tbuckley/cabot-search huggingface dataset:
Dynamic Contrast-enhanced MRI Detects Responses to Stroma-directed Therapy in Mouse Models of Pancreatic Ductal Adenocarcinoma
Authors: Jianbo Cao, Stephen Pickup, Cynthia Clendenin, Barbara Blouw, Hoon Choi, David Kang, Mark Rosen, Peter J. O'Dwyer, Rong Zhou
Journal: Clinical Cancer Research (2018)

The dense stroma underlies the drug resistance of pancreatic ductal adenocarcinoma (PDA) and has motivated the development of stroma-directed drugs. Our objective is to test the concept that dynamic contrast-enhanced (DCE) MRI using FDA-approved contrast media, an imaging method sensitive to the tumor microenvironment, can detect early responses to stroma-directed drug.Imaging studies were performed in three mouse models exhibiting high desmoplastic reactions: the autochthonous PDA in genetically engineered mice (KPC), an orthotopic model in syngeneic mice, and a xenograft model of human PDA in athymic mice. An investigational drug, PEGPH20 (pegvorhyaluronidase alfa), which degrades hyaluronan (HA) in the stroma of PDA, was injected alone or in combination with gemcitabine.At 24 hours after a single injection of PEGPH20, Ktrans , a DCE-MRI-derived marker that measures how fast a unit volume of contrast media is transferred from capillaries to interstitial space, increased 56% and 50% from baseline in the orthotopic and xenograft tumors, respectively, compared with a 4% and 6% decrease in vehicle groups (both P < 0.05). Similarly, after three combined treatments, Ktrans in KPC mice increased 54%, whereas it decreased 4% in controls treated with gemcitabine alone (P < 0.05). Consistently, after a single injection of PEGPH20, tumor HA content assessed by IHC was reduced substantially in all three models while drug delivery (measured by paclitaxel accumulation in tumor) was increased by 2.6-fold.These data demonstrated a DCE-MRI marker, Ktrans , can detect early responses to stroma-directed drug and reveal the sustained effect of combination treatment (PEGPH20+ gemcitabine).
Abstract 025: Cross-sectional Relations of Serum Cortisol and Cognitive and Structural Brain Measures in Young Adults: The Framingham Heart Study
Authors: Justin B Echouffo Tcheugui, Sarah Conner, Jayandra J Himali, Pauline Maillard Maillard, Charles S DeCarli, Alexa S Beiser, Ramachandran S Vasan, Sudha Seshadri
Journal: Circulation (2018)

Introduction: Chronic stress and related changes in serum cortisol have adverse effects on brain structure and cognition in animal models. However, evidence from population-based studies is scant. We assessed the association of early morning serum cortisol with cognition and brain structural integrity in middle-aged adults without dementia. Hypotheses: High or low levels of serum cortisol are associated with lower cognitive performance and brain volumes. Methods: We evaluated dementia-free Framingham Study (Generation 3) participants (mean age 48.5 years; 46.8% men), who underwent cognitive testing of memory, abstract reasoning, visual perception, attention, and executive function (n= 2231), and brain MRI (n=2018) to assess total white matter, lobar gray matter, and white matter hyperintensity volumes and fractional anisotropy (FA) measures. We used linear or logistic (cortisol categorized in tertiles, middle tertile as the reference) regression to assess the relations of cortisol with cognition, MRI volumes and voxel-based microstructural white matter integrity and gray matter density, adjusting for age, sex, APOE and vascular risk factors. Results: Higher cortisol (highest tertile vs. middle tertile) was associated with worse memory and visual perception, as well as lower total cerebral brain, occipital and frontal lobar gray matter volumes (Table ) . Higher cortisol was associated with multiple areas of microstructural changes on voxel-based analyses (gray matter density and FA). The association of cortisol with total cerebral brain volume varied by sex ( Pinteraction =0.048 , highest cortisol tertile inversely associated with cerebral brain volume in women [ P= 0.001] but not in men [ P =0.717]). There was no effect modification by the apoE4 genotype of the relations of cortisol and cognition or imaging traits. Conclusions: Higher serum cortisol was associated with lower brain volumes and impaired memory in asymptomatic young adults in their forties; women may be particularly susceptible to this influence.
Abstract 15524: Cardiac Rehabilitation Improves Health Status and Six Minute Walk Distance in Patients With Continuous Flow Left Ventricular Assist Devices
Authors: Celeste T Williams, Dennis Kerrigan, Jonathan K Ehrman, Matthew A Saval, Kyle Bronsteen, John R Schairer, Meghan Swaffer, Clinton A Brawner, David E Lafear, Yelena Selektor, Mauricio Velez, Cristina Tita, Steven Keteyian
Journal: Circulation (2013)

Objective: Continuous-flow left ventricular assist devices (LVAD) show improved patient reported health status (HS) and six-minute walk distance (6MW) within the first 1 to 6 months following impla...
Abstract 15662: Impaired Endothelial Function in Patients With Hypertension Receiving Antihypertensive Drug Treatment Regardless of Achieved Blood Pressure Level:-FMD-J Study
Authors: Tatsuya Maruhashi, Yukihito Higashi, Yumiko Iwamoto, Masato Kajikawa, Shinji Kishimoto, Shogo Matsui, Haruki Hashimoto, Farina B Yusoff, Takayuki Hidaka, Ayumu Nakashima, Kensuke Noma, Yasuki Kihara
Journal: Circulation (2017)

Introduction: Hypertension is associated with endothelial dysfunction. Blood pressure significantly correlates with endothelial function in antihypertensive drug-naive subjects. The purpose of this...
Association of the <i>POT1</i> Germline Missense Variant p.I78T With Familial Melanoma
Authors: Kim Wong, Carla Daniela Robles-Espinoza, David Rodriguez, Saskia S. Rudat, Susana Puig, Miriam Potrony, Chi C. Wong, James Hewinson, Paula Aguilera, Joan Anton Puig-Butille, Brigitte Bressac-de Paillerets, Hélène Zattara, Louise van der Weyden, Christopher D. M. Fletcher, Thomas Brenn, Mark J. Arends, Víctor Quesada, Julia A. Newton-Bishop, Carlos Lopez-Otin, D. Timothy Bishop, Paul W. Harms, Timothy M. Johnson, Alison B. Durham, David B. Lombard, David J. Adams
Journal: JAMA Dermatology (2018)

The protection of telomeres 1 protein (POT1) is a critical component of the shelterin complex, a multiple-protein machine that regulates telomere length and protects telomere ends. Germline variants in POT1 have been linked to familial melanoma, and somatic mutations are associated with a range of cancers including cutaneous T-cell lymphoma (CTCL).
Altered gene expression in response to diesel exhaust particulate matter (SRM 1650a) in MCF-7 cells detected with DNA microarrays.
Authors: Brinda Mahadevan, Channa Keshava, Eric Brooks, Ainsley Weston, William M. Baird
Journal: Cancer Research (2006)

5207  Human exposures to polycyclic aromatic hydrocarbons (PAHs) occurs in the form of complex mixtures. Some of these PAHs are carcinogenic. Standard Reference Material (SRM) 1650a-Diesel particulate matter was determined by the National Institute of Standards and Technology to contain a mixture of specific PAHs and nitro-substituted PAHs. In this study the gene expression patterns were investigated in MCF-7 cells (derived from a human mammary carcinoma) exposed (24h) to SRM 1650a alone or in combination with the carcinogenic PAH benzo[a]pyrene (BP) or dibenzo[a,l]pyrene (DBP). Gene expression was monitored using high density oligonucleotide arrays (Affymetrix U I33A). Exposure of MCF-7 cells to SRM 1650a alone or in combination with BP or DBP resulted in altered gene expression patterns of many RNA species. The data reported here were based on 2-fold up-regulation or down-regulation of genes that were statistically significant (p ≤ 0.05). Global gene expression analysis revealed 30, 127 and 19 genes that were significantly altered in response to SRM 1650a, SRM 1650a plus BP, or DBP, respectively. Functional classification of differentially expressed genes indicated that several of the genes were either directly or indirectly involved in metabolism of PAHs, cell cycle regulation, proliferation, DNA repair and tumor suppression. In a previous study we have shown that CYP1A1 and CYP1B1 were up-regulated on exposure to BP (Cancer Research, 2005, 65:1251-58). In this study, an induction of the same genes was noticed on co-treatment with SRM 1650a plus BP. Unlike SRM 1650a alone or co-treatment with BP, expression of CYP1A1 was not observed when the cells were co-treated with SRM 1650a and DBP, although expression of CYP1B1 was evident. These results not only provide a transcriptional signature to chemical carcinogen exposure, but also assist in the development of specific and sensitive biomarkers for use in studies of exposure and susceptibility, both in mechanistic and epidemiological studies. Supported in part by grant CA28825, NCI, DHHS. Disclaimer: The views expressed in this abstract are those of the authors and do not represent the policies of the U.S. EPA or NIOSH, CDC.
Systematic and combined endosonographic staging of lung cancer (SCORE study)
Authors: Laurence M.M. Crombag, Christophe Dooms, Jos A. Stigt, Kurt G. Tournoy, Olga C.J. Schuurbiers, Maarten K. Ninaber, Wieneke A. Buikhuisen, Sayed M.S. Hashemi, Peter I. Bonta, Daniël A. Korevaar, Jouke T. Annema
Journal: European Respiratory Journal (2018)

Guidelines recommend endosonography for mediastinal nodal staging in patients with resectable nonsmall cell lung cancer (NSCLC). We hypothesise that a systematic endobronchial ultrasound (EBUS) evaluation combined with an oesophageal investigation using the same EBUS bronchoscope (EUS-B) improves mediastinal nodal staging versus the current practice of targeted positron emission tomography (PET)-computed tomography (CT)-guided EBUS staging alone. A prospective, multicentre, international study ( NCT02014324 ) was conducted in consecutive patients with (suspected) resectable NSCLC. After PET-CT, patients underwent systematic EBUS and EUS-B. Node(s) suspicious on CT, PET, EBUS and/or EUS-B imaging and station 4R, 4L and 7 (short axis ≥8 mm) were sampled. For patients without N2/N3 disease determined on endosonography, surgical-pathological staging was the reference standard. 229 patients were included in this study. The prevalence of N2/N3 disease was 103 out of 229 patients (45%). A PET-CT-guided targeted approach by EBUS identified 75 patients with N2/N3 disease (sensitivity 73%, 95% CI 63–81%; negative predictive value (NPV) 81%, 95% CI 74–87%). Four additional patients with N2/N3 disease were found by systematic EBUS (sensitivity 77%, 95% CI 67–84%; NPV 84%, 95% CI 76–89%) and five more by EUS-B (84 patients total; sensitivity 82%, 95% CI 72–88%; NPV 87%, 95% CI 80–91%). Additional clinical relevant staging information was obtained in 23 out of 229 patients (10%). Systematic EBUS followed by EUS-B increased sensitivity for the detection of N2/N3 disease by 9% compared to PET-CT-targeted EBUS alone.
Abstract 17596: Mir-126-5p Promotes Endothelial Cell Proliferation and Limits Lesion Formation During Atherosclerosis by Suppressing Dlk1
Authors: Maliheh Nazari Jahantigh, Yuanyuan Wei, Kathrin Heyll, Judit Corbalan Campos, Jochen Grommes, Shusheng Wang, Eric Olson, Christian Weber, Andreas Schober
Journal: Circulation (2013)

Endothelial cell (EC) function and survival are affected by hyperlipidemia and disturbed laminar flow, which in turn leads to atherosclerosis; endothelial miR-126-3p promotes angiogenesis and reduc...
Structure Guided Engineering of Highly Specific Chimeric Antigen Receptors for the Treatment of T Cell Lymphomas
Authors: Shimobi Onuoha, Mathieu Ferrari, Anna Bulek, Reyisa Bughda, Somayya Manzoor, Saket Srivastava, Biao Ma, Rajesh Karattil, Alex Kinna, Patrycja Wawrzyniecka, Simon Thomas, Shaun P Cordoba, Paul Maciocia, Martin Pule
Journal: Blood (2018)
Use of Computerized Provider Order Entry Events for Postoperative Complication Surveillance
Authors: Brian T. Bucher, Jeffrey P. Ferraro, Samuel R. G. Finlayson, Wendy W. Chapman, Adi V. Gundlapalli
Journal: JAMA Surgery (2018)

Conventional approaches for tracking postoperative adverse events requires manual medical record review, thus limiting the scalability of such efforts.To determine if a surveillance system using computerized provider order entry (CPOE) events for selected medications as well as laboratory, microbiologic, and radiologic orders can decrease the manual medical record review burden for surveillance of postoperative complications.This cohort study reviewed the medical records of 21 775 patients who underwent surgical procedures at a university-based tertiary referral center (University of Utah, Salt Lake City) from July 1, 2007, to August 31, 2017. Patients were included if their case was selected for review by a surgical clinical reviewer as part of the National Surgical Quality Improvement Program. Patients were excluded if they had incomplete follow-up data.Thirty-day postoperative occurrences of superficial surgical site infection, deep surgical site infection, organ space surgical site infection, urinary tract infection, pneumonia, sepsis, septic shock, deep vein thrombosis requiring therapy, and pulmonary embolism, as defined by the National Surgical Quality Improvement Program. A logistic regression model was developed for each postoperative complication using CPOE features as predictors on a development set, and performance was measured on a holdout internal validation set. The models were internally validated using bootstrapping with 10 000 replications to determine the sensitivity, specificity, positive predictive value, and negative predictive value of CPOE-based surveillance system.The study included 21 775 patients who underwent surgical procedures. Among these patients, 11 855 (54.4%) were women and 9920 (45.6%) were men, with a mean (SD) age of 51.7 (16.8) years. Overall, the prevalence of postoperative complications was low, ranging from 0.2% (pulmonary embolism) to 2.6% (superficial surgical site infection). Use of CPOE events to detect patients who experienced at least 1 complication had a sensitivity of 74.8% (95% CI, 71.1%-78.4%), specificity of 86.8% (95% CI, 85.5%-88.3%), positive predictive value of 33.8% (95% CI, 31.2%-36.4%), negative predictive value of 97.5% (95% CI, 97.1%-97.8%), and area under the curve of 0.808 (95% CI, 0.791-0.824). The negative predictive value for individual complications ranged from 98.7% to 100%. Use of CPOE events to screen for adverse events was estimated to diminish the burden of manual medical record review by 55.4% to 90.3%. A CPOE-based surveillance system performed well for both inpatient and outpatient procedures.A CPOE-based surveillance of postoperative complications has high negative predictive value, which demonstrates that this approach can augment the currently used, resource-intensive manual medical record review process.
Effects of Indoor and Ambient Black Carbon and PM2.5 on Pulmonary Function among Individuals with COPD
Authors: Jaime E. Hart, Stephanie T. Grady, Francine Laden, Brent A. Coull, Petros Koutrakis, Joel D. Schwartz, Marilyn L. Moy, Eric Garshick
Journal: Environmental Health Perspectives (2018)

Particulate matter (PM) air pollution has been associated with decreased pulmonary function, but the exposure–response relationship in chronic obstructive pulmonary disease (COPD) patients is uncertain, and most studies have only focused on exposures to ambient pollution.We aimed to assess associations between pulmonary function and indoor and ambient PM [Formula: see text] ([Formula: see text]) and black carbon (BC).Between November 2012 and December 2014, 125 patients with COPD (mean age, 73.4 y) who were not currently smoking and without known indoor BC sources were recruited. Indoor BC and [Formula: see text] were measured in each home for a week in each season, up to four times a year, followed by in-person spirometry pre- and post-bronchodilator. Ambient exposures were available from a central site monitor. Multivariable adjusted mixed effects regression models were used to assess associations scaled per interquartile range (IQR) of exposure.There were 367 study visits; the median (IQR) indoor BC and [Formula: see text] were 0.19 (0.22) [Formula: see text] and 6.67 (5.80) [Formula: see text], respectively. Increasing indoor exposures to BC were associated with decreases in pre-bronchodilator forced expiratory volume in 1 s [Formula: see text] and forced vital capacity (FVC), and [Formula: see text]. For example, in multivariable adjusted models, each IQR increase in indoor BC from the weekly integrated filter was associated with a [Formula: see text] [95% confidence interval (CI): [Formula: see text], [Formula: see text]] decrease in pre-bronchodilator [Formula: see text]. Increases in indoor [Formula: see text] were associated with decreases in [Formula: see text] and FVC of smaller magnitude than those for indoor BC; however, the results were less precise. Ambient BC was not associated with pre-bronchodilator pulmonary function, ambient [Formula: see text] was only associated with decreases in FVC and increases in [Formula: see text], and neither indoor nor ambient BC or [Formula: see text] were associated with post-bronchodilator pulmonary function.Low-level exposures to indoor BC and [Formula: see text], but not ambient exposures, were consistently associated with decreases in pre-bronchodilator pulmonary function. There was no association between exposures and post-bronchodilator pulmonary function. https://doi.org/10.1289/EHP3668.
Recent updates in cancer immunotherapy: a comprehensive review and perspective of the 2018 China Cancer Immunotherapy Workshop in Beijing
Authors: Zihai Li, Wenru Song, Mark Rubinstein, Delong Liu
Journal: Journal of Hematology & Oncology (2018)

The immune system is the hard-wired host defense mechanism against pathogens as well as cancer. Five years ago, we pondered the question if the era of cancer immunotherapy was upon us (Li et al., Exp Hem Oncol 2013). Exciting progresses have been made at all fronts since then, including (1) sweeping approval of six agents by the US Food and Drug Administration (FDA) to block the PD-1/PD-L1 pathway for treatment of 13 cancer types; (2) a paradigm shifting indication of PD-1 and CTLA4 blockers for the management of a broad class of cancers with DNA mismatch repair defect, the first-ever tissue agnostic approval of cancer drugs; (3) real world practice of adoptive T cell therapy with two CD19-directed chimeric antigen receptor T cell products (CAR-T) for relapsed and/or refractory B cell malignancies including acute lymphoid leukemia and diffuse large B cell lymphoma, signaling the birth of a field now known as synthetic immunology; (4) the award of 2018 Nobel Prize in Physiology and Medicine from the Nobel Committee to Tasuku Honjo and James Allison "for their discovery of cancer medicine by inhibition of negative immune regulation" ( www.nobelprize.org/prizes/medicine/2018 ); and (5) the emerging new concept of normalizing rather than amplifying anti-tumor immunity for guiding the next wave of revolution in the field of immuno-oncology (IO) (Sanmamed and Chen, Cell 2018).This article will highlight the significant developments of immune-oncology as of October 2018. The US FDA approved indications of all seven immune checkpoint blockers, and two CD19-directed CAR-T products are tabulated for easy references. We organized our discussion into the following sections: introduction, cell therapy, emerging immunotherapeutic strategies, expediting oncology drug development in an era of breakthrough therapies, new concepts in cancer immunology and immunotherapy, and concluding remarks. Many of these topics were covered by the 2018 China Cancer Immunotherapy Workshop in Beijing, the fourth annual conference co-organized by the Chinese American Hematologist and Oncologist Network (CAHON), China FDA (CFDA; now known as China National Medical Product Administration (NMPA)), and the Tsinghua University. We significantly expanded our discussion of important IO developments beyond what were covered in the conference, and proposed a new Three Rs conceptual framework for cancer immunotherapy, which is to reverse tolerance, rejuvenate the immune system, and restore immune homeostasis. We conclude that the future of immuno-oncology as a distinct discipline of cancer medicine has arrived.
Abstract 17327: Postconditioning Adversely Affects the Outcome of Cardiopulmonary Resuscitation During Untreated Cardiac Arrest
Authors: Wei Wang, Tianfeng Hua, Hao Li, Changqing Miao, Xiaobo Wu, Jennifer Bradley, Mary Ann Peberdy, Joseph P Ornato, Wanchun Tang
Journal: Circulation (2017)

Introduction: Ischemic preconditioning can reduce reperfusion injury in experimental animals, but is not feasible in clinical practice. Moving a preconditioning stimulus to the beginning of reperfusion (post-conditioning) is also effective in animal models. It is unclear if the concept of post-conditioning early during CPR has any benefit. Hypothesis: Brief periods of withholding precordial compression during early CPR will improve resuscitation outcome and post-resuscitation myocardial function. Methods: We randomized 16 male Sprague-Dawley rats weighing 450-550g to: 1) control; 2) ischemic post-conditioning (PC). Ventricular fibrillation was induced and untreated for 8 min. In the control group, precordial compression was uninterrupted for 8 min. In the experimental group, ischemic post-conditioning was induced with 4 cycles of 10 s of chest compressions followed by a 10 s pause initiated at 2 min of chest compression. Ejection fraction (EF) was measured hourly for 4 h and serum troponin I (cnTI) was me...
Development of Quality Measures in Cirrhosis by the Practice Metrics Committee of the American Association for the Study of Liver Diseases
Authors: Fasiha Kanwal, Elliot B. Tapper, Chanda Ho, Sumeet K. Asrani, Nadia Ovchinsky, John Poterucha, Avegail Flores, Victor Ankoma‐Sey, Bruce Luxon, Michael Volk
Journal: Hepatology (2018)

Health care delivery is increasingly evaluated according to quality measures, yet such measures are underdeveloped for cirrhosis. The Practice Metrics Committee of the American Association for the Study of Liver Diseases was charged with developing explicit process‐based and outcome‐based measures for adults with cirrhosis. We identified candidate measures from comprehensive reviews of the literature and input from expert clinicians and patient focus groups. We conducted an 11‐member expert clinician panel and used a modified Delphi method to systematically identify a set of quality measures in cirrhosis. Among 119 candidate measures, 46 were identified as important measures to define the quality of cirrhosis care, including 26 process measures, 7 clinical outcome measures, and 13 patient‐reported outcome measures. The final process measures captured care processes for ascites (n = 5), varices/bleeding (n = 7), hepatic encephalopathy (n = 4), hepatocellular cancer (HCC) screening (n = 1), liver transplantation evaluation (n = 2), and other care (n = 7). Clinical outcome measures included survival, variceal bleeding and rebleeding, early‐stage HCC, liver‐related hospitalization, and rehospitalization within 7 and 30 days. Patient‐reported outcome measures covered physical symptoms, physical function, mental health, general function, cognition, social life, and satisfaction with care. The final list of patient‐reported outcomes was validated in 79 patients with cirrhosis from nine institutions in the United States. Conclusion: We developed an explicit set of evidence‐based quality measures for adult patients with cirrhosis. These measures are a tool for providers and institutions to evaluate their care quality, drive quality improvement, and deliver high‐value cirrhosis care. The quality measures are intended to be applicable in any clinical care setting in which care for patients with cirrhosis is provided.