tbuckley/cabot-search huggingface dataset:
Potential Impact of Cessation Interventions at the Point of Lung Cancer Screening on Lung Cancer and Overall Mortality in the United States
Authors: Pianpian Cao, Jihyoun Jeon, David T. Levy, Jinani C. Jayasekera, Christopher J. Cadham, Jeanne S. Mandelblatt, Kathryn L. Taylor, Rafael Meza
Journal: Journal of Thoracic Oncology (2020)
Author Correction: Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1
Authors: Michael D. Crowther, Garry Dolton, Mateusz Legut, Marine E. Caillaud, Angharad Lloyd, Meriem Attaf, Sarah A. E. Galloway, Cristina Rius, Colin P. Farrell, Barbara Szomolay, Ann Ager, Alan L. Parker, Anna Fuller, Marco Donia, James McCluskey, Jamie Rossjohn, Inge Marie Svane, John D. Phillips, Andrew K. Sewell
Journal: Nature Immunology (2020)
Abstract P319: Racial Differences and Temporal Trends in Obesity Among Patients Hospitalized With Acute Decompensated Heart Failure With Preserved Ejection Fraction: The ARIC Study Community Surveillance
Authors: Melissa C Caughey, Muthiah Vaduganathan, Sameer Arora, Arman Qamar, Robert J Mentz, Patricia Chang, Stuart D Russell, Sanjiv J Shah, Wayne D Rosamond, Ambarish Pandey
Journal: Circulation (2020)

Introduction: Obesity is disproportionately prevalent in black populations and strongly associated with heart failure with preserved ejection fraction (HFpEF). An “obesity paradox” or lower mortality risk with obesity, has been reported in HFpEF populations. Whether racial differences exist in the temporal trends and outcomes of obesity is uncertain. Methods: Hospitalizations for acute decompensated heart failure (ADHF) were sampled from 2005-2014 by the ARIC Study Community Surveillance and classified by physician review. BMI was calculated using the admission height and weight. Associations between obesity and 1-year all-cause mortality were analyzed with multivariable Cox regression. Results: There were 10,147 weighted hospitalizations for ADHF with ejection fraction ≥50% (64% female, 74% white). Overall, black patients had a higher mean BMI than white patients (34 vs. 30 kg/m 2 ; P &lt;0.0001), and a greater prevalence of obesity (56% vs. 43%; P &lt;0.0001). Mean BMI and obesity steadily increased from 2005-2014 for white patients (Trends: P = 0.003 and P = 0.002) while remaining stable for black patients. Within BMI groups (18.5-24, 25-30, 30-35, 35-40, and ≥40 kg/m 2 ) a U-shaped mortality risk was observed, with the lowest risk among patients with a BMI of 30-35 kg/m 2 ( Figure ). When defining obesity by a BMI cutpoint ≥30 kg/m 2 , the “obesity paradox” was apparent in 2005-2009 for white obese vs. non-obese patients (HR = 0.58, 95% CI: 0.38 - 0.80), but attenuated by 2010-2014 (HR = 1.11; 95% CI: 0.80 - 1.48); P for interaction =0.006. Among black patients, there was no survival benefit for a BMI ≥30 kg/m 2 in 2005-2009 (HR = 1.15; 95% CI; 0.65 - 2.02) or 2010-2014 (HR = 1.06; 95% CI: 0.68 - 1.66). Conclusion: In this decade-long community surveillance of HFpEF patients hospitalized with ADHF, obesity and mean BMI were stable for black patients but steadily increased for white patients. A BMI ≥30 kg/m 2 was initially associated with better survival among white patients but the association dissipated as obesity and mean BMI increased over time.
Abstract P440: Diabetes and the Long-term Risk of Abdominal Aortic Aneurysm: The Atherosclerosis Risk in Communities Study
Authors: Kunihiro Matsushita
Journal: Circulation (2020)

Introduction: Diabetes mellitus is known to be related to lower risk of abdominal aortic aneurysm (AAA). However, the full spectrum of glycemic status including prediabetes and the duration of diabetes have not been extensively investigated in the context of AAA risk. Methods: We prospectively studied incident AAA (defined using outpatient records, hospitalization discharge, or death certificate) according to the baseline glycemic status defined using physician diagnosed diabetes, self-reported anti-diabetic medication use and glucose or hemoglobin A1c (diabetes, pre-diabetes, vs. normal glycemia) in 13,116 participants (1990-1992) and the time-varying exposure of duration of incident diabetes in 11,675 participants (1987-1989) using Cox models. We cross-sectionally explored ultrasound-based abdominal aortic diameter by glycemic status and cumulative duration of diabetes in 4,710 participants (2011-2013) using linear regression models. Results: There were 489 incident AAA cases during a median follow-up of ~20 years. Diabetes but not pre-diabetes (vs. normal glycemia) at baseline was independently associated with lower risk of AAA (HR: 0.71 [95%CI 0.51 - 0.99]). The association was largely driven by long-standing diabetes (≥10 years duration: HR: 0.58 [95%CI 0.38 - 0.87]). Longer duration of diabetes was associated with lower risk of AAA (Figure 1A), with 30-50% lower risk in 8 years after incident diabetes diagnosis, as well as smaller aortic diameter measured cross-sectionally (Figure 1B) compared to non-diabetes. Pre-diabetes consistently showed relatively greater diameter (e.g., +0.26 mm [-0.03, +0.54]). Conclusions: Diabetes (but not prediabetes) and its longer duration were independently associated with lower risk of AAA and smaller aortic diameter. Our findings suggest that the cumulative effects of hyperglycemia may play a role in the counterintuitively lower AAA risk. Reduced aortic diameter might be a structural mechanism of decreased AAA risk in diabetes. Figure 1A. Adjusted hazard ratio of incident AAA according to the duration of diabetes among incident cases as a time-varying exposure; Figure 1B. Adjusted difference in maximum diameter (mm) for diabetes vs. non-diabetes by cumulative duration of diabetes. Both models adjusted for age, sex, race, education, BMI, height, total cholesterol, HDL cholesterol, systolic blood pressure, diastolic blood pressure, anti-hypertensive medication, cholesterol-lowering medication, cigarette smoking pack-years, alcohol drinking, eGFR, prevalent peripheral artery disease, prevalent coronary heart disease, and prevalent stroke (time-varying covariates for Figure 1A and baseline covariates for Figure 1B).
Abstract 09: The Health Freedom Path to Wellness Program: A Novel Educational and Behavioral Intervention to Promote Cardiovascular Health Equity
Authors: Tanjala S Purnell, Ina Glenn-Smith, Sunjae Bae, Grecia Vargas, Anika L Hines, Jeanne Charleston
Journal: Circulation (2020)

Background: African Americans (AAs) and adults living in urban communities continue to experience disproportionately high rates of cardiovascular disease (CVD) and associated risk factors (e.g., hypertension, diabetes, obesity) despite decades of recognition of these disparities. Methods: The Health Freedom Path to Wellness Program is an innovative community-based educational and behavioral intervention to reduce disparities in CVD risk factors. The goal of this study was to test the effectiveness of the Circle of Friends (COF) educational and social support component of the Health Freedom intervention. The Health Freedom-COF incorporated six weekly one-hour long sessions led by lay health workers trained in CVD health education based on the AHA’s Simple 7 guidelines, blood pressure (BP) measurement, physical activity, and behavior change strategies, and culminated in a 5K celebration walk that gives participants an opportunity to learn about Maryland’s important role in the Underground Railroad. Results: Study participants included 353 adults in Maryland (93% AAs, mean age: 53 years; 85% female; and 35% with annual incomes &lt;$50,000). At baseline, mean BP(SD) was 127.4 (17.6)/77.1 (10.8) mmHg; mean weight in pounds (SD) was 191.6 (45.2); 43.1% had diagnosed hypertension, and 15.0% had diabetes. Compared with their pre-intervention assessments, adults who completed the intervention experienced an average reduction of -5.2 mm Hg systolic blood pressure (95% CI: 4.1-6.3, p&lt;0.001) and -3.3 mm Hg diastolic BP (95% CI: 2.5-4.1, p&lt;0.001). At baseline, only 3.3% of participants reported a weekly consumption of 5+ fruit servings; 5.9% reported 5+ vegetable servings, and 12.8% reported 5+ days of physical activity. However, after completing the program, 22.4% of participants reported a weekly consumption of 5+ fruit servings; 28.6% reported 5+ vegetable servings, and 46.7% reported 5+ days of physical activity. Conclusions: The Health Freedom educational and behavioral intervention was associated with improvements in blood pressure, diet, and physical activity among socially at-risk adults.
Direct Binding to NLRP3 Pyrin Domain as a Novel Strategy to Prevent NLRP3‐Driven Inflammation and Gouty Arthritis
Authors: Gabsik Yang, Hye E. Lee, Su‐Jin Moon, Kyung M. Ko, Jung H. Koh, Jin K. Seok, Jun‐Ki Min, Tae‐Hwe Heo, Han C. Kang, Yong‐Yeon Cho, Hye S. Lee, Katherine A. Fitzgerald, Joo Y. Lee
Journal: Arthritis & Rheumatology (2020)

Objective The NLRP 3 inflammasome is closely linked to the pathophysiology of a wide range of inflammatory diseases. This study was undertaken to identify small molecules that directly bind to NLRP 3 in order to develop pharmacologic interventions for NLRP 3‐related diseases. Methods A structure‐based virtual screening analysis was performed with ~62,800 compounds to select efficient NLRP 3 inhibitors. The production of caspase 1‐p10 and interleukin‐1β ( IL ‐1β) was measured by immunoblotting and enzyme‐linked immunosorbent assay to examine NLRP 3 inflammasome activation. Two gouty arthritis models and an air pouch inflammation model induced by monosodium urate monohydrate ( MSU ) crystal injection were used for in vivo experiments. Primary synovial fluid cells from gout patients were used to determine the relevance of NLRP 3 inflammasome inhibition in human gout. Results Beta‐carotene (provitamin A) suppressed the NLRP 3 inflammasome activation induced by various activators, including MSU crystals, in mouse bone marrow–derived primary macrophages ( P &lt; 0.05). Surface plasmon resonance analysis demonstrated the direct binding of β‐carotene to the pyrin domain ( PYD ) of NLRP 3 ( K D = 3.41 × 10 −6 ). Molecular modeling and mutation assays revealed the interaction mode between β‐carotene and the NLRP 3 PYD . Inflammatory symptoms induced by MSU crystals were attenuated by oral administration of β‐carotene in gouty arthritis mouse models ( P &lt; 0.05), correlating with its suppressive effects on the NLRP 3 inflammasome in inflamed tissues. Furthermore, β‐carotene reduced IL ‐1β secretion from human synovial fluid cells isolated from gout patients ( P &lt; 0.05), showing its inhibitory efficacy in human gout. Conclusion Our results present β‐carotene as a selective and direct inhibitor of NLRP 3, and the binding of β‐carotene to NLRP 3 PYD as a novel pharmacologic strategy to combat NLRP 3 inflammasome–driven diseases, including gouty arthritis.
Abstract P432: Racial Differences In Endothelial Function And Insulin Sensitivity
Authors: Catharine Couch, Nikki Bush, Tanja Dudenbostel, Barbara Gower
Journal: Circulation (2020)

Racial disparities in health outcomes continue to be a significant public health concern and African Americans (AA) are disproportionately burdened by several risk factors for cardiovascular disease. Endothelial dysfunction has been shown to be a predictor of CVD and metabolic factors, including insulin resistance, are associated with endothelial dysfunction. Compared to EA, AA have impaired endothelial function and are more insulin resistant (less insulin sensitive). However, it remains unclear how insulin resistance may contribute to endothelial dysfunction in AA and EA. The purpose of the present study was to evaluate the relationship between insulin sensitivity and endothelial function in AA and EA. It was hypothesized that insulin sensitivity would be associated with endothelial function in both AA and EA. Skeletal muscle insulin sensitivity was measured by hyperinsulinemic-euglycemic glucose clamp technique in 112 lean, overweight, and obese AA and EA adults without diabetes. Insulin was infused at 120 mU/m 2 /min for 3 hours and an infusion of 20% dextrose was adjusted to maintain blood glucose at the fasting level. Insulin sensitivity (10 -4 .dL.kg -1 .min -1 /(μU/mL)) was defined as M/(G x ΔI), where M is steady state glucose infusion rate, G is steady state serum glucose concentration, and ΔI is the difference between basal and steady state serum insulin concentrations. M was adjusted for total lean body mass which was measured by dual-energy X-ray absorptiometry (DXA). Endothelial function was assessed by percent change in flow-mediated brachial artery dilatation (FMD). Changes in brachial artery diameter during reactive hyperemia were measured using ultrasound. Increased blood flow was induced via blood pressure cuff around the forearm, with a 5-minute inflation at 50 mmHg above the subject’s systolic blood pressure. Brachial arterial flow was determined using a pulsed-Doppler signal at baseline and 10-15 seconds after cuff release. Arterial diameter was measured at end-diastolic phase from super-VHS recordings. For reactive hyperemia response, measurements with the 5 largest diameters were averaged and the percent increase from baseline was determined as FMD. A total of 55 AA and 57 EA were included in the analysis. Mean insulin sensitivity was 4.89 in AA and 7.97 in EA (p &lt; .0001) and mean FMD was 10.69 in AA and 10.14 in EA (p = .595). Linear regression analysis indicated a significant relationship between insulin sensitivity and endothelial function in AA but not in EA (p= .005 and p= .5, respectively). These results suggest that insulin sensitivity may play a role in determining endothelial function in AA.
Knowing what’s growing: Why ductal and intraductal prostate cancer matter
Authors: Mitchell G. Lawrence, Laura H. Porter, David Clouston, Declan G. Murphy, Mark Frydenberg, Renea A. Taylor, Gail P. Risbridger
Journal: Science Translational Medicine (2020)

IDC-P and ductal adenocarcinoma are two pathologies that can indicate aggressive primary prostate cancer.
The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application
Authors: Stephen A. Lauer, Kyra H. Grantz, Qifang Bi, Forrest K. Jones, Qulu Zheng, Hannah R. Meredith, Andrew S. Azman, Nicholas G. Reich, Justin Lessler
Journal: Annals of Internal Medicine (2020)

A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019. There is limited support for many of its key epidemiologic features, including the incubation period for clinical disease (coronavirus disease 2019 [COVID-19]), which has important implications for surveillance and control activities.
Abstract 15199: Noninvasive Micro-Ultrasound Imaging of Heart-Brain Interaction via mTOR Pathway in Experimental Subarachnoid Hemorrhage
Authors: Kazumasu Sasaki, Tatsushi Mutoh, Shuzo Yamamoto, Yukiko Yamamoto, Yoshiharu Tsuru, Yasuyuki Taki, Ryuta Kawashima
Journal: Circulation (2018)

Introduction: Subarachnoid hemorrhage (SAH) can cause various neurogenic cardiovascular complications such as Takotsubo cardiomyopathy. Mammalian target of rapamycin (mTOR) signalling may play an i...
Abstract P153: Multiple Vulnerabilities to Health Disparities and Incident Heart Failure in the Reasons for Geographic and Racial Differences in Stroke Study
Authors: Laura C Pinheiro, Evgeniya Reshetnyak, Madeline R Sterling, Emily B Levitan, Monika M Safford, Parag Goyal
Journal: Circulation (2020)

Background: Multiple socially determined vulnerabilities (SDV) to health disparities often cluster within the same individual. Previous studies have shown that SDV are separately associated with increased risk of heart failure (HF). As there may be a cumulative effect of these SDVs in the same individual, understanding their joint impact on the incidence of HF is critical. Methods: REGARDS is a national prospective cohort study that recruited 30,239 adults &lt;45 years of age from 2003-2007 with ongoing follow-up. We followed participants free of HF at baseline for incident HF hospitalization through December 31, 2016. Guided by the Healthy People 2020 framework, we examined 10 potential SDVs, retaining those that were associated with incident HF (p&lt;0.10) and creating a count of SDV (0, 1, 2, 3+). We used Cox models to examine associations between the SDV count and incident HF, adjusting for potential confounders. Since disparities in HF have been shown to be greatest in younger individuals models were stratified by age. Results: The 25,790 participants were followed for a median of 10.1 years (IQR 6.5, 11.9); their mean age at baseline was 64.8, 55%% were women, and 40% were blacks. In age-adjusted models, Black race, low educational attainment, low annual household income, zip code poverty, poor public health infrastructure, and lack of health insurance were significantly associated with incident HF. In fully adjusted models, among those 45-64 years, compared to having no SDV, having a SDV was significantly associated with incident HF, with a trend toward a higher count conferring greater risk (Fig. 1). There was no association in other age groups. Conclusions: An increased number of SDVs was associated with risk of incident HF hospitalization among adults &lt;65 years, even after adjustment for cardiovascular risk factors. Using a simple count of SDVs that could be incorporated into the social history during clinical assessment may identify younger individuals at increased risk of incident HF.
Treatment of advanced AIDS-associated Kaposi sarcoma in resource-limited settings: a three-arm, open-label, randomised, non-inferiority trial
Authors: Susan E Krown, Carlee B Moser, Patrick MacPhail, Roy M Matining, Catherine Godfrey, Stephanie R Caruso, Mina C Hosseinipour, Wadzanai Samaneka, Mulinda Nyirenda, Naftali W Busakhala, Fred M Okuku, Josphat Kosgei, Brenda Hoagland, Noluthando Mwelase, Vincent O Oliver, Henriette Burger, Rosie Mngqibisa, Mostafa Nokta, Thomas B Campbell, Margaret Z Borok, Agnes Moses, Cecilia Kanyama, Pamela Mukwekwerere, Ivy Gudza, Felluna Chauwa, Godwin Ulaya, Irene Kutto, Priscilla Cheruiyot, Clement Okello, Annet Nakaganda, Geoffrey Koskei, Winnie Keter, Juliana Netto, Tamiris Baião, Iveshni Govender, Jessica O'Connell-Maritz, Kevin Cain, John Okanda, Lynne Cornelissen, Marije Van Schalkwyk, Rejoice Sikhosana, Minenhle Ngcobo, Jeannette Y. Lee, Taylor Harrison, William Wachsman, Katherine Shin, Scott Evans, Jennifer Rothenberg, Lara Hosey, Sean McCarthy, Otoniel Martinez-Maza, Charles Rinaldo, Dirk Dittmer, Charles Rinaldo, Courtney Fletcher, Michelle Rudek, Aida Asmelash, Valery Hughes, Jeffrey Schouten, David Shugarts, Tapiwanashe Kujinga, Amanda Zadzilka, Fredrick Kerui, Debora Robertson, James Rooney, Krishna Sewal, Brian Gottshall
Journal: The Lancet (2020)
カースルマン病患者から検出した抗CD3抗体に対する抗イディオタイプ抗体:エイズ関連疾病としての臨床的相関 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Tatsumi T, Shimada T, Sano T, Kimura H, Horiuchi F, Maeda Y, Kanamaru A
Journal: Blood (1998)
Comparison of quality-adjusted survival in patients with advanced renal cell carcinoma receiving first-line treatment with temsirolimus (TEMSR) or interferon-α (IFN) or the combination of IFN+TEMSR
Authors: S. Parasuraman, G. Hudes, D. Levy, A. Strahs, L. Moore, R. DeMarinis, A. S. Zbrozek
Journal: Journal of Clinical Oncology (2007)

5049 Background: In a phase 3, randomized, 3-arm study of TEMSR or IFN or the combination of TEMSR + IFN in the first-line treatment of patients with advanced renal cell carcinoma (RCC) and poor-prognostic features, TEMSR improved overall survival (p=0.0069) and progression-free survival (p=0.0001) vs. IFN (Hudes et al. J Clin Oncol. 2006;24:LBA4). Quality-adjusted survival was a pre-defined endpoint and is reported. Methods: Quality-adjusted time without symptoms and toxicity (QTWiST) was estimated by partitioning overall survival into 3 distinct health states: time with serious toxicity, time with progression, and time without symptoms and toxicity (TWiST). Survival was value-weighted when patients completed quality of life questionnaires (EQ-5D) at weeks 12 and 32, when a grade 3 or 4 adverse event (AE) was reported, upon relapse or progression, or upon withdrawal from the study. Treatment group comparisons used restricted means analyses estimated from censored survival data. Restricted means were computed for duration of each health state by truncating data at median follow-up (17.9 months). Variance and covariance were estimated using bootstrap methods. Results: All 626 randomized patients in the study were included in computation of health state durations. EQ-5D questionnaires were obtained from 260/300 (87%) upon progression and 230/570 (40%) after a grade 3/4 AE. Patients receiving TEMSR alone had 38% greater TWiST than those receiving IFN alone (TEMSR=6.5 months vs. IFN=4.7 months, p=0.00048). There was no significant difference in TWiST between the combination arm and IFN alone (IFN+TEMSR=5.4 months vs. IFN=4.7 months, p=0.1288). Patients receiving TEMSR alone had 23% greater Q-TWiST than those receiving IFN alone (TEMSR=7.0 months vs. IFN=5.7 months; p=0.0015). There was no significant difference in Q-TWiST for the combination arm compared with IFN alone (IFN+TEMSR=6.1 months vs. IFN=5.7 months, p=0.3469). Conclusions: Patients with advanced RCC receiving TEMSR alone had significantly greater quality-adjusted survival than those receiving IFN alone. No significant financial relationships to disclose.
Area of technical uncertainty for susceptibility testing of amoxicillin/clavulanate against Escherichia coli: analysis of automated system, Etest and disk diffusion methods compared to the broth microdilution reference
Authors: A. Soares, M. Pestel-Caron, F. Leysour de Rohello, G. Bourgoin, S. Boyer, F. Caron
Journal: Clinical Microbiology and Infection (2020)

ObjectivesThe European Committee on Antimicrobial Susceptibility Testing (EUCAST) recently warned about an area of technical uncertainty (ATU) of amoxicillin/clavulanate (AMX/C) disk susceptibility testing against members of the Enterobacterales. Thus, we aimed to compare the reliability of three routine methods and to evaluate the impact of the ATU.Methods286 Escherichia coli strains (including 159 AMX-resistant strains) were categorized for the two EUCAST AMX/C breakpoints by disk diffusion (Bio-Rad), the Phoenix automated system (Becton Dickinson) and the Etest (AES) compared to the broth microdilution reference method.ResultsBy microdilution, 84.2% of strains were AMX/C-susceptible using the urinary breakpoint (MIC ≤32 mg/L) and 62.2% using the systemic breakpoint (MIC ≤8 mg/L), with 63.6% of MICs between 4 and 16 mg/L. For the systemic breakpoint, category agreement (CA) and very major error (VME) were unacceptable for the Etest (71.7% and 27.3%), disk (73.1% and 23.4% at 19-mm cut-off) and to a lesser extent for the Phoenix system (83.6% and 10.5%). For disks, an unacceptable VME rate was observed for diameters up to 22 mm, probably due to overcharged disks. For the Etest, VMEs were high at 6 mg/L (46/63) and 8 mg/L (22/29). For the urinary breakpoint, CA was more acceptable for disk (88.9%) and Etest (84.3%) but was unevaluable for Phoenix.ConclusionAMX/C susceptibility testing of E. coli for systemic breakpoint was unreliable with the three routine methods, explained mainly by the high prevalence (~60%) of strains with microdilution MICs around the breakpoint (8 mg/L). Our data confirmed the EUCAST 19–20-mm ATU for disk and suggest introducing ATU for Etest MIC values of 6 and 8 mg/L.