss. Participants with T1D were 39.9 ± 18.7 years old, had median follow-up of three visits over 4.4 years, and mean annual change in CNFL was −0.8% (90% CI −14.0% to 9.9%). Participants with T2D were 60.4 ± 8.2 years old, had median follow-up of three visits over 5.3 years, and mean annual change in CNFL was −0.2% (90% CI −14.1% to 14.3%). RCNFL prevalence was 17% overall and was similar by diabetes type (64 T1D [16.0%], 37 T2D [19.4%], P = 0.31). RNCFL was more common in those with baseline DSP (47% vs. 30% in those without baseline DSP, P = 0.001), which was associated with lower peroneal conduction velocity but not with baseline HbA1c or its change over follow-up. CONCLUSIONS An abnormally rapid loss of CNFL of 6% per year or more occurs in 17% of diabetes patients. RCNFL may identify patients at highest risk for the development and progression of DSP.
EHD1 Modulates Cx43 Gap Junction Remodeling Associated With Cardiac Diseases
Authors: Tania Martins-Marques, Steve Catarino, Alexandre Gonçalves, Daniela Miranda-Silva, Lino Gonçalves, Pedro Antunes, Gonçalo Coutinho, Adelino Leite Moreira, Inês Falcão Pires, Henrique Girão
Journal: Circulation Research (2020)

Rationale: Efficient communication between heart cells is vital to ensure the anisotropic propagation of electrical impulses, a function mainly accomplished by gap junctions (GJ) composed of Cx43 (connexin 43). Although the molecular mechanisms remain unclear, altered distribution and function of gap junctions have been associated with acute myocardial infarction and heart failure. Objective: A recent proteomic study from our laboratory identified EHD1 (Eps15 [endocytic adaptor epidermal growth factor receptor substrate 15] homology domain-containing protein 1) as a novel interactor of Cx43 in the heart. Methods and Results: In the present work, we demonstrate that knockdown of EHD1 impaired the internalization of Cx43, preserving gap junction-intercellular coupling in cardiomyocytes. Interaction of Cx43 with EHD1 was mediated by Eps15 and promoted by phosphorylation and ubiquitination of Cx43. Overexpression of wild-type EHD1 accelerated internalization of Cx43 and exacerbated ischemia-induced lateralization of Cx43 in isolated adult cardiomyocytes. In addition, we show that EHDs associate with Cx43 in human and murine failing hearts. Conclusions: Overall, we identified EHDs as novel regulators of endocytic trafficking of Cx43, participating in the pathological remodeling of gap junctions, paving the way to innovative therapeutic strategies aiming at preserving intercellular communication in the heart.
Abstract P1-05-04: miR551b-3p promotes Oncostatin M signaling in breast cancer
Authors: Anjali Geethadevi, Deepak Parashar, Miriam Ragle Aure, Jasmine George, Changliang Chen, Jyotsna Mishra, Andliena Tahiri, Bindu Nair, Amadou Camara, Vessela N Kristensen, Sunila Pradeep, Pradeep Chaluvally Raghavan
Journal: Cancer Research (2020)

Abstract An increased expression of oncogenic microRNA miR551b-3p (also known as miR551b) occurs in a subset of breast cancer due to genomic amplification of 3q26.2 locus. Using in silico and clinical sample analysis of breast cancer patient datasets, we identified that those breast cancer samples that encompass miR551b amplification express high levels of STAT3 mRNA and Oncostatin (OSM) family genes in triple-negative breast cancer (TNBC). Furthermore, high expression of Oncostatin family genes associates with poor outcome in estrogen receptor- negative breast cancer patients. In this study, we identified a previously unexplored mechanism that miR551b-3p promotes breast cancer progression and tumor growth by direct interaction of miR551b-3p with STAT3 promoter thereby activating STAT3 transcription. As a consequence, STAT3 upregulates a cytokine Oncostatin and its receptor Oncostatin M receptor (OSMR) and their interaction further induces STAT3 phosphorylation and an autocrine self-reinforcing loop in TNBC cells. In this study, we demonstrate that overexpression of miR551b-3p promoted proliferation, invasion and migration, epithelial to mesenchymal transition (EMT) and spheroid formation of breast cancer cells and its inhibition decreased the expression of miR551b-3p by inhibiting OSM, OSMR, IL6ST, IL31RA, phosphorylated and total STAT3 in breast cancer cells and reduced tumor cell growth. Overall, our results provide the first evidence that miR551b regulates OSM family gene expression by activating STAT3 and thereby promoting tumor cell growth and metastasis in breast cancer cells. Therefore, targeting miR-551b-3p-STAT3-OSMR axis and inhibiting their levels will provide an unprecedented therapeutic opportunity in breast cancer. Citation Format: Anjali Geethadevi, Deepak Parashar, Miriam Ragle Aure, Jasmine George, Changliang Chen, Jyotsna Mishra, Andliena Tahiri, Bindu Nair, Amadou Camara, Vessela N Kristensen, Sunila Pradeep, Pradeep Chaluvally Raghavan. miR551b-3p promotes Oncostatin M signaling in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-05-04.
Abstract 44: Childhood Predictors of Type 2 Diabetes in Young Adulthood to Middle-age: The International Childhood Cardiovascular Cohort (i3c) Consortium
Authors: Tian Hu, David R Jacobs, Alan R Sinaiko, Lydia A Bazzano, Trudy L Burns, Stephen R Daniels, Terence Dwyer, Markus Juonala, Ronald J Prineas, Olli T Raitakari, Elaine M Urbina, Alison Venn, Jessica G Woo, Julia Steinberger
Journal: Circulation (2020)

Introduction: Although childhood obesity is related to incident adult type 2 diabetes (T2DM), whether other childhood risk factors relate to T2DM is not clear and no childhood risk score has been established to help with prediction of T2DM. Methods: We examined childhood risk factors in The International Childhood Cardiovascular Cohort (i3C) Consortium with a goal of developing a risk score for predicting adult T2DM. The pooled datasets included childhood measurements during the 1970s to 1990s. Participants were re-contacted at mean age 40 yr and completed a health questionnaire including self-report of adult T2DM (occurrence age, medication use). Results: N = 4,425 i3C participants with measurements during ages 3-19 yr. 225 (5.1%) reported onset of T2DM between ages 20-55 (mean 38.4) years (82% reported use of a valid antidiabetic medication). After stepwise regression, age-sex standardized deviates (mean of all repeated measures during ages 3-19 yr) of body mass index (BMI), glucose and ln(insulin) were associated with incident T2DM; the unadjusted risk curves visibly steepened at about 0.75 standard deviates (Figure, top panel). In multivariable models, BMI, glucose and ln(insulin) in a single model were associated with adult T2DM after adjustment for sex, race, cohort, and individual mean childhood age and calendar year. Prediction of incident T2DM was directly related to the number of the three risk factors with levels above +0.75 standard deviates (0: 3.2% (96/2966), 1: 6.2% (63/1,012), 2: 14.3% (56/392), 3:18.2% (10/55); the corresponding adjusted HR (95%CI) for the counts were 1 (reference), 1.8 (1.3, 2.4), 4.7 (3.3, 6.5), and 6.7 (3.5, 13.1), respectively). The +0.75 standard deviates in natural units are given in the Figure (bottom panel), e.g. about 92 mg/dL for glucose at age 12-14. Conclusion: The study suggests that a childhood risk score composed of BMI, glucose and insulin is a strong predictor of adult T2DM. Provisionally suggested cutpoints are lower than currently defined normal.
Abstract P255: Moderate Alcohol Consumption and the Risk of Acute Ischemic Stroke and All-Cause Mortality: The Million Veteran Program
Authors: Rebecca Song, Hugo J Aparicio, Sudha Seshadri, Kelly Cho, Peter W Wilson, J. M Gaziano, Luc Djousse
Journal: Circulation (2020)

Introduction: Moderate alcohol consumption has been associated with lower risk of acute ischemic stroke (AIS) in the general population, but this relation has not been examined among U.S. Veterans. Furthermore, inconsistent data are available on the relation of alcohol and all-cause mortality. Methods: Million Veteran Program (MVP) participants who completed a lifestyle survey were eligible for analysis (n=335,754). We combined grams of ethanol in wine, beer, and spirits from the food frequency questionnaire to estimate grams/day (g/d). Participants were categorized into categories of: Never, former, or current drinkers of ≤6 g/d, &gt;6-12 g/d, &gt;12-24 g/d, &gt;24-36 g/d, &gt;36-48 g/d, and &gt;48 g/d. We defined incident AIS as 1 inpatient or 2 outpatient codes (ICD-9 433-434.XX, 436.XX, 437.0, 437.6; ICD-10 codes I63.XX, I65-I66.XX, I67.2, I67.6, I67.8) using the VA electronic health record. Participants with prevalent CVD (n=93,496), missing alcohol data (n=24,871), no follow-up time (n=18,948) or missing age or sex (n=135) were excluded. We used a Cox Proportional Hazards model to relate alcohol consumption and AIS and mortality (separately) adjusting for age, sex, race, body mass index, smoking, education, exercise, DASH score, diabetes, and hypertension status. A sensitivity analysis using simulation reclassifying never drinkers with prevalent comorbidities assessed the impact of potential exposure misclassification on effect estimates. Results: Among 198,304 participants, the mean age was 64y (SD=12), and 10% were women. During a mean follow up of 3.3 years, 3,834 AIS and 7,020 deaths occurred. Using never drinkers as the reference group, we identified a 20-26% (95% CI range: 0.42-0.93) lower risk of AIS, and a 29-39% (95% CI range: 0.46-0.80) lower risk of mortality among drinkers of &gt;0-36 g/d, respectively (Figure 1). In sensitivity analyses, HRs were attenuated but the effects remained robust. Conclusion: Our data show a lower risk of AIS and all-cause mortality with moderate alcohol consumption among MVP participants.
Correlation between the expression of hypoxia-inducible factor-1α or histone deacetylase 1/metastasis-associated protein 1 complex and poor prognosis on human pancreatic carcinoma
Authors: K. Miyake, M. Shimada, S. Imura, K. Sugimoto, E. Batmunkh, T. Ikemoto, Y. Morine, T. Yoshizumi
Journal: Journal of Clinical Oncology (2007)

21012 Background: Hypoxia-inducible factor-1a (HIF-1a) is a transcription factor that plays an important role in tumor growth and metastasis by regulating energy metabolism and inducing angiogenesis. Inhibition of histone deacetylase shows a marked inhibition of HIF-1a expression, however, the association between HIF-1a and histone deacetylase 1 (HDAC1) / metastasis-associated protein 1 (MTA1) is not fully understood. Here, we explored the involvement of HIF-1a and HDAC1/MTA1 in human pancreatic carcinoma. Methods: HIF-1a, HDAC1 and MTA1 expressions were detected by immunohistochemistry in surgical specimens obtained from 39 patients with pancreatic carcinoma. The correlations between the expression of HIF-1a, HDAC1 or MTA1 and clinical features, and the prognosis of patients with pancreatic carcinoma were then analyzed. Results: HIF-1a, HDAC1 and MTA1 positive stainings were found in 16 of 39 cases (41%), 22 of 39 cases (56%) and 12 of 39 cases (31%), respectively. There was no correlation between HIF-1a, HDAC1 or MTA1 expression levels and any of the clinical parameters examined. The five-year survival rate for pancreatic carcinoma patients with HIF-1a and HDAC1 positive stainings were significantly lower than for those patients with HIF-1a and HDAC1 negative stainings (P = 0.0243 and 0.0433). The MTA1 positive stainings group did not have a significantly worse prognosis than the MTA1 negative stainings group (P = 0.9694). In addition, the five-year survival rate for the HDAC1/MTA1 positive stainings group was statistically significantly worse than for the other groups (P = 0.0386). Conclusions: These results suggest that HIF-1a expression may be regulated through HDAC1/MTA1, which is associated with a poor prognosis on human pancreatic carcinoma, and indicate that HIF-1a and HDAC1/MTA1 is a promising therapeutic target in pancreatic carcinoma treatment. No significant financial relationships to disclose.
Early-life antibiotic use and risk of asthma and eczema: results of a discordant twin study
Authors: Elise M.A. Slob, Bronwyn K. Brew, Susanne J.H. Vijverberg, Chantal J.A.R. Kats, Cristina Longo, Mariëlle W. Pijnenburg, Toos C.E.M. van Beijsterveldt, Conor V. Dolan, Meike Bartels, Patrick Magnusson, Paul Lichtenstein, Tong Gong, Gerard H. Koppelman, Catarina Almqvist, Dorret I. Boomsma, Anke H. Maitland-van der Zee
Journal: European Respiratory Journal (2020)

Rationale Early-life antibiotic use has been associated with the development of atopic diseases, but the aetiology remains unclear. To elucidate the aetiology, we used a discordant twin design to control for genetic and environmental confounding. Methods We conducted a retrospective cohort study in twins aged 3–10 years from the Netherlands Twin Register (NTR, n=35 365) and a replication study in twins aged 9 years from the Childhood and Adolescent Twin Study in Sweden (CATSS, n=7916). Antibiotic use was recorded at age 0–2 years. Doctor-diagnosed asthma and eczema were reported by parents when children were aged 3–12 years in both cohorts. Individuals were included in unmatched analyses and in co-twin control analyses with disease discordant twin pairs. Results Early-life antibiotic use was associated with increased risk of asthma (NTR OR 1.34, 95% CI 1.28–1.41; CATSS OR 1.45, 95% CI 1.34–1.56) and eczema (NTR OR 1.08, 95% CI 1.03–1.13; CATSS OR 1.07, 95% CI 1.01–1.14) in unmatched analyses. Co-twin analyses in monozygotic and dizygotic twin pairs showed similar results for asthma (NTR OR 1.54, 95% CI 1.20–1.98; CATSS OR 2.00, 95% CI 1.28–3.13), but opposing results for eczema in the NTR (OR 0.99, 95% CI 0.80–1.25) and the CATSS (OR 1.67, 95% CI 1.12–2.49). The risk of asthma increased for antibiotics prescribed for respiratory infections (CATSS OR 1.45, 95% CI 1.34–1.56), but not for antibiotics commonly used for urinary tract/skin infections (CATSS OR 1.02, 95% CI 0.88–1.17). Conclusion Children exposed to early-life antibiotic use, particularly prescribed for respiratory infections, may be at higher risk of asthma. This risk can still be observed when correcting for genetic and environmental factors. Our results could not elucidate whether the relationship between early-life antibiotic use and eczema is confounded by familial and genetic factors.
Abstract P155: Acute Stress From Elections and Hospitalization for Acute Myocardial Infarction
Authors: Matthew T Mefford, Murray A Mittleman, Bonnie Li, Lei Qian, Kristi Reynolds, Hui Zhou, Teresa N Harrison, Alan C Geller, Stephen Sidney, Richard P Sloan, Elizabeth Mostofsky, David R Williams
Journal: Circulation (2020)

Background: A growing body of evidence suggests that stressors are associated with heightened cardiovascular risk within hours after the triggering event, and stress from election campaigns is associated with a heightened risk of pre-term birth. Hypothesis: Potential stress from the 2016 presidential election was associated with an increased hospitalization rate for acute myocardial infarction (AMI) in the following week. Methods: Among active members 18 years of age and older in Kaiser Permanente Southern California, AMI was defined as an inpatient hospitalization with a primary discharge diagnosis of ICD-10-CM codes I21.x or I22.x. In an ecological analysis, we calculated relative risks (RR) and 95% confidence intervals (CI) comparing rates of AMI per 100,000 person-years (PY) within one week following the date of the 2016 presidential election (risk window) to rates in the prior two weeks (control window) overall and within subgroups by age, sex, and race/ethnicity. We repeated the above analysis comparing rates of AMI within one week of the 2016 election date to rates in the prior week. Results: Compared to the rates of MI in the two weeks before the 2016 election (171.6 per 100,000 PY), the rate of AMI hospitalization in the week following election day (242.2 per 100,000 PY) was 1.41 times higher (95% CI 1.14, 1.75). (Table) Heightened AMI risk after the 2016 election was also observed among adults 55-74 years of age (RR 1.47, 95% CI 1.10, 1.98), men (RR 1.54, 95% CI 1.17, 2.02), and white individuals (RR 1.52, 95% CI 1.12, 2.06). However, there was no evidence of heterogeneity across age, sex, or race/ethnicity groups (p-values 0.98, 0.30, and 0.65, respectively). Using a one-week control window, similar results were observed. Conclusion: Increased AMI rates among subsets of the population coincident with the 2016 election is consistent with published data suggesting that acute sociopolitical stress may have adverse health effects.