tbuckley/cabot-search huggingface dataset:
Abstract P044: Repeated Measurement of Insulin Sensitivity is Increasing the Precision of Incident Dyslipidemia Prediction Compared to Single Baseline Measurement: The Ansan-Ansung Community Cohort Study
Authors: Ju-mi Lee, Kyoung Min Kim, Soo Lim, Hyeon Chang Kim
Journal: Circulation (2019)

Introduction: Medical data are commonly measured repeatedly. However, there is a lack of studies of the usability of trajectory as a repeated measurement on the prediction model compare to the single measurement. Objectives: This study aimed to evaluate whether repeated measurement of insulin sensitivity can improve the prediction of incident dyslipidemia beyond the single measurement. Methods: Participants (n=3899; aged 40-69 years, during visit 1 to 7, mean follow-up 12 years) were recruited from the Ansan-Ansung cohort study, a subset of Korean Genome Epidemiology Study. Oral glucose tolerance test (OGTT) were measured at every visit with a 2 year interval. Matsuda index of each visit was calculated by the formula 10 4 /((GLU0xINS0xGLU60xINS60) 0.5 ). We used total seven times of OGTT (28 OGTT index) for trajectories. Latent mixture modeling was used to identify trajectories in Matsuda index for 12 years. We used tertiles of baseline Matsuda index for single measurement. Age, body mass index, alcohol drinking, cigarette smoking, c reactive protein, education level, and income were covariates. We compared two model’s discrminatory power using area under the curve of the receriver operating characteristics curve (AUROC). Results: In the trajectory model (repeated measurement), three distinct insulin sensitivity trajectories were identified: low-stable (Group 1; 88.8%), steady decreasing (Group 2; 9.7%), and fast decreasing (Group 3; 1.5%). In the baseline single measurement model, tertile groups were devided: low tertile(&lt;6.25, N=1306, 33.50%), tertile2 (6.25-10.89, N=1277, 32.75%), and tertile 3(≥10.89, N=1316, 33.75%). Trajectory model showed better discrimination power compared to single measurement model in the total population (AUROC 0.6303 vs. 0.6234) and men (AUROC 0.6671 vs. 0.6470) but not in women (AUROC 0.6171 vs. 0.6176). Conclusions: Repeated measurement of insulin sensitivity can improve the prediction of incident dyslipidemia in the general population.
Abstract P035: Habitual Aerobic Exercise-Induced Decrease in Circulating C1q Level is Associated With Reduction of Cardiovascular Diseases Risks in the Elderly
Authors: Natsuki Hasegawa, Naoki Horii, Shumpei Fujie, Masataka Uchida, Kiyoshi Sanada, Takafumi Hamaoka, Motoyuki Iemitsu
Journal: Circulation (2019)

Introduction: Habitual aerobic exercise leads to reduction of arterial wall thickness and arterial stiffness with aging. Recently, C1q has been identified as a novel myokine, and the expression of muscle C1q mRNA increases with aging. Additionally, in vivo and in vitro studies, C1q induces proliferation of vascular smooth muscle cells. However, it remains unclear whether the secretion of myokines, C1q, TNF-alpha and IL-6 are related to the changes in cardiovascular disease risk by aging and regular exercise. PURPOSE: This study aimed to clarify whether serum C1q, TNF-alpha and IL-6 levels are associated with the changes in cardiovascular disease risks with aging and regular aerobic exercise. Methods: In a cross-sectional study, 127 healthy male and female subjects (18-81 years) were enrolled in this study. Subjects were divided into two groups; young (&lt;40 year) and middle-aged and older (≥40 year) groups. Serum C1q, TNF-alpha, IL-6 levels were determined by ELISA. Risks of cardiovascular disease were estimated by using carotid-femoral pulse wave velocity (cfPWV) and common carotid intima-media thickness (ccIMT). Additionally, in an intervention study, thirteen older male subjects were randomly divided into two groups: aerobic training group (AT: n=6) and a sedentary control group (Con: n=7). subjects in the AT group completed 8 wk of aerobic exercise training (60-70% peak oxygen uptake for 45 min, 3 days/wk). Results: In the cross-sectional study, serum C1q, TNF-alpha and IL-6 levels, cfPWV and ccIMT were significantly higher in middle-aged and older group as compared with young group (respectively p&lt;0.05). Positive correlations between cfPWV and serum C1q (r=0.41, p&lt;0.05), TNF-alpha (r=0.28, p&lt;0.05) or IL-6 (r=0.26, p&lt;0.05) levels were seen. Additionally, ccIMT was positively correlated with only serum C1q (r=0.67, p&lt;0.05). After adjusting for TNF-alpha and IL-6, the association between the serum C1q and cfPWV (ß=0.44, p&lt;0.05) or ccIMT (ß=0.83, p&lt;0.05) remained statistically significant. Additionally, in the intervention study, cfPWV and serum C1q level significantly decreased after AT intervention (each P&lt;0.05). Furthermore, the AT-induced change in serum C1q level was positively correlated with AT-induced change in cfPWV (r=0.65, P&lt;0.05) and ccIMT (r=0.59, P&lt;0.05). Conclusion: These results suggest that circulating C1q level may reflect the changes of arterial stiffness and thickness with aging and regular exercise, and the reduction of serum C1q level in response to regular aerobic exercise may contribute to the reduction in cardiovascular disease risks in the elderly.
Novel Allosteric Inhibitors of Heat Shock Protein 70 As Agents to Probe Protein Homeostasis and Overcome Proteasome Inhibitor Resistance in Multiple Myeloma
Authors: Ian Ferguson, Christine Lam, Margarette C. Mariano, Donghui Wang, Paul Phojanakong, Sami Toumivaara, Hao Shao, Byron C Hann, Jason Gestwicki, Arun P Wiita
Journal: Blood (2018)
Abstract P247: Combination of Obesity and Metabolic Syndrome is Associated With Highest Rate of Depression Secondary to Increased Inflammation
Authors: Kasra Moazzami, Bruno Lima, Samaah Sullivan, Amit Shah, J. Douglas Bremner, Viola Vaccarino
Journal: Circulation (2019)

Introduction: A growing body of evidence suggests that obesity and metabolic syndrome (MetS) are associated with depression and that inflammation may play a role. However, the separate and combined associations of obesity and MetS on the prevalence of depression and their relationship with inflammation have not been investigated. Hypothesis: We hypothesized that the combination of obesity and MetS would be associated with the highest rates of both depression and elevated inflammation. Methods: Data were collected from the National Health and Nutrition Examination Survey between 2009 and 2014. Depression was assessed with the Patient Health Questionnaire-9 (PHQ-9) and was defined with a cut-point of ≥ 10. Obesity was defined as BMI ≥ 30 kg/m 2 . MetS was defined based on the American Heart Association consensus definition. Participants were divided into four groups: healthy normal weight, metabolically healthy obesity, metabolically unhealthy normal weight, and metabolic unhealthy obese (MUO). C-reactive protein was assessed in a subsample. Results: Participants with MUO had the highest prevalence of depression compared to the healthy group (14.8% vs 6.8, P&lt;0.001). The mean PHQ-9 score was also highest among the MUO group (4.16 ± 0.09). While both obesity and MetS were independently associated with depression, there was a significant interaction between the two (P&lt;0.001, Figure). On adjusted analysis, the MUO group had the highest odds of depression (Figure). The MUO group also showed the highest geometric mean levels of C-reactive protein compared to the healthy group (0.34 ± 0.03 vs 0.11 ± 0.03, P&lt;0.001). Levels of C-reactive protein mediated the effect between MUO and depressive symptoms (80.5% of the total effect). Conclusion: Both obesity and MetS are associated with depression independent of each other, but participants with both conditions have the highest odds of depression. These findings underscore the importance of cardiometabolic disturbances as correlates of mental health status.
Clinical risk-based associations of lymph node dissection and detection of metastasis among men treated with radical prostatectomy.
Authors: Alejandro Abello, Patrick Aloysius Kenney, Michael Leapman
Journal: Journal of Clinical Oncology (2019)

284 Background: Pelvic lymph node dissection (PLND) is recommended for most men at risk for lymph node involvement at the time of radical prostatectomy (RP) yet is frequently omitted. We aimed to examine the probability of PLND based on clinical risk status, and evaluate the impact of increasing lymph node yield on cancer detection rate across risk strata. Methods: We queried the National Cancer Database from 2004 to 2014 to identify patients with clinically localized PCa who underwent RP as their primary treatment. We extracted patient clinical and sociodemographic variables. Risk status was assessed using UCSF Cancer of the Prostate Risk Assessment (CAPRA) score. We fit conditional logistic regression models to estimate likelihood of PLND and incremental value of increasing lymph node count by risk strata. Results: We identified 698,728 men with PCa treated with RP including 380.201 (54.41%) whit PLND. Mean age at diagnosis was 62.6. PLND was omitted (Nx) in 56.1% of patients with low CAPRA-risk disease, 31.44% with intermediate and 24.72% high. Proportion of patients with &gt;30 lymph nodes removed decreased from 9.3% on 2004 to 3.64% on 2014. Adjusting for clinical and pathologic factors, treatment in a community versus academic (Odds Ratio, OR=1.62, 95% CI 1.59-1.66; P &lt;0.001) and black race (OR=1.13, 95% CI 1.09-1.17, P: 0.01) was associated with pNx status. Increasing lymph node count was independently associated with greater likelihood of detection of lymph node metastasis in all risk strata (11-20 nodes: OR: 3.13 , 95% CI 2.90-3.37, P&lt;0.001; 20-30 nodes: OR: 5.07 , 95% CI 4.50-5.73, P&lt;0.001; &gt;30 nodes OR: 6.58, 95% CI 5.38-8.05, P&lt;0.001) including patients with CAPRA-0 (11-20 nodes: OR: 3.28 , 95% CI 3.06-3.53, P&lt;0.001; 20-30 nodes: OR: 5.77, 95% CI 5.16-6.45, P&lt;0.001; &gt;30 nodes OR: 7.90, 95% CI 6.56-9.51, P&lt;0.001). Conclusions: PLND continues to be omitted in a substantial proportion of intermediate and high risk patients. Increasing lymph node yield was associated with greater odds of detecting lymph node metastasis in all groups of patients, including those at the lowest level of risk by clinical criteria.
Calcimimetics maintain bone turnover in uremic rats despite the concomitant decrease in parathyroid hormone concentration
Authors: Juan M. Díaz-Tocados, María E. Rodríguez-Ortiz, Yolanda Almadén, Carmen Pineda, Julio M. Martínez-Moreno, Carmen Herencia, Noemi Vergara, M. Victoria Pendón-Ruiz de Mier, Rafael Santamaría, Cristian Rodelo-Haad, Antonio Casado-Díaz, Víctor Lorenzo, Catarina Carvalho, João M. Frazão, Arnold J. Felsenfeld, William G. Richards, Escolástico Aguilera-Tejero, Mariano Rodríguez, Ignacio López, Juan R. Muñoz-Castañeda
Journal: Kidney International (2019)

Calcimimetics decrease parathyroid hormone (PTH) secretion in patients with secondary hyperparathyroidism. The decrease in PTH should cause a reduction in bone turnover; however, the direct effect of calcimimetics on bone cells, which express the calcium-sensing receptor (CaSR), has not been defined. In this study, we evaluated the direct bone effects of CaSR activation by a calcimimetic (AMG 641) in vitro and in vivo. To create a PTH "clamp," total parathyroidectomy was performed in rats with and without uremia induced by 5/6 nephrectomy, followed by a continuous subcutaneous infusion of PTH. Animals were then treated with either the calcimimetic or vehicle. Calcimimetic administration increased osteoblast number and osteoid volume in normal rats under a PTH clamp. In uremic rats, the elevated PTH concentration led to reduced bone volume and increased bone turnover, and calcimimetic administration decreased plasma PTH. In uremic rats exposed to PTH at 6-fold the usual replacement dose, calcimimetic administration increased osteoblast number, osteoid surface, and bone formation. A 9-fold higher dose of PTH caused an increase in bone turnover that was not altered by the administration of calcimimetic. In an osteosarcoma cell line, the calcimimetic induced Erk1/2 phosphorylation and the expression of osteoblast genes. The addition of a calcilytic resulted in the opposite effect. Moreover, the calcimimetic promoted the osteogenic differentiation and mineralization of human bone marrow mesenchymal stem cells in vitro. Thus, calcimimetic administration has a direct anabolic effect on bone that counteracts the decrease in PTH levels.
Evaluation of submicron particle docetaxel directly injected into uro-oncologic xenografts.
Authors: Gere Dizerega, Holly Maulhardt, Lauren M Peterson, Michael Frost, Ashley Tornio, Sara Dafoe, Leanne Drummond
Journal: Journal of Clinical Oncology (2019)

360 Background: We evaluated intratumoral (IT) injection of submicron particles of pure docetaxel (NanoDoce) into clear cell renal carcinoma (768-O [R]), transitional cell bladder carcinoma (UM-UC-3 [B]) and prostate carcinoma (PC-3 [P]) xenografts implanted into immunocompromised rats and mice. Methods: Animals received IT NanoDoce and IV docetaxel per Table. Treatments were 7 days apart. Animals were followed up to 60 days post-treatment initiation. Tumor size, clinical signs and body weight were assessed 2-3 times per week. In the 786-O and UM-UC-3 studies, tumor site tissues were analyzed for docetaxel levels and H&amp;E and IHC (CD11b, CD45r) was evaluated. Results: Tumor volume decreases with 2 and 3 doses of NanoDoce were significantly greater than (R, B) or similar (P) to IV docetaxel and better than vehicle (p &lt; 0.05). High tissue levels of docetaxel were detected in all NanoDoce-treated animals with evaluable tumor tissue. In these animals, histology confirmed tumor volume findings; IHC showed (peri)tumor-infiltrating immune cells in all NanoDoce-treated animals. Comparators exhibited limited to no infiltration. NanoDoce-treated UM-UC-3 tumor injection sites were typically cleared of tumor and contained lymphoid structures. No lymphoid structures were seen in comparators and all had residual tumor. Conclusions: Local presence of persistent, therapeutic levels of docetaxel from IT NanoDoce creates a unique disruption of the tumor microenvironment. IT injection of NanoDoce may kill tumor cells through direct and indirect means. NanoDoce directly inhibits tumor cell mitosis, and in reducing tumor burden, indirectly promotes immune cell-mediated tumor clearance. Clinical testing of NanoDoce in urogenital tumors is underway. [Table: see text]
Abstract 029: Cardiovascular Health and Cognitive Decline in Older Adults: The Cardiovascular Health Study
Authors: Kristine MaWhinney, Mamadou D Tounkara, Kirsten Evans, Emily Startup, Alexa Ehlert, Emarie Covey, Jordan Westra, Natalie J Blades, Mandip S Dhamoon, Hector M Gonzalez, Fumiaki Imamura, Elzbieta Kuzma, David J Llewellyn, M Lelinneth B Novilla, Monica Scrobotovici, W T Longstreth, Evan L Thacker
Journal: Circulation (2019)

Objective: The AHA Life’s Simple 7 (LS7) defines cardiovascular health with smoking, physical activity, diet quality, body mass index (BMI), blood pressure, total cholesterol, and blood glucose. We examined associations of LS7 score and its components with cognitive decline in older adults. Methods: The Cardiovascular Heart Study is a longitudinal cohort of 5,888 adults aged 65 and above. We analyzed 4,165 who had LS7 score measured at baseline (1989), complete covariate data, and at least one Modified Mini-Mental State Examination (3MS) score during follow-up (through 1998). We scored each LS7 component as ideal (2), intermediate (1), or poor (0), summed all components to a total LS7 score ranging from 0 (worst) to 14 (best), and categorized total LS7 score as ideal (10-14), intermediate (5-9), or poor (0-4). 3MS is a measure of global cognition ranging from 0 (worst) to 100 (best) and was obtained annually during a mean follow-up of 6.8 years. Using linear mixed models, we estimated associations of LS7 score and its components with annual rate of cognitive decline, adjusted for demographic, behavioral, and clinical factors. Results: In adjusted models, mean annual decline in 3MS score was 0.83 points (95% CI: 0.61, 1.04) for those with poor LS7 scores at baseline, 0.63 points (95% CI: 0.59, 0.67) with intermediate scores, and 0.42 points (95% CI: 0.37, 0.47) with ideal scores (p &lt; 0.0001 for difference in mean annual decline across LS7 categories). Better physical activity, diet quality, blood pressure control, and blood glucose control were all associated with slower cognitive decline (Table). BMI, however, was opposite, with obesity (poor) associated with slower decline, and normal weight (ideal) associated with faster decline (p &lt;0.0001). Conclusions: Better cardiovascular health measured by LS7 in old age is associated with slower average cognitive decline. The role of BMI as a component of LS7 in older adults may warrant reconsideration, as lower BMI in late-life may represent frailty and increased risk for cognitive decline.
Performance of the 17-gene genomic prostate score test in men with prostate cancer (PCa) managed with active surveillance (AS): Results from the Canary Prostate Active Surveillance Study (PASS).
Authors: Daniel W. Lin, Yingye Zheng, Jesse McKenney, Marshall Brown, Ruixiao Lu, Michael Crager, Hilary Boyer, James D. Brooks, Atreya Dash, Michael Fabrizio, Martin Gleave, Michael A. Liss, Todd Matthew Morgan, Ian M Thompson, Andrew Wagner, Athanasios Tsiatis, Andrea Pingatore, H. Jeffrey Lawrence, Peter S Nelson, Lisa F Newcomb
Journal: Journal of Clinical Oncology (2019)

262 Background: The 17-gene Genomic Prostate Score (GPS) test (scale 0-100) predicts adverse surgical pathology (AP) and recurrence in newly diagnosed low- and intermediate-risk PCa. Studies of the predictive value of the GPS test in men initially managed with AS are limited. Methods: Diagnostic biopsy tissue was obtained from 634 men enrolled at 8 sites in PASS. Time to AP (Gleason Grade Group (GG) ≥3, ≥pT3a, or N1) in men who underwent radical prostatectomy (RP) was the primary endpoint. All diagnostic biopsies and RP specimens were centrally reviewed. Multivariate regression models for interval censored data were used to evaluate the association between time to AP and GPS. Inverse probability of censoring weighting was applied to adjust for informative censoring. Association between GPS and time to Gleason score upgrade on surveillance biopsy was also evaluated using a Cox Proportional Hazards model. Results: GPS results were obtained for 432 men (median follow-up 4.6 [IQR: 2.9-6.2] years); 374 and 58 with GG 1 or 2 cancer, respectively; median PSA density (PSAD) was 0.11 [IQR: 0.08-0.15]; 101 men underwent RP with central pathology after a median of 2.1 [IQR: 1.3-4.3] years surveillance, and 52 (52%) men undergoing RP had AP. 167 men upgraded at a subsequent biopsy. No clinico-pathologic covariates were significantly associated with AP other than PSAD. GPS was significantly associated with time to AP (hazards ratio [HR]/20 GPS units: 1.96 [95% CI = 1.17-4.28]; p = 0.030), when adjusted for diagnostic GG, or for dichotomous PSAD ( &lt; vs ≥ 0.15; HR: 1.83, 95% CI = 1.04-3.62; p = 0.046). GPS was not significantly associated with AP (HR: 1.61, 95% CI = 0.87-2.98; p = 0.12) when adjusted for continuous PSAD. No association, either univariable or multivariable, was observed between GPS and subsequent biopsy upgrade. Conclusions: In a cohort of men on AS, GPS was associated with time to AP when adjusted for diagnostic GG or dichotomous PSAD. GPS was not associated with surveillance biopsy GG upgrading or AP at surgery after adjustment for continuous PSAD, although a trend was seen for AP, suggesting an association may be seen in a larger study.
Abstract P198: Why is the 10-Year-ASCVD Risk Higher in Elevated Blood Pressure Group Than Stage-1 Hypertension Group Among Korean Population?
Authors: Yongwoo Jeon, Ho Kyou Lee, Hyeon Chang Kim
Journal: Circulation (2019)

Introduction: New guidelines in 2017 by ACC/AHA for evaluation of high blood pressure could be applied to Korean population. However, 10-year-ASCVD risk was higher in the people with elevated blood pressure(EBP) than with stage-1 hypertension(ST1) in Korea. Methods: We analyzed 53,746 Korean adults aged over 19 years from the each period section of Korea National Health and Nutrition Examination Survey in 10 years(IV(07’-09’), V(10’-12’), VI(13’-15’) and VII(16’)). The 10-year-ASCVD risk was calculated by using Pooled Cohort Equation modified for Korean population, and blood pressure categories by the new guideline were classified. We also compared the variables(age, total cholesterol, HDL-cholesterol, SBP, smoking, diabetes) of the equation for each blood pressure categories. Results: Mean 10-year-ASCVD risk was higher in EBP than in ST1. (7.0±0.5 vs 4.2±0.2 in VII; 6.3±0.3 vs 3.9±0.1 in VI; 5.7±0.3 vs 3.9±0.3 in V; 6.5±0.4 vs 3.8±0.1 in IV, EBP vs ST1 respectively) When comparing the variables in the equation, mean SBP was higher in EBP than ST1 among men, whereas mean age was higher in EBP than ST1 among women. Among ST1, those who have high diastolic blood pressure but without high systolic blood pressure was 74.0%(95%CI 69.8-78.1) in men. Conclusion: Higher 10-year-ASCVD risk in EBP could result from higher SBP than ST1 in men due to people with high DBP without high SBP in ST1, whereas higher age in women among Korean population.
Detection in the United Kingdom of the Neisseria gonorrhoeae FC428 clone, with ceftriaxone resistance and intermediate resistance to azithromycin, October to December 2018
Authors: David W Eyre, Katy Town, Teresa Street, Leanne Barker, Nicholas Sanderson, Michelle J Cole, Hamish Mohammed, Rachel Pitt, Maya Gobin, Charles Irish, Daniel Gardiner, James Sedgwick, Charles Beck, John Saunders, Deborah Turbitt, Clare Cook, Nick Phin, Bavithra Nathan, Paddy Horner, Helen Fifer
Journal: Eurosurveillance (2019)

We describe detection in the United Kingdom (UK) of the drug-resistant Neisseria gonorrhoeae FC428 clone, with ceftriaxone resistance and intermediate azithromycin resistance. Two female patients developed infection following contact with UK-resident men from the same sexual network linked to travel to Ibiza, Spain. One case failed treatment with ceftriaxone, and azithromycin and gentamicin, before successful treatment with ertapenem. Both isolates had indistinguishable whole-genome sequences. Urgent action is essential to contain this drug-resistant strain.
Discussing Prognosis, Preferences, and End-of-Life Care in Advanced Cancer
Authors: Belinda E. Kiely, Martin R. Stockler
Journal: JAMA Oncology (2019)

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