tbuckley/cabot-search huggingface dataset:
Abstract 17547: Stress Induced Chest Pain is Associated With a Better Survival in Patients With Suspected Coronary Artery Disease
Authors: Padmini Varadarajan, Ramdas G Pai
Journal: Circulation (2010)

Background and hypothesis: We hypothesized that exercise stress induced chest pain may be protective in patients with suspected coronary artery disease (CAD) by limiting levels of stress and amount of ischemia and also attracting attention to the possibility of CAD resulting in appropriate disease modifying therapy. This was tested in a large cohort of patients undergoing exercise stress testing. Methods: A total 9941 unique patients underwent exercise stress testing at our institution in the period 1993 to 2007 of whom 1494 (15%) had stress induced chest pain. Mortality data was obtained from National Death Index and survival was analyzed as a function of chest pain. Results: The patient characteristics were as follows: age 60±13 years, 68% men, baseline heart rate 75±14 bpm, mean blood pressure 130/79 mmHg, LV ejection fraction 56±15%. The peak stress heart rate was 132±24 bpm, and MET level obtained 8.5±3.5. Over 8.2 years there were 1885 deaths. Presence of chest pain on exercise was associated with b...
Severe asthma: Entering an era of new concepts and emerging therapies: Highlights of the 4th international severe asthma forum, Madrid, 2018
Authors: Sven F. Seys, Santiago Quirce, Ioana Agache, Cezmi A. Akdis, Montserrat Alvaro‐Lozano, Dario Antolín‐Amérigo, Leif Bjermer, Irina Bobolea, Matteo Bonini, Apostolos Bossios, Paul Brinkman, Andy Bush, Moises Calderon, Walter Canonica, Psacal Chanez, Mariana Couto, Ignacio Davila, Stefano Del Giacco, Victoria Del Pozo, Jonas S. Erjefält, Philippe Gevaert, Paul Hagedoorn, Liam G. Heaney, Enrico Heffler, Peter W. Hellings, Marek Jutel, Omer Kalayci, Marcin Maciej Kurowski, Stelios Loukides, Parameswaran Nair, Oscar Palomares, Eva Polverino, Silvia Sanchez‐Garcia, Joaquin Sastre, Jürgen Schwarze, Antonio Spanevello, Charlotte S. Ulrik, Omar Usmani, Maarten Van den Berge, Martina Vasakova, Susanne Vijverberg, Zuzana Diamant
Journal: Allergy (2019)
Abstract 20536: Cardiomyocyte Derived D-dopachrome Tautomerase Protects Against Heart Failure
Authors: Yina Ma, Kevin N Su, Jiasheng Zhang, Daniel Pfau, Xiaohong Wu, Xiaoyue Hu, Richard Bucala, Lawrence Young
Journal: Circulation (2016)

Left ventricular hypertrophy (LVH) is common in cardiovascular disease and predisposes to heart failure, however, the molecular mechanisms modulating the transition of LVH to heart failure remain i...
Abstract 13760: Symptom Onset to Door Time and Door to Balloon Time: Can We Further Decrease Mortality Post STEMI?
Authors: Razvan T Dadu, Lisa Kaltenbach, Mostafa El-Refai, Mahboob Alam, Daniel Wojdyla, Matthew Roe, Nasser Lakkis
Journal: Circulation (2017)

Introduction: National door to balloon time (DTBT) in STEMI continues to decrease with inconsistent reduction in mortality. Symptom onset to door time (SOTDT) may contribute to this discrepancy. Hy...
IMMU-11. RESPONSE OF T-CELLS UNDER THE INFLUENCE OF ADAMANTINOMATOUS CRANIOPHARYNGIOMA CYST FLUID
Authors: Trinka Vijmasi, Eric Prince, Ros Whelan, Andrea Griesinger, Andrew Donson, Susan Staulcup, Lindsay Hoffman, Nicholas Foreman, Michael Handler, Todd Hankinson
Journal: Neuro-Oncology (2019)

INTRODUCTION: Pediatric Adamantinomatous Craniopharyngioma (ACP) is well known for its association with poor quality of life in young patients. Biologically guided therapies are currently unavailable. We and others have shown that the ACP tumor microenvironment is infiltrated with immune cells and that ACP cyst fluid (CF) is enriched with cytokines. To identify potential targeted therapies, we seek to understand the response of normal human T-lymphocytes to ACP cyst fluid. METHODS: Cyst fluid was collected intraoperatively from pediatric ACP patients. Human T- cells enriched from PBMC fractions of healthy donors were activated by CD3/CD28/CD2 co-stimulation and cultured in IL-2 supplemented conditioned media containing either ACP CF at 10% or no cyst fluid for 24 hours, after which cells were placed in fresh media. After 48 hours, the supernatants were collected for IL-6 ELISA and the cells were immunolabelled for flow cytometry. RESULTS: CF treated T-cells demonstrated decreased IL-6 secretion compared to control media treated T-cells (124.8±10.9 pg/mL vs 231.25±30.6 pg/mL; P=0.04). The proportion of Helper T-cells double positive for CD25 and CD137 (CD4+CD25+CD137+) was decreased with CF treatment (61.0% ± 3.6 vs 72.5%± 0.2; P=0.04). The proportion of Cytotoxic T-cells double positive for CD25 and CD137 (CD8+CD25+CD137+) was also decreased with CF treatment (21.0% ± 0.1 vs 36.3% ± 1.1; P=0.003). CONCLUSION: This study characterizes the response of T-cells under the influence of ACP cyst fluid. The cytokine milieu of ACP cyst fluid appears to have immunomodulatory effects on activated T-cells. The decrease in IL-6 secretion and markers of T-cell activation may indicate an immunosuppressive environment, thus supporting the paradigm for compromised tumor immunosurveillance in pediatric ACP. Further studies to characterize immune cells and their extensive cytokine secretory profile in response to ACP cyst fluid, in order to more completely understand ACP immunopathology, are underway.
Abstract 18956: Comparison of Global and Regional Myocardial Strains in Patients With Heart Failure With a Preserved Ejection Fraction vs Hypertension vs Age Matched Control
Authors: Hyung Yoon Kim, Sung-Ji Park, Sang-Chol Lee, Shin Yi Jang, Myung Jin Park, Eun-Kyoung Kim, Sung-A Chang, Jin-Oh Choi, Seung Woo Park, Sung-Mok Kim, Yeon Hyeon Choe, Jae K. Oh
Journal: Circulation (2016)

Introduction, Hypothesis: The objective of this study was to analyze global and regional left ventricular (LV) strains using echocardiography speckle tracking in patients with HFpEF and compared those parameters with that of patients with hypertension and normal subjects. Methods: Each regional and global longitudinal, circumferential and radial strains were evaluated with echocardiography using speckle-tracking for fifty patients with HFpEF, fifty-six patients with hypertension and forty-six age-matched normal subjects. Diastolic strain rate was also determined. Results: Peak longitudinal, circumferential and radial strains and strain rate were globally reduced in patients with HFpEF compared to both hypertension patients and normal controls. In addition, the HFpEF patients demonstrated significantly lower longitudinal, circumferential and radial regional strain compared to both hypertension patients and normal controls, in all segments except in inferoseptal and inferolateral apical segments. Notably, g...
US officials charge 31 doctors over opioid prescribing
Authors: Owen Dyer
Journal: BMJ (2019)

US authorities have charged dozens of medical professionals in seven states with illegally prescribing more than 32 million opioid pills, in the largest operation yet against doctors profiting from the US opioid epidemic.

The 60 people indicted include 31 doctors, eight nurse practitioners, seven other licensed medical professionals, and seven pharmacists in Alabama, Kentucky, Louisiana, Ohio, Pennsylvania, Tennessee, and West Virginia. Most of the other people charged are physicians’ office managers and other clinic staff.

The indictments are the work of the new Appalachian Region Opioid Strike Force and come only four months after the group began its work in the region. It includes prosecutors, data analysts who search …
Opioids for chronic pain: US doctors are misapplying guideline, say its authors
Authors: Owen Dyer
Journal: BMJ (2019)

Government guidance for prescribing opioids that has informed most treatment for chronic pain in the US since 20161 is being interpreted in ways that can worsen the harms of addiction and leave patients suffering needless pain, its authors have said.

“Unfortunately, some policies and practices purportedly derived from the guideline have in fact been inconsistent with, and often go beyond, its recommendations,” wrote Deborah Dowell, Tamara Haegerich, and Roger Chou in the New England Journal of Medicine .2

They pointed to common mistakes in interpretation of the Centres for Disease Control and Prevention guidance, which have been identified by a recent consensus panel. …
Recognizing basal cell carcinoma on smartphone‐captured digital histopathology images with a deep neural network
Authors: Y.Q. Jiang, J.H. Xiong, H.Y. Li, X.H. Yang, W.T. Yu, M. Gao, X. Zhao, Y.P. Ma, W. Zhang, Y.F. Guan, H. Gu, J.F. Sun
Journal: British Journal of Dermatology (2019)

Pioneering effort has been made to facilitate the recognition of pathology in malignancies based on whole‐slide images (WSIs) through deep learning approaches. It remains unclear whether we can accurately detect and locate basal cell carcinoma (BCC) using smartphone‐captured images. To develop deep neural network frameworks for accurate BCC recognition and segmentation based on smartphone‐captured microscopic ocular images (MOIs). We collected a total of 8046 MOIs, 6610 of which had binary classification labels and the other 1436 had pixelwise annotations. Meanwhile, 128 WSIs were collected for comparison. Two deep learning frameworks were created. The ‘cascade’ framework had a classification model for identifying hard cases (images with low prediction confidence) and a segmentation model for further in‐depth analysis of the hard cases. The ‘segmentation’ framework directly segmented and classified all images. Sensitivity, specificity and area under the curve (AUC) were used to evaluate the overall performance of BCC recognition. The MOI‐ and WSI‐based models achieved comparable AUCs around 0·95. The ‘cascade’ framework achieved 0·93 sensitivity and 0·91 specificity. The ‘segmentation’ framework was more accurate but required more computational resources, achieving 0·97 sensitivity, 0·94 specificity and 0·987 AUC. The runtime of the ‘segmentation’ framework was 15·3 ± 3·9 s per image, whereas the ‘cascade’ framework took 4·1 ± 1·4 s. Additionally, the ‘segmentation’ framework achieved 0·863 mean intersection over union. Based on the accessible MOIs via smartphone photography, we developed two deep learning frameworks for recognizing BCC pathology with high sensitivity and specificity. This work opens a new avenue for automatic BCC diagnosis in different clinical scenarios. What's already known about this topic? The diagnosis of basal cell carcinoma (BCC) is labour intensive due to the large number of images to be examined, especially when consecutive slide reading is needed in Mohs surgery. Deep learning approaches have demonstrated promising results on pathological image‐related diagnostic tasks. Previous studies have focused on whole‐slide images (WSIs) and leveraged classification on image patches for detecting and localizing breast cancer metastases. What does this study add? Instead of WSIs, microscopic ocular images (MOIs) photographed from microscope eyepieces using smartphone cameras were used to develop neural network models for recognizing BCC automatically. The MOI‐ and WSI‐based models achieved comparable areas under the curve around 0·95. Two deep learning frameworks for recognizing BCC pathology were developed with high sensitivity and specificity. Recognizing BCC through a smartphone could be considered a future clinical choice.
Abstract 19765: Barriers to Implementation of a Health Promotion Program in Harlem, New York: The FAMILIA Study, an AHA Strategically Focused Research Network Study
Authors: Sameer Bansilal, Rajesh Vedanthan, Risa Jaslow, Martha Hadley, Amy Siskind, Carmina Marcial, Ana V Soto, Claire Kofler, Zahi A Fayad, Valentin Fuster
Journal: Circulation (2015)

Objective: The Harlem area of New York City has among the highest obesity and diabetes prevalence rates in the city. Nearly half of the children in the Head Start program and about 94% of adults are overweight or obese. We sought to identify factors that may impact the implementation of an integrated family-based health promotion program for children aged 3-5 years and their caregivers in Harlem. Methods: We conducted a qualitative study consisting of 5 focus group discussions (FGD) at two Head Start preschool centers in Harlem, NY. The FGDs included the following participants: parents, teachers, directors, educational directors, nutritionists, cooks, health, mental health and social service professionals. Content analysis of the transcript and notes was performed to identify salient themes. Relationships between and among themes were formulated. Findings: Twenty-five individuals participated in the FGDs. Seven themes emerged as potential barriers to program implementation. Program implications and specific strategies to address them were generated (Table). Conclusions: Formative work prior to program implementation has revealed important, actionable issues that will be addressed during the intervention period. This type of approach may be useful for other health promotion programs in similar settings.
Targeting Filamin A Reduces Macrophage Activity and Atherosclerosis
Authors: Sashidar Bandaru, Chandu Ala, Reza Salimi, Murali K. Akula, Matias Ekstrand, Sravani Devarakonda, Joakim Karlsson, Jimmy Van den Eynden, Göran Bergström, Erik Larsson, Max Levin, Jan Borén, Martin O. Bergo, Levent M. Akyürek
Journal: Circulation (2019)

The actin-binding protein FLNA (filamin A) regulates signal transduction important for cell locomotion, but the role of macrophage-specific FLNA during atherogenesis has not been explored.We analyzed FLNA expression in human carotid atherosclerotic plaques by immunofluorescence. We also produced mice with Flna-deficient macrophages by breeding conditional Flna-knockout mice ( Flna o/fl) with mice expressing Cre from the macrophage-specific lysosome M promoter ( LC). Atherosclerosis in vivo was studied by transplanting bone marrow from male Flna o/fl/ LC mice to atherogenic low-density lipoprotein receptor-deficient ( Ldlr-/-) mice; and by infecting Flna o/fl and Flna o/fl/ LC mice with AdPCSK9 (adenoviral vector overexpressing proprotein convertase subtilisin/kexin type 9). Furthermore, C57BL/6 mice were infected with AdPCSK9 and then treated with the calpain inhibitor calpeptin to inhibit FLNA cleavage.We found that macrophage FLNA expression was higher in advanced than in intermediate human atherosclerotic plaques. Flna o/fl/ LC macrophages proliferated and migrated less than controls; expressed lower levels of phosphorylated AKT and ERK1/2; exhibited reduced foam cell formation and lipid uptake; and excreted more lipids. The deficiency of Flna in macrophages markedly reduced the size of aortic atherosclerotic plaques in both Ldlr-/-BMT: Flnao/fl/LC and AdPCSK9-infected Flna o/fl/ LC mice. Intima/media ratios and numbers of CD68-positive macrophages in atherosclerotic plaques were lower in Flna-deficient mice than in control mice. Moreover, we found that STAT3 interacts with a calpain-cleaved carboxyl-terminal fragment of FLNA. Inhibiting calpain-mediated FLNA cleavage with calpeptin in macrophages reduced nuclear levels of phosphorylated STAT3, interleukin 6 secretion, foam cell formation, and lipid uptake. Finally, calpeptin treatment reduced the size of atherosclerotic plaques in C57BL/6 mice infected with AdPCSK9.Genetic inactivation of Flna and chemical inhibition of calpain-dependent cleavage of FLNA impaired macrophage signaling and function, and reduced atherosclerosis in mice, suggesting that drugs targeting FLNA may be useful in the treatment of atherosclerosis.
DIPG-31. FEASIBILITY OF HYPERPOLARIZED 13C METABOLIC IMAGING IN PEDIATRIC PATIENTS WITH DIPG AND OTHER CNS CANCERS
Authors: Adam Autry, Ilwoo Park, Hsin-Yu Chen, Jeremy Gordon, Cassie Kline-Nunnally, Daniel Vigneron, Janine Lupo, Yan Li, Duan Xu, Sabine Mueller
Journal: Neuro-Oncology (2019)

INTRODUCTION: As DIPG-tailored therapies become available in the future, the pediatric oncology community will need to address a longstanding issue regarding the lack of imaging biomarkers for evaluating response to treatment. Dynamic hyperpolarized carbon-13 (13C) MR imaging offers a non-invasive means of probing real-time metabolism in vivo and has already been applied in adult patients with glioma (Park et al., MRM 2018; Keshari et al. Cancer Research 2018). The purpose of the current work was to evaluate the feasibility of this technique in pediatric patients and compare metabolism in normal-appearing white matter (NAWM) with adults. METHODS: Six pediatric patients (1 female, 5 males; ages 9–17) previously diagnosed with DIPG (n=3), pineoblastoma (n=1), medulloblastoma (n=1), or adamantinomatous craniopharyngioma (n=1) received dynamic 13C MR imaging exams following intravenous injection of hyperpolarized [1-13C]pyruvate at 1–3 mL/s (0.43mL/kg). MR sequences consisted of either echo-planar imaging or echo-planar spectroscopic imaging, with 3.38-8cm3 spatial resolution and 3s temporal resolution. Pre/post-injection EKGs and continuous vital sign measurements enabled close monitoring of patient response to the hyperpolarized contrast agent. All patients had previous radiation treatment (50-60Gy) and underwent diverse therapies; only 2 patients (DIPG) were surgery-naive. Conversion of [1-13C]pyruvate to [1-13C]lactate was kinetically modeled as a rate constant (kPL) in NAWM using established methodology. RESULTS: There were no adverse effects in patients following injection of [1-13C]pyruvate. The apparent rate constant (kPL) in this pediatric cohort was 0.022±0.007s-1 (range:0.014–0.030s-1), which was similar to adult patients with glioma treated by radiation (0.021±0.005). In one surgery-naïve patient with DIPG who received a higher resolution exam, two adjacent voxels in the T2 lesion demonstrated a 176–220% increase in kPL relative to NAWM. CONCLUSION: Initial results suggest hyperpolarized 13C MR imaging can be safely performed in pediatric patients with CNS cancers and may augment treatment surveillance.
Biological effects of A-371191, a novel Bcl-XL antagonist
Authors: Stephen K. Tahir, Robert B. Warner, Jang Y. Lee, Mary K. Joseph, Haichao Zhang, Paul Nimmer, William J. McClellan, Wang Shen, Saul H. Rosenberg, Shi-Chung Ng
Journal: Cancer Research (2004)

4665   A-371191 represents a benzenesulfonamide derivative developed at Abbott Laboratories as a novel Bcl-X L  antagonist. Bcl-X L  is one of the anti-apoptotic Bcl-2 family members that plays a key role in the regulation of apoptosis. Overexpression of Bcl-X L  occurs in numerous cancers and its overexpression correlates with increased resistance to many chemocytotoxic drugs. A-371191 binding affinity was greater for Bcl-X L  as compared to other Bcl-2 family members using a fluorescent polarization assay. The binding affinity values (k i ) were  L , Bcl-2, Bcl-w and Bcl-b, respectively. A-371191 co-localized with the mitochondrial specific dye MitoTracker in NIH-H460 cells using a BODIPY Texas Red-X, succinimidyl ester labeled A-371191 derivative, suggesting that A-371191 not only accumulated in cells, but it was targeted also to the mitochondria. To test A-371191 activity  in vitro  we used a matched pair of neomycin transfected (HL60/neo) and Bcl-X L  transfected HL-60 human acute myeloid leukemia cells kindly provided by Dr. K. Bhalla (Moffitt Cancer Center, Tampa, FL). We found by Western blot analysis that HL-60/Bcl-X L  cells overexpress Bcl-X L  as compared to HL-60/neo cells, both express a moderate level of Bcl-2, Bax and Bak and undetectable levels of Bcl-w. HL-60/Bcl-X L  cells were less sensitive to a variety of chemocytotoxic agents including paclitaxel, doxorubicin, methotrexate, Gemzar, cisplatin, and etoposide as compared to HL-60/neo cells. HL-60/Bcl-X L  cell sensitivity to cisplatin and doxorubicin was restored similar to the HL-60/neo cells when co-treated with 3.2 and 1.8 μM A-371191, respectively,  in vitro . We tested the  in vivo  efficacy of A-371191 in SCID mice with established HL60/Bcl-X L  i.p. tumors at 75 or 150 mpk, bid, i.p. for 7 days as compared to doxorubicin at 1 mpk qd, i.p. for 5 days. The average control tumor volume was 2435 mm 3  whereas the average tumor volume following 75 mpk A-371191 treatment was 2667 after the 7-day treatment period. On the other hand, the average tumor volume after the 7-day treatment period following 150 mpk A-371191 or 1 mpk doxorubicin treatment was 1742 and 1731 mm 3 , respectively. Thus treatment with 150 mpk A-371191 appeared to be equally effective as treatment with doxorubicin at 1 mpk for 5 days. The one advantage was that the doxorubicin-treated animals lost a statistically significant (p L  antagonists with promising anti-cancer activity both  in vitro  and  in vivo .
Alcohol Intake and Risk of Lethal Prostate Cancer in the Health Professionals Follow-Up Study
Authors: Mary K. Downer, Stacey A. Kenfield, Meir J. Stampfer, Kathryn M. Wilson, Barbra A. Dickerman, Edward L. Giovannucci, Eric B. Rimm, Molin Wang, Lorelei A. Mucci, Walter C. Willett, June M. Chan, Erin L. Van Blarigan
Journal: Journal of Clinical Oncology (2019)

PURPOSE It is unknown whether alcohol intake is associated with the risk of lethal (metastatic or fatal) prostate cancer. We examine (1) whether alcohol intake among men at risk of prostate cancer is associated with diagnosis of lethal prostate cancer and (2) whether intake among men with nonmetastatic prostate cancer is associated with metastasis or death. METHODS This prospective cohort study uses the Health Professionals Follow-Up Study (1986 to 2012). Our analysis of alcohol intake among men at risk of prostate cancer included 47,568 cancer-free men. Our analysis of alcohol intake among men with prostate cancer was restricted to 5,182 men diagnosed with nonmetastatic prostate cancer during follow-up. We examine the association of total alcohol, red and white wine, beer, and liquor with lethal prostate cancer and death. Multivariate Cox proportional hazards regression estimated hazard ratios (HRs) and 95% CIs. RESULTS Alcohol drinkers had a lower risk of lethal prostate cancer (any v none: HR, 0.84 [95% CI, 0.71 to 0.99]) without a dose-response relationship. Total alcohol intake among patients with prostate cancer was not associated with progression to lethal prostate cancer (any v none: HR, 0.99 [95% CI, 0.57 to 1.72]), whereas moderate red wine intake was associated with a lower risk (any v none: HR, 0.50 [95% CI, 0.29 to 0.86]; P trend = .05). Compared with none, 15 to 30 g/d of total alcohol after prostate cancer diagnosis was associated with a lower risk of death (HR, 0.71 [95% CI, 0.50 to 1.00]), as was red wine (any v none: HR, 0.74 [95% CI, 0.57 to 0.97]; P trend = .007). CONCLUSION Cancer-free men who consumed alcohol had a slightly lower risk of lethal prostate cancer compared with abstainers. Among men with prostate cancer, red wine was associated with a lower risk of progression to lethal disease. These observed associations merit additional study but provide assurance that moderate alcohol consumption is safe for patients with prostate cancer.