tbuckley/cabot-search huggingface dataset:
Abstract P312: Abstract 14806: Association of Television Viewing With Incident Venous Thromboembolism: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Jordan Munger, Insu Koh, George Howard, Virginia Howard, Timothy Plante, Mary Cushman, Neil Zakai
Journal: Circulation (2019)

Introduction: Previous studies have linked TV watching with increased venous thromboembolism (VTE) risk independent of physical activity or other VTE risk factors. This finding warrants replication in a contemporary and geographically diverse cohort. Hypothesis: We hypothesized that TV watching is associated with increased hazard of VTE independent of physical activity and other VTE risk factors. Methods: From 2003-2007 REGARDS enrolled 30,239 participants aged 45+ years, who were surveyed for baseline TV viewing behavior and followed for VTE events. Daily TV viewing was categorized as &lt;2 hours, 2 to 4 hours, and 4+ hours. Physical activity was classified as high, medium or low based on weekly number of times participants reported activity sufficient to work up a sweat. Excluding those with prebaseline VTE, log-rank tests and Cox proportional hazards models were used to describe associations, adjusting for physical activity, age, sex, BMI, race, region, C-reactive protein (CRP) and estimated glomerular filtration rate (EGFR). In a sensitivity analysis, missing data were imputed by multiple imputation with chained equations. Results: TV viewing was not associated with increased VTE incidence by the log-rank test (p=0.33). In multivariable models shown in Table, greater TV watching did not increase VTE risk. In the complete case and imputation analyses, established VTE risk factors (older age, male sex, obesity, and CRP) were strongly associated with VTE. Depending on the model, high or medium physical activity was either significantly protective or trended towards protective against VTE (Table). Conclusions: In this contemporary cohort, in contrast to earlier studies, TV watching was not associated with VTE risk after accounting for confounders including obesity and physical activity. Traditional risk factors were associated with VTE risk suggesting this is not a cohort-specific issue. Findings could be due to differences in risk factor profiles in older and newer studies or differences in measurements of TV watching.
Alpha/Beta T Cell Depleted Haploidentical Transplantation Results in High Survival in Pediatric Patients with Acute Myeloid Leukemia
Authors: Larisa Shelikhova, Maria Ilushina, Zhanna Shekhovtsova, Elena Kurnikova, Galina Novichkova, Alexey A Maschan, Michael Maschan
Journal: Blood (2017)
Efficacy and Safety of Eltrombopag in Chinese Patients with Chronic Immune Thrombocytopenia: Stage 2 Results from a Multicenter Phase III Study
Authors: Renchi Yang, Liu Xiaofan, Junmin Li, Ming Hou, Jin Jie, Meijuan Huang, Ziqiang Yu, Xiaojun Xu, Xiaohui Zhang
Journal: Blood (2018)
Abstract 14134: Fractional Flow Reserve is Better Than Duplex Ultrasound and Angiography for Predicting the Clinical Significance of Peripheral Arterial Lesions
Authors: Mostafa A Albayati, Ashish Patel, Benjamin Hardy, Tommaso Donati, Sanjay Patel, Lukla Biasi, Hany Zayed, Leo Monzon, Narayanan Thulasidasan, Athanasios Diamantopoulos, Divaka Perera, Alberto Smith, Bijan Modarai
Journal: Circulation (2018)

Introduction: Peripheral arterial lesions are currently assessed by duplex ultrasound (DUS), computed tomography (CTA) and intra-arterial angiography (IA). We compared these assessments with fracti...
Abstract 17355: Multi-Modal Imaging Evaluation of the Aortic Root:ECG-gated and Non-ECG-Gated Computed Tomography versus Echocardiography
Authors: Elie Balesh, Paras Bhatt, Perry Choi, Hamid R Mojibian
Journal: Circulation (2012)

The main diagnostic imaging modalities currently used to image the aortic root and ascending aorta include transthoracic echocardiography (TTE) and either ECG-gated or non-ECG-gated computed tomography (CT), each with its respective advantages and disadvantages. This study aimed to examine the reproducibility and agreement of inter-reader measurements of the aortic root made on all three imaging modalities. The results of this study revealed that inter-cardiologist measurements of the aortic root performed on echocardiography lack reproducibility (mean difference of 2.9 ± 5.76 mm). Aortic root measurements made on ECG-gated CT studies more closely agree with measurements made on echocardiography than do those made on non-ECG-gated CT studies (mean differences of 0.4 ± 3.93 mm versus 0.9 ± 5.92 mm in the axial dimension and -0.2 ± 3.82 mm versus 1.1 ± 5.46 mm in the orthogonal dimension). When a single radiologist reviews a set of both ECG-gated and non-ECG-gated CTs, the mean difference of axial aortic ro...
Abstract P320: Validation of Smartphone-Recorded Physical Activity for Predicting Cardiorespiratory Fitness
Authors: Micah T Eades, Stephen P Juraschek, Ernest V Gervino, Kenneth J Mukamal
Journal: Circulation (2019)

Introduction: While most smartphones can track physical activity, whether this readily available data is associated with clinically meaningful outcomes is unknown. We tested the hypothesis that smartphone-recorded physical activity is associated with cardiorespiratory fitness as measured by peak metabolic equivalents of task (METs) achieved on an exercise stress test. Methods: We recruited 51 Apple iPhone users from the Beth Israel Deaconess Cardiovascular Stress Testing Laboratory between September 2017 - June 2018. We securely downloaded iPhone activity episodes, or epochs, and calculated cumulative steps, distance, and duration; peak speed and duration; and average daily peaks for specific intervals preceding stress tests. Age, gender, height, weight, and METs were obtained from the medical record. In a 70% training set, we used linear regression to determine relationships between individual components of physical activity and METs and to derive a multivariable prediction algorithm for METs. We then tested the best performing algorithm (based on Akaike Information Criterion) in a 30% test set. Results: We collected over 1.1 million activity epochs with a median of 17,103 epochs per participant. Twenty participants were female, median age [interquartile range] was 67 [53, 71] years, and median time preceding stress test [range] was 535 [13, 1,147] days. Average daily peak speed at 180 days most strongly correlated with METs (R 2 =0.44, p&lt;0.001), and correlation was similar at 3 days (R 2 =0.41, p&lt;0.001). The best-fitting multivariable model included age, gender, height, weight, and average peak speed at 180 days. Conclusion: Smartphone-recorded physical activity is readily available and strongly associated with cardiorespiratory fitness, even in an external validation set.
Targeting the ubiquitin ligase SKP2 in the myeloma stem-cell like side population.
Authors: Ehsan Malek, Mohamed Abdel Malek, James J Driscoll
Journal: Journal of Clinical Oncology (2015)

e13510 Background: While anti-myeloma therapies are effective in eradicating the bulk of tumor cells, intrinsically drug resistant, clonogenic tumor-initiating subpopulations contribute to disease relapse and poor outcomes in multiple myeloma (MM). Side population (SP) cells are an enriched source of therapy-resistant, tumor-initiating cells with stem cell-like features. Here, we investigated the molecular determinants responsible for chemoresistance in the myeloma SP to then identify actionable therapeutic targets. Methods: Side population (SP) cells were isolated from myeloma cell lines and patient samples using Hoechst 33342 dye-based flow cytometry. SP cells represented 1-2% of the tumor population and were used in cell-based assays to determine chemosensitivities relative to the non-SP cells. Results: Gene expression analysis indicated that components of the E3 ubiquitin ligase Skp1-Cul1-FboxSkp2 (SCFSkp2) complex were hyperexpressed in myeloma patients. SP cells were less sensitive to the anti-myeloma effects of the proteasome inhibitors (PIs) bortezomib, carfilzomib and ixazomib relative to non-SP cells. The relative percentage of SP cells was significantly greater in cultures of myeloma cells generated with acquired resistance to each PI. Genetic ablation of Skp2 or Cullin-1 synergistically enhanced the cytotoxic effect of bortezomib. A high-throughput assay was performed using large databases and chemical libraries to identify novel lead compounds that inhibited SCFSkp2-dependent ubiquitination activity. Bortezomib co-treatment with a lead compound identified here enhanced the anti-myeloma effect against SP cells isolated from cell lines and patient bone marrow samples. Conclusions: Taken together, we identify novel molecular determinants of chemoresistance in the myeloma stem cell-like SP. Functional assays demonstrated that SCFSkp2 is hyperexpressed in SP cells and represents an actionable drug target. Pharmacologics to selectively disrupt SCFSkp2 activity hold promise to selectively target chemoresistance with potential therapeutic benefit for myeloma patients.
Association of Midlife Diet With Subsequent Risk for Dementia
Authors: Tasnime N. Akbaraly, Archana Singh-Manoux, Aline Dugravot, Eric J. Brunner, Mika Kivimäki, Séverine Sabia
Journal: JAMA (2019)

<h3>Importance</h3> Observational studies suggest that diet is linked to cognitive health. However, the duration of follow-up in many studies is not sufficient to take into account the long preclinical phase of dementia, and the evidence from interventional studies is not conclusive. <h3>Objective</h3> To examine whether midlife diet is associated with subsequent risk for dementia. <h3>Design, Setting, and Participants</h3> Population-based cohort study established in 1985-1988 that had dietary intake assessed in 1991-1993, 1997-1999, and 2002-2004 and follow-up for incident dementia until March 31, 2017. <h3>Exposures</h3> Food frequency questionnaire to derive the Alternate Healthy Eating Index (AHEI), an 11-component diet quality score (score range, 0-110), with higher scores indicating a healthier diet. <h3>Main Outcome and Measures</h3> Incident dementia ascertained through linkage to electronic health records. <h3>Results</h3> Among 8225 participants without dementia in 1991-1993 (mean age, 50.2 years [SD, 6.1 years]; 5686 [69.1%] were men), a total of 344 cases of incident dementia were recorded during a median follow-up of 24.8 years (interquartile range, 24.2-25.1 years). No significant difference in the incidence rate for dementia was observed in tertiles of AHEI exposure during 1991-1993, 1997-1999 (median follow-up, 19.1 years), and 2002-2004 (median follow-up, 13.5 years). Compared with an incidence rate for dementia of 1.76 (95% CI, 1.47-2.12) per 1000 person-years in the worst tertile of AHEI (lowest tertile of diet quality) in 1991-1993, the absolute rate difference for the intermediate tertile was 0.03 (95% CI, −0.43 to 0.49) per 1000 person-years and for the best tertile was 0.04 (95% CI, −0.42 to 0.51) per 1000 person-years. Compared with the worst AHEI tertile in 1997-1999 (incidence rate for dementia, 2.06 [95% CI, 1.62 to 2.61] per 1000 person-years), the absolute rate difference for the intermediate AHEI tertile was 0.14 (95% CI, −0.58 to 0.86) per 1000 person-years and for the best AHEI tertile was 0.14 (95% CI, −0.58 to 0.85) per 1000 person-years. Compared with the worst AHEI tertile in 2002-2004 (incidence rate for dementia, 3.12 [95% CI, 2.49 to 3.92] per 1000 person-years), the absolute rate difference for the intermediate AHEI tertile was −0.61 (95% CI, −1.56 to 0.33) per 1000 person-years and for the best AHEI tertile was −0.73 (95% CI, −1.67 to 0.22) per 1000 person-years. In the multivariable analysis, the adjusted hazard ratios (HRs) for dementia per 1-SD (10-point) AHEI increment were not significant as assessed in 1991-1993 (adjusted HR, 0.97 [95% CI, 0.87 to 1.08]), in 1997-1999 (adjusted HR, 0.97 [95% CI, 0.83 to 1.12]), or in 2002-2004 (adjusted HR, 0.87 [95% CI, 0.75 to 1.00]). <h3>Conclusions and Relevance</h3> In this long-term prospective cohort study, diet quality assessed during midlife was not significantly associated with subsequent risk for dementia.
Abstract MP33: Modes of Physical Activity Engagement Differ by Federal Poverty Level Among Men and Women: The National Health and Nutrition Examination Survey (NHANES) 2007-2014
Authors: Layton Reesor, Rosenda Murillo, Ashley Dao, Daphne C Hernandez
Journal: Circulation (2019)

Introduction: Research has consistently identified the health benefits of physical activity (PA) and that low-income populations engage in less PA than their more affluent counterparts and may differ by gender. However, research has focused on leisure time PA (LTPA) with less emphasis on PA engagement from employment and transportation. This study aims to determine if those in lower Federal Poverty Level (FPL) categories differ in their modes of PA engagement compared to those of higher FPL categories. Hypothesis: We hypothesized that individuals of lower FPL status would be more likely to meet PA guidelines (≥150 minutes moderate to vigorous PA) from employment and transportation PA and less likely to meet PA guidelines from LTPA compared to those of higher FPL status. Methods: We used cross-sectional data from NHANES 2007-2014 participants aged 21 to 59 years (females: n =6,736; males: n=6,047). Weighted logistic regression models were used to estimate the association between FPL (FPL ≤0.99, 1.00-1.99, 2.00-2.99 vs FPL ≥ 3.00) and meeting PA guidelines in three domains: employment, transportation, and LTPA. Models were stratified by sex and adjusted for weight status, age, race, nativity, marital status, education, employment, and health insurance. Results: Among women, those of lower FPL had increased odds of meeting PA guidelines from employment [(FPL ≤ 0.99: OR: 1.53; 95% CI: 1.13, 2.06), (FPL 1.00-1.99: OR: 1.41; 95% CI: 1.07, 1.88). Those in the 2.00-2.99 FPL category had similar odds of meeting PA guidelines from employment (OR: 1.39; 95% CI: 0.99, 1.94), compared to those FPL ≥ 3.00. Women of lower FPL had similar odds of meeting PA guidelines from transportation compared to those FPL ≥ 3.00 ( p &gt; .05). Further, women of lower FPL were significantly less likely to meet PA recommendations from LTPA [(FPL ≤ 0.99: OR: 0.47; 95% CI: 0.39, 0.57), (FPL 1.00-1.99: OR: 0.51; 95% CI: 0.41, 0.62), (FPL 2.00-2.99: OR: 0.72; 95% CI: 0.58, 0.90)]. Among men, only those in the 2.00-2.99 category having increased odds of meeting PA guidelines from employment (OR: 1.49; 95% CI: 1.19, 1.86). Only the lowest FPL category men (FPL ≤0.99) had increased odds of meeting PA guidelines from transportation (OR: 1.80; 95% CI: 1.29, 2.51). Similar to women, lower FPL men were significantly less likely to meet PA recommendations from LTPA [(FPL ≤ 0.99: OR: 0.63; 95% CI: 0.51, 0.79), (FPL 1.00-1.99: OR: 0.58; 95% CI: 0.48, 0.70), (FPL 2.00-2.99: OR: 0.68; 95% CI: 0.55, 0.84)]. Conclusions: These findings suggest that modes of PA engagement differ by FPL category among men and women. Researchers studying PA among low-income populations must assess employment and transportation PA in addition to LTPA in order to accurately estimate PA engagement. Practitioners attempting to increase PA among low-income populations need to consider other modes of PA rather than solely focusing on LTPA.
EBF1-Mediated Upregulation of Ribosome Assembly Factor PNO1 Contributes to Cancer Progression by Negatively Regulating the p53 Signaling Pathway
Authors: Aling Shen, Youqin Chen, Liya Liu, Yue Huang, Hongwei Chen, Fei Qi, Jiumao Lin, Zhiqing Shen, Xiangyan Wu, Meizhu Wu, Qiongyu Li, Liman Qiu, Na Yu, Thomas J. Sferra, Jun Peng
Journal: Cancer Research (2019)

Abstract The RNA-binding protein PNO1 is critical for ribosome biogenesis, but its potential role in cancer remains unknown. In this study, online data mining, cDNA, and tissue microarrays indicated that PNO1 expression was higher in colorectal cancer tissue than in noncancerous tissue, and its overexpression was associated with worse patient survival. Gain-of-function and loss-of-function studies demonstrated that PNO1 knockdown suppressed growth of colorectal cancer cells in vitro and in vivo, while PNO1 overexpression promoted colorectal cancer cell proliferation in vitro. In colorectal cancer cells expressing wild-type p53, PNO1 knockdown enhanced expression of p53 and its downstream gene p21, and reduced cell viability; these effects were prevented by p53 knockout and attenuated by the p53 inhibitor PFT-α. Moreover, PNO1 knockdown in HCT116 cells decreased levels of 18S rRNA, of 40S and 60S ribosomal subunits, and of the 80S ribosome. It also reduced global protein synthesis, increasing nuclear stress and inhibiting MDM2-mediated ubiquitination and p53 degradation. Overexpressing EBF1 suppressed PNO1 promoter activity and decreased PNO1 mRNA and protein, inhibiting cell proliferation and inducing cell apoptosis through the p53/p21 pathway. In colorectal cancer tissues, the expression of EBF1 correlated inversely with PNO1. Data mining of online breast and lung cancer databases showed increased PNO1 expression and association with poor patient survival; PNO1 knockdown reduced cell viability of cultured breast and lung cancer cells. Taken together, these findings indicate that PNO1 is overexpressed in colorectal cancer and correlates with poor patient survival, and that PNO1 exerts oncogenic effects, at least, in part, by altering ribosome biogenesis. Significance: This study identifies the ribosome assembly factor PNO1 as a potential oncogene involved in tumor growth and progression of colorectal cancer.
Neither biological nor symptomatology reductionism: A call for integration in psychopathology research
Authors: Benjamin C. Nephew, Marcelo Febo, Hudson P Santos
Journal: Behavioral and Brain Sciences (2019)

Abstract We agree with Borsboom et al. in challenging neurobiological reductionism, and underscore some specific strengths of a network approach. However, they do not acknowledge that a similar problem is present in current psychosocial frameworks. We discuss this challenge as well as describe valuable parallels between symptom and neurobiological network theories that will substantially augment psychopathological research when integrated.
Olaparib combined with abiraterone in patients with metastatic prostate cancer: Safety run-in from a phase II study.
Authors: Noel W. Clarke, Robert Shepard, Stuart Spencer, Robert H. Jones
Journal: Journal of Clinical Oncology (2015)

e16026 Background: Olaparib (Lynparza), a PARP inhibitor with antitumor activity in germline (g) BRCA1/2 mutation-associated breast and ovarian cancer, has indicated antitumor activity in gBRCA1/2 mutation-associated prostate cancer (Kaufman et al. JCO 2014). Abiraterone is approved for patients with metastatic castration-resistant prostate cancer (mCRPC) before chemotherapy and after docetaxel-based chemotherapy. Reported here is an open-label safety run-in assessment (part A) from a randomized, placebo-controlled Phase II study (NCT01972217) of olaparib in combination with abiraterone. Methods: Patients (pts) with mCRPC in prior receipt of docetaxel-based chemotherapy were initially administered olaparib 200 mg twice daily (bid) and abiraterone 1000 mg once daily (qd). After 3 pts had received ≥ 14 days’ treatment with both olaparib and abiraterone, dose-limiting toxicities (DLTs) were assessed by a safety review committee (SRC). If ≤ 1 DLT was observed, either olaparib was escalated to 300 mg bid alone for 3–7 days then combined with abiraterone 1000 mg qd (group 1), or abiraterone 1000 mg qd was administered alone for 5–7 days then in combination with olaparib 300 mg bid (group 2). Prednisone or prednisolone 5 mg bid was administered with abiraterone throughout. Results: In total, 16 pts enrolled. In the 3 pts receiving olaparib 200 mg bid and abiraterone 1000 mg qd, no DLTs were observed. In the 13 pts (group 1, n = 7; group 2, n = 6) subsequently dosed with olaparib 300 mg bid and abiraterone 1000 mg qd, no DLTs were observed in 9 who completed > 2 weeks of treatment, 3 were still receiving treatment ( < 2 weeks) and 1 (group 1) withdrew consent following an adverse event (AE) of grade 1 nausea, which was not considered a DLT by the SRC. At the time of reporting 41 AEs had been observed in 10 pts, of which nausea occurred most frequently (5 pts), followed by vomiting and loose stools (3 pts each). No serious AEs considered related to olaparib were observed. Conclusions: DLTs were not observed in any pt dosed with olaparib 200 mg bid (n = 3) or 300 mg bid (n = 9). Olaparib 300 mg bid was considered an appropriate dose for further study in combination with abiraterone in pts with mCRPC. Clinical trial information: NCT01972217.
Diagnostic Methods Used to Classify Confirmed and Probable Cases of Spotted Fever Rickettsioses — United States, 2010–2015
Authors: Alison M. Binder, Kristen Nichols Heitman, Naomi A. Drexler
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Spotted fever rickettsioses (SFR), including Rocky Mountain spotted fever (RMSF), are nationally notifiable diseases in the United States caused by spotted fever group Rickettsia. The annual incidence of SFR increased from 1.7 cases per 1 million persons in 2000 to 13.2 in 2016 (1,2). Although this demonstrates a substantial increase in SFR cases, the actual magnitude of the increase is questionable because the current case definition allows for nonspecific laboratory criteria to support diagnosis (3). To analyze the quality of laboratory data used to support the diagnosis of SFR cases with illness onset during 2010-2015, CDC examined supplementary case report forms. Among 16,807 reported cases, only 167 (1.0%) met the confirmed case definition, and the remaining 16,640 (99.0%) met the probable case definition. The most common supportive laboratory evidence for probable cases was elevated immunoglobulin G (IgG) antibody titer by indirect immunofluorescence assay (IFA), which was reported for 14,784 (88.8%) probable cases. Antibodies to spotted fever group Rickettsia can persist for months or years following infection, making a single antibody titer unreliable for diagnosing incident disease without a convalescent specimen. Increased use of molecular assays and use of paired and appropriately timed IFA IgG testing practices could improve understanding of SFR epidemiology and increase the accuracy of disease incidence estimates.
Sonothrombolysis in ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention
Authors: Wilson Mathias, Jeane M. Tsutsui, Bruno G. Tavares, Agostina M. Fava, Miguel O.D. Aguiar, Bruno C. Borges, Mucio T. Oliveira, Alexandre Soeiro, Jose C. Nicolau, Henrique B. Ribeiro, Hsu Po Chiang, João C.N. Sbano, Abdulrahman Morad, Andrew Goldsweig, Carlos E. Rochitte, Bernardo B.C. Lopes, José A.F. Ramirez, Roberto Kalil Filho, Thomas R. Porter
Journal: Journal of the American College of Cardiology (2019)