tbuckley/cabot-search huggingface dataset:
Suppression of immune effector responses in ovarian cancer ascites
Authors: Seigo Kashimura, Masanori Terashima, Satoshi Otani, Mika Hoshino, Norio Kanzaki, Mitsukazu Gotoh
Journal: Cancer Research (2004)

676   Specific immunotherapy using dendritic cells (DC) could be be a promising therapy for advanced malignant diseases when adequate innate immunity is mounted on specific immunity . Toll-like receptor (TLR) is a key molecule to activate innate immunity. Meanwhile some kinds of TLR have been reported to be up-regulated by paclitaxel, one of anti-cancer agents in a murine model. In order to examine the effect of anticancer agents on activation of innate immunity in human DCs, we investigated the expression of TLR, IRAK-4 and NF-κB mRNA in DCs by docetaxel (TXT). Human peripheral blood mononuclear cells (PBMC) were collected from five healthy volunteers and cultured in serum free medium (AIM-V) in the presence of interleukin-4 and granulocyte macrophage stimulating factor for 5 days to derive immature DCs (iDCs). TXT at a concentration of 1x10-8M was added and cultured for 1, 2, 3 or 4 hr. After cultivation, cells were harvested and total RNA was extracted by AGPC method. Expressions of TLR-4, TLR-9, IRAK4 and NF-κB mRNA in iDC were examined using real-time RT-PCR. There was no significant change in TLR-9 mRNA level after TXT treatment. On the other hand TLR4 mRNA was up-regulated in iDCs peaked at 2 hr after TXT treatment. No significant changes in IRAK4 and NF-kappaB mRNA levels, which are downstream signals for activation of DCs, were obsereved throughout the experimental period. Up-regulation of TLR4 mRNA by TXT was observed in iDCs. However, the up-regulation of downstream signals for activation DCs was not demonstrated. The present study indicates that docetaxel can induce up-regulation of TLR4 of human iDC,although, the precise role of TLR4 on activation of DCs needs to beelucidated in the future experiment.
DRES-10. DRD5 IS A MODULATOR OF GLIOMA SUSCEPTIBILITY TO DRD2 ANTAGONISM BY ONC201
Authors: Varun Vijay Prabhu, Neel Madhukar, Coryandar Gilvary, C Leah B Kline, Rohinton Tarapore, Wafik El-Deiry, Faye Doherty, Alexander VanEngelenburg, Jessica Durrant, Cyril Benes, Wolfgang Oster, Olivier Elemento, Joshua Allen
Journal: Neuro-Oncology (2018)

ONC201 is the first selective antagonist of dopamine receptor D2 (DRD2) and D3 (DRD3) for clinical oncology that has exhibited preliminary clinical activity in high grade gliomas. We investigated DRD2 dysregulation in glioma and its role in ONC201 efficacy. Investigating CRISPR screens across a spectrum of cancer revealed that glioma cell lines had the highest DRD2 gene essentiality scores, indicating that glioma is a tumor type with the most vulnerability to DRD2 antagonism. Investigation of TCGA revealed that DRD2 is highly expressed in glioblastoma relative to other dopamine receptor family members and is associated with a relatively poor clinical prognosis. Tissue microarray analysis confirmed DRD2 overexpression in glioblastoma relative to normal brain. A linear correlation between DRD2 mRNA and ONC201 GI50 was observed among NCI60 glioblastoma cell lines. Similarly, we found a significant concordance between a cell line’s sensitivity to ONC201 within the Genomics of Drug Sensitivity in Cancer (GDSC) panel and its DRD2 gene essentiality score. Next, we ranked the relative contribution of each dopamine receptor to ONC201 efficacy using a bioinformatics approach based on a generalized linear model. We found that the strongest negative contributor was DRD2 – where a negative contribution denotes a decreased IC50 value as expression increases. Interestingly, DRD5, a D1-like dopamine receptor that counteracts DRD2 signaling, was measured as having the highest positive score – indicating that low expression of DRD5 was correlated with ONC201 efficacy. DRD5 expression was significantly inversely correlated with ONC201 potency in the NCI60 and GDSC datasets. Furthermore, a missense DRD5 mutation was identified in tumor cells with acquired resistance to ONC201. Resistance could be recapitulated with overexpression of the mutant or wild-type DRD5 gene. In conclusion, DRD2 dysregulation and DRD5 expression predict preclinical ONC201 glioma sensitivity that may be used to identify additional settings for clinical evaluation.
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines
Authors: Scott M. Grundy, Neil J. Stone, Alison L. Bailey, Craig Beam, Kim K. Birtcher, Roger S. Blumenthal, Lynne T. Braun, Sarah de Ferranti, Joseph Faiella-Tommasino, Daniel E. Forman, Ronald Goldberg, Paul A. Heidenreich, Mark A. Hlatky, Daniel W. Jones, Donald Lloyd-Jones, Nuria Lopez-Pajares, Chiadi E. Ndumele, Carl E. Orringer, Carmen A. Peralta, Joseph J. Saseen, Sidney C. Smith, Laurence Sperling, Salim S. Virani, Joseph Yeboah
Journal: Circulation (2019)
Abstract 13168: Food Quality Score and the Risk of Coronary Heart Disease
Authors: Teresa Fung, An Pan, Tao Hou, Dariush Mozzafarian, Shilpa Bhupathiraju, Walter Willett, Frank Hu
Journal: Circulation (2015)

Introduction: We have previously derived a food based diet quality score associated with weight change. In this analysis, we prospectively assessed the association between this score and risk of coronary heart disease (CHD). Methods: We followed 74,667 women in the Nurse’ Health Study (baseline age 35-55 y), 28,977 men in the Health Professionals Follow-up Study (baseline age 50-72), and 92,513 women in the Nurses’ Health Study 2 (baseline age 25-42) without a history of cardiovascular disease for up to 26 years between 1984 and 2011. Diet was assessed up to 7 times using repeated food frequency questionnaires. We computed the Food Quality Score (FQS) for each individual. A higher FQS score represents a healthier diet. The association between the FQS and CHD risk was assessed using Cox proportional hazard model controlling for potential confounders. We also compared the strength of association of FQS with other diet quality scores. Results: We ascertained 6497 incident CHD events, including 4594 nonfatal myocardial infarct (MI) and 2055 fatal cases. Comparing top to bottom deciles, the pooled RR was 0.66 (95% CI=0.58-0.74, p trend&lt;0.001) for total CHD, 0.63 (0.54-0.73, p trend&lt;0.001) for non-fatal MI, and 0.73 (0.59-0.90, p trend=0.001) for fatal MI. The association for CHD was significant in lean (BMI&lt;25) and overweight (BMI&gt;=25) individuals, those with or without a family history of MI, and physical activity above or below the median. When comparing the FQS with other diet quality scores that have previously been associated to lower CHD risk, one standard deviation increase in the FQS was not significantly different from the Alternate Mediterranean Diet score, the Alternate Healthy Eating Index-2010 or the Dietary Approaches to Stop Hypertension score in its association with CHD risk. Conclusion: A higher FQS was associated with lower CHD risk. The FQS was comparable to food and nutrient based diet quality score that have previously been associated with lower CVD risk and indicates a potential to develop a simple food only diet quality for public health applications of assessing diet quality.
RARE-31. NATURAL HISTORY OF T-CELL CNS LYMPHOMA
Authors: Akhilesh Padhye, Ekokobe Fonkem, Wencong Chen
Journal: Neuro-Oncology (2018)

Intravascular T-Cell Lymphoma is a rare form of non-Hodgkin’s lymphoma. The clinical manifestations, treatment, and outcomes are poorly characterized. PURPOSE: This article provides a comprehensive analysis of intravascular T-Cell lymphoma from 1986–2018 to better understand this disease. METHODS/ANALYSIS: Studies from PubMed, Cochrane Review, and Springer were selected if patients demonstrated histologically or biopsy proven disease. Information on demographics, histology, site of disease, imaging, EBV exposure, and treatments was compiled. Univariate Cox proportional hazards model was used to analyze impact of these single variables and survival. Overall survival KM estimate was plotted. 56 unique patients (median age: 59, range: 0–87) were identified. Males were more affected (58.9%), with the most common primary disease manifestation being the skin (51.7%). Patients who were alive during time of study publication were in the minority (30.4%). Median time to diagnosis was 2.1 (range 0–18) months, with median time from first treatment to death at 3.1 (0–10) months. The hazard odds ratio for primary site skin involvement versus other sites was 2.198 (p=0.0271). The remaining independent variables, including treatment therapies, were not shown to be statistically significant. Survival KM estimate showed a survival function of 0.22 at 20 months. Intravascular T-Cell Lymphoma is a devastating disease, characterized by rapid onset and low survival rates. With the exception of initial site of presentation, no other variables or therapies have shown to improve prognosis and outcomes. It is imperative to continue to study this rare disease to mitigate its devastating effects.
Abstract P258: Racial Disparity in 90-Day Post-Stroke Readmission - An MUSC Perspective
Authors: Pratik Y Chhatbar, Jihad S Obeid, Yujing Zhao, Daniel T Lackland, Robert J Adams
Journal: Circulation (2017)

Background: Readmissions after acute hospitalizations are a cause of both risk and expense, and many of them are potentially preventable. Importantly, risk-standardized hospital readmission rates are sometimes used as a yardstick of the quality of care offered. However, racial variability in readmissions might involve factors beyond quality of care and has not been studied extensively. Objective: To identify differences in readmissions between African Americans and other races and determine preventable readmissions from a pragmatic viewpoint. Methods: We obtained deidentified data from Medical University of South Carolina (MUSC) Electronic Data Warehouse (EDW) on adult admissions with index diagnosis considered as an ischemic stroke (or closely related) using International Classification of Diseases, Ninth Revision (ICD-9) codes 433.x, 434.x, 436.x, 437.x between January 2011 and June 2014. Of these, we determined readmission and reason for readmission over 90-day period. Readmission can be hospital or emergency room readmission. We obtained race as the only linked demographic. Results: Of the 1953 patients admitted with index diagnoses of stroke, 765 (39%), 1148 (59%) and 50 (1%) were African Americans, Caucasians and others, respectively. At 90-days, 256 patients were readmitted as in-patient, of which 128 (50%), 126 (49%) and 2 (1%) were African Americans, Caucasians and others, respectively. On the other hand, 241 patients visited Emergency Room, of which 175 (73%), 65 (26%) and 1 (1%) were African Americans, Caucasians and others, respectively. On adjusting readmissions to index admissions, 17%, 11% and 4% of African Americans, Caucasians and others, respectively, were readmitted in hospital, while 23%, 6% and 2% of African Americans, Caucasians and others, respectively, visited Emergency Room over 90-days period. Conclusions: 90-days readmission rates involve African Americans in a disproportionate manner. This demands further investigation on the etiology of readmission and the care offered.
NIMG-08. REPRODUCIBILITY OF HYPERPOLARIZED C-13 METABOLIC IMAGING IN PATIENTS WITH GLIOMA
Authors: Adam Autry, Jeremy Gordon, Marisa Lafontaine, Javier Villanueva-Meyer, Daniel Vigneron, Susan Chang, Sarah Nelson, Yan Li
Journal: Neuro-Oncology (2018)

As a non-invasive method for probing in vivo metabolism, hyperpolarized carbon-13 metabolic imaging may enhance the diagnostic assessment of response-to-treatment in patients with glioma. Having demonstrated the feasibility of applying this technique to human glioma (Park et al. 2017), the current study seeks to evaluate the reproducibility of carbon data by measuring serial metabolic changes in white matter. In total, 4 radiologically stable patients (2 male, 2 female) who were treated with radiation and TMZ for heterogeneous diagnoses (GBM, grade III oligo, gliosarcoma, secondary GBM) received either 2 (n=1) or 3 (n=3) serial exams. Following injection of hyperpolarized [1-13C]pyruvate, dynamic echo-planar imaging was acquired with a 3s temporal resolution and 2–8 cm3 spatial resolution. Dynamic data were summed together and the ratio of metabolically-produced lactate relative to pyruvate substrate (lac/pyr) was evaluated in segmented normal-appearing white matter (NAWM, >50% voxel). Median and SD of lac/pyr values in NAWM are reported for serial scans, along with %change per interval: P1-male [0.32 ± 0.14, 0.28 ± 0.11 (-12.5%), 0.33 ± 0.10 (+17.9%)]; P2-male [0.32 ± 0.10, 0.28 ± 0.10 (-12.5%)]; P3-female [0.37 ± 0.09, 0.45 ± 0.14 (+21.6%), 0.59 ± 0.19 (+31.1%)]; and P4-female [0.49 ± 0.14, 0.43 ± 0.12 (-12.2%), 0.44 ± 0.10 (2.3%)]. These results show an average absolute change of 15.7% in lac/pyr within NAWM over the entire population, with considerable overlap of the variance. Patient P3, who was treated with adjuvant agent pembrolizumab, also notably showed a serial increase in lac/pyr. When separating the population according to gender, females demonstrated a higher average lac/pyr value of 0.46, compared to 0.31 in males. In summary, our initial experience with serial hyperpolarized carbon data indicates that the range of lactate-to-pyruvate ratios is relatively consistent across patient scans, but may differ according to gender and adjuvant treatment. Future studies will evaluate changes in the T2 lesion relative to NAWM over the course of treatment.
Abstract P263: Acid-Base Status as a Modifier of Loss of Lean Mass During Intentional Weight Loss in Older Adults
Authors: Snezana Petrovic, Iris Leng, Michael P Walkup, Walter T Ambrosius, W. J Rejeski, Barbara J Nicklas
Journal: Circulation (2018)

Weight loss interventions present a unique challenge in older adults: relative loss of lean mass during weight loss, if superimposed on age-related sarcopenia may increase the risk for mobility disability. Relative loss of lean mass (25-30%) during weight loss depends on the severity/duration of caloric restriction, initial body mass, and concomitant exercise training. We hypothesized that subclinical imbalances of acid-base status (reflected in lower serum bicarbonate) may also affect relative loss of lean mass during weight loss. The rationale: even subtle imbalances of acid-base status (e.g. bicarbonate &lt;23 mmol) impact clinical outcomes in older adults such as gait speed or incidence of functional limitation, while bicarbonate supplementation reduces urinary nitrogen wasting and may improve physical function. However, data on acid-base balance and serum bicarbonate during moderate caloric restriction are lacking. We, therefore, analyzed 2 randomized, controlled weight loss trials (including moderate caloric restriction and exercise): The Diet, Exercise, and Metabolism for Older Women [DEMO; (58±5.2 y)] and Cooperative Lifestyle Program; [CLIP; (67±4.7 y)]. Serum bicarbonate was assessed as total CO 2 (in mmol) and whole body lean mass measured by dual-energy X-ray absorptiometry. The analysis showed that 48% of participants had bicarbonate &lt;23. DEMO participants with lower serum bicarbonate at baseline lost more lean mass during the intervention (unadjusted β(SE)=0.32(0.16); p=0.04; n=92). Adjustments for age, BMI, eGFR, % weight loss, baseline, intervention group, had little effect, but adjusting for protein intake during weight loss attenuated the association (β(SE)=0.17(0.15); p=0.28.). Similarly, a change in serum bicarbonate during the trial was associated with % lean mass change, but attenuated after controlling for protein intake. This is not unexpected: protein is acid-producing and one of two major determinants of net dietary acid load; higher dietary acid load correlates with lower serum bicarbonate, in older adults. Results from the CLIP trial were remarkably similar, and consistently, baseline serum bicarbonate level was marginally predictive of baseline daily protein intake, with highest baseline serum bicarbonate having the lowest protein intake [bicarbonate: &gt;24 (n=58); &gt;21-24 (n=121); &lt;21 (N=93); protein in g/kg body weight 0.7(0.4); 0.9(0.4); 0.8(0.4) respectively, p=0.057). In conclusion, our analysis suggests that higher serum bicarbonate before and during weight loss may ameliorate loss of lean mass, however, to obtain definitive answer such analysis needs to be conducted under conditions of controlled or randomized protein intake. Importantly, our findings suggest that oral bicarbonate supplementation, a simple and relatively safe intervention, may ameliorate loss of lean mass during weight loss interventions in older adults.
Financial Costs Incurred by Living Kidney Donors: A Prospective Cohort Study
Authors: Sebastian Przech, Amit X. Garg, Jennifer B. Arnold, Lianne Barnieh, Meaghan S. Cuerden, Christine Dipchand, Liane Feldman, John S. Gill, Martin Karpinski, Greg Knoll, Charmaine Lok, Matthew Miller, Mauricio Monroy, Chris Nguan, G.V. Ramesh Prasad, Sisira Sarma, Jessica M. Sontrop, Leroy Storsley, Scott Klarenbach
Journal: Journal of the American Society of Nephrology (2018)

Background Approximately 40% of the kidneys for transplant worldwide come from living donors. Despite advantages of living donor transplants, rates have stagnated in recent years. One possible barrier may be costs related to the transplant process that potential willing donors may incur for travel, parking, accommodation, and lost productivity. Methods To better understand and quantify the financial costs incurred by living kidney donors, we conducted a prospective cohort study, recruiting 912 living kidney donors from 12 transplant centers across Canada between 2009 and 2014; 821 of them completed all or a portion of the costing survey. We report microcosted total, out-of-pocket, and lost productivity costs (in 2016 Canadian dollars) for living kidney donors from donor evaluation start to 3 months after donation. We examined costs according to ( 1 ) the donor’s relationship with their recipient, including spousal (donation to a partner), emotionally related nonspousal (friend, step-parent, in law), or genetically related; and ( 2 ) donation type (directed, paired kidney, or nondirected). Results Living kidney donors incurred a median (75th percentile) of $1254 ($2589) in out-of-pocket costs and $0 ($1908) in lost productivity costs. On average, total costs were $2226 higher in spousal compared with emotionally related nonspousal donors ( P =0.02) and $1664 higher in directed donors compared with nondirected donors ( P &lt;0.001). Total costs (out-of-pocket and lost productivity) exceeded $5500 for 205 (25%) donors. Conclusions Our results can be used to inform strategies to minimize the financial burden of living donation, which may help improve the donation experience and increase the number of living donor kidney transplants.
Abstract 15738: PGC1alpha Regulates Decreased Mitochondrial Respiration in Aneurysmal Aortas of Fibulin-4 Mutant Mice
Authors: Ingrid van der Pluijm, P van Heijningen, J Burger, A IJpma, J.N van Vliet, K Schoonderwoerd, W Sluiter, L.J. Ringuette, D.H.W Dekkers, I Que, E.L. Kaijzel, L te Riet, C. Milanese, E MacFarlane, Devashish Das, R van der Linden, M. Vermeij, J. Demmers, P.G. Mastroberardino, E.C. Davis, H Yanagisawa, H Dietz, R Kanaar, J. Essers
Journal: Circulation (2017)

Thoracic aortic aneurysms are life-threatening and often diagnosed too late, underscoring the need to identify the underlying molecular sequence of events. We therefore examined the molecular mecha...
Endovascular Fenestration/Stenting First Followed by Delayed Open Aortic Repair for Acute Type A Aortic Dissection With Malperfusion Syndrome
Authors: Bo Yang, Carlo Maria Rosati, Elizabeth L. Norton, Karen M. Kim, Minhaj S. Khaja, Narasimham Dasika, Xiaoting Wu, Whitney E. Hornsby, Himanshu J. Patel, G. Michael Deeb, David M. Williams
Journal: Circulation (2018)

Background: Immediate open repair of acute type A aortic dissection is traditionally recommended to prevent death from aortic rupture. However, organ failure because of malperfusion syndrome (MPS) might be the most imminent life-threatening problem for a subset of patients. Methods: From 1996 to 2017, among 597 patients with acute type A aortic dissection, 135 patients with MPS were treated with upfront endovascular reperfusion (fenestration/stenting) followed by delayed open repair (OR). We compared outcomes between the first and second decades and observed mortalities with those expected with an “upfront OR for every patient” approach, determined using prognostic models from the literature (Verona, Leipzig-Halifax, Stockholm, Penn, and GERAADA [German Registry for Acute Aortic Dissection Type A] models). Results: Overall, in-hospital mortality improved between the 2 decades (21.0% versus 10.7%, P &lt;0.001). In the second decade, for patients with MPS initially treated with fenestration/stenting, mortality from aortic rupture decreased from 16% to 4% ( P =0.05), the risk of dying from organ failure was 6.6 times higher than dying from aortic rupture (hazard ratio=6.63; 95% CI, 1.5–29; P =0.01), and 30-day mortality after OR for MPS patients was 3.7%. Compared to the expected mortalities with the upfront OR for every patient models, our observed 30-day and in-hospital mortalities (9% and 11%, respectively) of all patients with acute type A aortic dissection were significantly lower ( P ≤0.03). Conclusions: Immediate OR is the strategy to prevent death from aortic rupture for the majority of patients with acute type A aortic dissection. However, relatively stable (no rupture, no tamponade) patients with MPS benefit from a staged approach: upfront endovascular reperfusion followed by aortic OR at resolution of organ failure.
Abstract 15035: Leadless Pacemakers for Syncope Associated With Bradycardia: A Retrospective Analysis of 954 Patients
Authors: Dipayon Roy, Annahita Sarcon, Melissa Ramos, Mary Huntsinger, Philip Chang, Rahul N Doshi
Journal: Circulation (2018)

Background: Traditional treatment for syncope secondary to bradycardia occasionally requires implantation of traditional transvenous pacemakers (TVP). However, traditional TVP are associated with c...