tbuckley/cabot-search huggingface dataset:
Abstract 20958: Smyd1a Overexpression Suppresses Functional Decline in the Adult Myocardium
Authors: Marta Szulik, Li Wang, June Garcia-Llana, Christopher Tracy, Sarah Franklin
Journal: Circulation (2017)

Heart disease is the leading cause of death in the United States. This chronic condition affects the heart so it can no longer sufficiently pump blood to vital organs in the body. While heart disease can manifest in many different ways the general pathophysiology is conserved: the heart compensates for an increased workload by undergoing hypertrophic growth, accompanied by transcriptional reprogramming, and progresses into heart failure. Although many epigenetic factors have been identified which influence these underlying changes in transcription during disease, we still know very little about how this process is regulated in the cardiomyocyte. Smyd1, a unique histone methyltransferase that regulates gene expression in the cardiomyocyte, was originally shown to play a crucial role in early cardiac development. More recently, we have shown that loss of Smyd1 in the adult mouse heart leads to pro-hypertrophic signaling resulting in cardiomyocyte growth, fibrosis and functional decline. In addition, we examined the two Smyd1 isoforms (Smyd1a and Smy1b) in isolated myocytes and showed that Smyd1a (but not Smyd1b) overexpression (OE) was capable of inhibiting phenylephrine-induced hypertrophy. To further characterize the role of Smyd1 in the myocardium and determine if Smyd1a is capable of inhibiting hypertrophic growth in adult heart we generated transgenic mice capable of inducible, cardiac-specific OE of Smyd1a using a Tet-On system. Mice were fed doxycycline-laced chow for 2 weeks to achieve Smyd1a-OE at which time we characterized their cardiac phenotype under basal conditions and after stress (permanent occlusion). Interestingly, transgenic mice showed no observable difference under basal conditions, however, 3 weeks after permanent occlusion of the LAD, the EF of wild type animals decreased to ~37%, while transgenic mice maintained an EF of ~61% . In addition, transgenic mice exhibited exacerbated growth (12% increase in HW/BW ratio) with no change in expression of the hypertrophic marker ANF, in contrast to wild type animals (4 fold increase). These exciting results suggest that Smyd1a is capable of preserving cardiac function in adult mice, however, this mechanism appears to be independent of hypertrophic signaling.
The motivation to sacrifice for a cause reflects a basic cognitive bias
Authors: Christopher Y Olivola
Journal: Behavioral and Brain Sciences (2018)

Abstract Many extreme forms of self-sacrifice occur without identity fusion or out-group threats. For example, people willingly participate in extreme charity fundraisers – exerting effort, enduring pain, and risking bodily injury – to advance desired causes. Therefore, it seems plausible that the motivation to engage in extreme self-sacrifice reflects a basic cognitive bias, rather than an evolutionary-cultural adaption specifically designed for intergroup conflict.
Environmental Management of Asthma in Clinical Practice: Results from the National Ambulatory Medical Care Survey
Authors: Paivi M. Salo, Lara J. Akinbami, Michelle M. Cloutier, Jesse C. Wilkerson, Lydia Feinstein, Kurtis S. Elward, Jacek M. Mazurek, Gregory B. Diette, Tracey A. Mitchell, Sonja Williams, Darryl C. Zeldin
Journal: Journal of Allergy and Clinical Immunology (2019)
Therapeutic switch from omalizumab to mepolizumab in patients with uncontrolled severe eosinophilic asthma: treatment effect by prior omalizumab treatment duration
Authors: Frank Albers, Mark C. Liu, Bradley E. Chipps, Kenneth R. Chapman, Xavier Muñoz, Miguel Bergna, Gilles Devouassoux, Jay Azmi, Robert Price, Dmitry Galkin
Journal: Journal of Allergy and Clinical Immunology (2019)
The HAS-RISC Score for Venous Thromboembolism (VTE) Risk Stratification in Newly Diagnosed Multiple Myeloma Patients Starting Immunomodulatory Drugs (IMID)
Authors: Ang Li, Qian V. Wu, Greg Warnick, Neil A Zakai, Edward N. Libby, David A. Garcia, Gary H. Lyman
Journal: Blood (2018)
Quantifying the evolution of tumor architecture using serial circulating tumor DNA.
Authors: Jason Henry, Jonathan M. Loree, John H. Strickler, Kanwal Pratap Singh Raghav, Van K. Morris, Victoria M. Raymond, Richard B. Lanman, Rona Yaeger, Ryan Bruce Corcoran, Michael J. Overman, Scott Kopetz
Journal: Journal of Clinical Oncology (2019)

600 Background: There is limited data regarding changes in the genomic landscape in individual patients over time as serial tissue biopsy has risk and is of uncertain clinical benefit. The advent of circulating tumor DNA (ctDNA) allows for safe and repeated molecular sampling with the potential to investigate evolution of tumor architecture over the disease course. Methods: From 5/15 to 12/17, 116 patients with metastatic CRC had between three to 12 blood specimens taken over the treatment course. Plasma was tested using targeted NGS assay (Guardant360, Guardant Health, 68 gene). To account for variations in the amount of ctDNA in serial samples, a window of evaluable allele frequency was established for each patient as the fold change between the max allele frequency (mAF) and limit of detection for serial samples with the lowest mAF. Mutations not falling within this window were excluded from analysis. Substantial treatment induced selective pressure (SP) was defined as a decrease in the mutant mAF of &gt; 50% in patients with at least an initial mAF of 1%. Results: 116 patients with a total of 317 serial blood samples were evaluable after accounting for ctDNA variations over time. Specimens were collected a median of 12 months apart, with a median of three specimens per patient. Thirteen patients (11%) did not have any changes in mutations on serial sampling, however the remainder of patients gained an average of 1.1 mutations per time point (mut/tp), and lost 1.0 mut/tp. 31% of patients demonstrated evidence of substantial treatment-induced SP. These patients were more likely to demonstrate a change in clonal architecture of the tumor (46% greater rate than those without SP, P = 0.04), predominantly through gain of new clones. In contrast, clonal hematopoiesis alterations that may be induced by chemotherapy, such as JAK2 V617F , were neither gained or lost. Conclusions: After correction for variations over time in the total amount of ctDNA in circulation, we identify numerous changes in tumor architecture with serial sampling. For the first time in colorectal cancer we demonstrate that when treatment-induced SP is applied the rate of tumor evolution is increased, demonstrating potential value of monitoring changes in tumor architecture over the disease course.
IL-17A and IL-4/IL-13 Exert Distinct Changes in Skin Lipids
Authors: Elena Goleva, Elizabeth H. Tham, John Jung, Byung Eui Kim, Kathryn A. Norquest, Anna S. Bronoff, Irina Bronova, Donald Y.M. Leung, Evgeny Berdyshev
Journal: Journal of Allergy and Clinical Immunology (2019)
CLINICAL AND LABORATORY EVALUATION OF PATIENTS WITH COMMON VARIABLE IMMUNODEFICIENCY (CVID)
Authors: Isabella B. Manhaes, Gabriele F. Camilo, Barbara Luiza B. Cancado, Julio Cesar Gontijo, Renan Augusto Pereira, Marília M. Moraes, Luiza M. Marino, Sandro F. Perazzio, Carolina S. Aranda, Juliana Themudo Lessa Mazzucchelli, Dirceu Sole, Beatriz Tavares Costa-Carvalho
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 14584: Noninvasive Estimation of Time Constant of Left Ventricular Pressure Decline as an Index of Relaxation by Speckle Tracking Echocardiography; Validation Study by Cardiac Catheterization
Authors: Itta Kawamura, Masanori Kawasaki, Ryuhei Tanaka, Takashi Yoshizane, Takashi Kato, Maki Saeki, Maki Nagaya, Koji Ono, Makoto Iwama, Masazumi Arai, Yoshiaki Kawase, Munenori Okubo, Akihiko Tsuchiya, Shinji Tomita, Hitoshi Matsuo, Toshiyuki Noda, Takahiko Suzuki, Hiroshige Ohashi, Sachiro Watanabe, Shinya Minatoguchi
Journal: Circulation (2016)

Background: There has been no established echo parameter to accurately assess left ventricular (LV) relaxation as diastolic function. LV relaxation assessed by time constant of LV pressure decline (Tau) using left heart catheterization is reported to be deteriorated even in the early stage of hypertension. Thus, it is important to noninvasively evaluate LV relaxation in various cardiac diseases. We sought to noninvasively estimate Tau (eTau) by speckle tracking echocardiography (STE) and to validate eTau by Tau measured by cardiac catheterization. Methods: Isovolume relaxation time (IVRT) was reported to be measured as the time between end of LV outflow wave and beginning of inflow wave by Doppler echo. We reported that pulmonary capillary wedge pressure (ePCWP) was accurately estimated as 10.8 - 12.4 x Log (left atrial active emptying function / minimum left atrial volume) by STE. Thus, the eTau by echo was obtained using the formula: eTau = IVRT / (ln 0.9 x systolic blood pressure - ln ePCWP). Echo para...
Abstract 18120: High Density Lipoprotein Particles Predict All-cause and Cardiovascular Mortality
Authors: Günther Silbernagel, Philipp Pagel, Volker Pfahlert, Bernd Genser, Hubert Scharnagl, Marcus E Kleber, Graciela Delgado, Andreas Ritsch, Tanja B Grammer, Iris Baumgartner, Wolfgang Koenig, Winfried März
Journal: Circulation (2015)

Introduction: The concentration and size of HDL particles are considered to be related to their atheroprotective properties. This study in patients at increased cardiovascular risk was performed to evaluate the associations of HDL particle characteristics with all-cause and cardiovascular mortality. Methods and Results: HDL particle concentrations for all sizes and for size categories (7-8.5 nm, 8.5-10 nm, 10-13 nm, and 13-16 nm) were measured in 2,290 participants of the LURIC study (1,575 males, 715 females) by nuclear magnetic resonance spectroscopy. Mean (standard deviation) age was 62.9 (10.4) years, body mass index was 27.6 (4.1) kg/m 2 , HDL cholesterol was 39 (11) mg/dl, and HDL particle concentration for all sizes was 25.1 (6.0) μmol/l. During a median (interquartile range) follow-up of 10.0 (6.1-10.6) years, 662 participants died from any cause and 434 from cardiovascular diseases. In multivariable analyses including adjustment for HDL cholesterol tertiles of HDL particle concentrations for all sizes were inversely related to all-cause (3 rd vs. 1 st tertile: HR [95%CI] = 0.69 [0.55-0.87], P=0.001) and cardiovascular mortality (HR [95%CI] = 0.67 [0.50-0.89], P=0.007). These associations were primarily mediated by the inverse relationship between the smallest HDL particles (7-8.5 nm) and endpoints (P≤0.005). The associations of larger HDL particles (8.5-10 nm, 10-13 nm, and 13-16 nm) with endpoints were less pronounced and did not reach statistical significance in multivariable analyses (all P&gt;0.1). Conclusions: In participants of the LURIC study high concentrations of HDL particles predict decreased cardiovascular risk. This association is mainly driven by small HDL particles.
Abstract 18636: Acute Aortic Valve Endocarditis: Long-term Results of the Ross Procedure, Bioprothetic or Mechanical Valve Replacement
Authors: Valentin Loobuyck, Francis Juthier, Natacha Rousse, Agnes Mugnier, Marie Jungling, Anne Ringle, Sylvestre Marechaux, Augustin Coisne, Emmanuel Robin, Marjorie Richardson, Alain Prat, Andre Vincentelli
Journal: Circulation (2017)

Introduction: Acute aortic valve endocarditis (IE) is a severe disease, with an early mortality rate ranging from 15% to 20%. In young adults, the choice of valvular substitute remains controversial. Hypothesis: The objective of our study was to compare the outcome of the surgical treatment of acute aortic IE in young adults using the Ross procedure, a bioprosthesis or a mechanical prosthesis replacement. Methods: From 1994 to 2016, we retrospectively included 105 adult patients under 50 years of age, who underwent surgical treatment of an IE. Mean age was 41 years (32-46), mostly men (88%). Our primary composite endpoint was the event-free survival (death, recurrence of IE, reoperation, severe haemorrhagic or thromboembolic event). Ross procedure were performed in 32 patients, bioprosthesis were implanted in 35 patients and mechanical prosthesis in 38 patients. Results: Hospital mortality rate was 7% with no significant differences according to the type of surgical procedure. The 10-year event-free survi...
Designing clinical trials in 3L+ pancreatic cancer.
Authors: Victoria G. Manax, Valery Chatikhine, Saundra Kirven, Ben R Taylor
Journal: Journal of Clinical Oncology (2019)

226 Background: An increasing percentage of pancreatic cancer (PC) patients are looking for 3L+ options. As patient outcomes are improving with advances in treatment for PC, more patients need 3L+ treatments. Few trials focus on this patient segment as evaluation of drug effects can be complicated by comorbidity rates and disease-related SAEs. Having exhausted SOC chemotherapy backbones, patients increasingly search for novel therapies and clinical trial options. This assessment was to evaluate 3L+ PC trials for 1) sufficient patient interest, 2) a clinically evaluable patient population, and 3) guidelines/restrictions that could improve clinical assessment. Methods: Initiated as a retrospective evaluation of consenting patients screened for a prospective 2L+ pancreatic cancer Phase II trial with SM-88. A comparison of recurrent PC trials was performed by Novella to assess industry wide enrollment characteristics. Results: 32% of patients searching for clinical trials YTD 2018 in PanCAN’s database were looking for 3L+ treatments, up from 25% in 2016. In the sample trial, rate of consents (n=72) increased hyperbolically, reaching ~1/pt/day by end of analysis (24 sites). Inc/exc criteria were broadly standard for sponsor-initiated trials, however ECOG PS 2 were eligible. 38% screen failed, with hepatic labs (esp Alb &amp; ALP) as most common reason. Industry analysis indicated expected 0.35 p/s/m for refractory PC trials and 20% screen fail. 93% (37/40) of SAEs were unrelated to study drug, including 11 G4 or G5 prior to receiving drug. Preliminary safety and efficacy results for the trial are reported elsewhere. Conclusions: Rapid enrollment from 3L+ patients demonstrated significant interest among this patient segment. The screen failure rate was within reasonable expectations, implying a majority of the patients were within standard inc/exc criteria. The high level of unrelated SAEs during the consent period and initial enrollment period indicate this may not be a suitable population to properly assess drug safety. Subgroup statistical analyses may be more relevant than ITT medians since several comorbidities, such as biliary obstruction, have elsewhere been demonstrated to have a dramatic impact on OS. Clinical trial information: NCT03512756.
Treatment Facility Volume and Outcomes in Waldenstrom Macroglobulinemia
Authors: Jonas Paludo, Jithma Prasad Abeykoon, Stephen M. Ansell, Morie A. Gertz, Prashant Kapoor, Aneel Paulus, Sikander Ailawadhi, Craig B. Reeder, Thomas E. Witzig, Thomas M. Habermann, Anne J Novak, Francis K. Buadi, Angela Dispenzieri, Yi Lin, Martha Q. Lacy, Shaji K. Kumar, S. Vincent Rajkumar, Robert A. Kyle, Ronald S. Go
Journal: Blood (2018)
Specific and Targetable Interactions with the Bone Marrow Microenvironment Govern Outcome in Imatinib-Resistant Chronic Myeloid Leukemia
Authors: Rahul Kumar, Maximilian Marten, Valentina Minciacchi, Raquel Pereira, Costanza Zanetti, Nina Hyduk, Thomas Oellerich, Hans Michael Kvasnicka, Joel Spencer, Frank Schnuetgen, Charles Lin, Cristina Lo Celso, Melanie Meister, Franck Emmanuel Nicolini, Daniela S. Krause
Journal: Blood (2018)
Secukinumab drug survival in patients with psoriasis: A multicenter, real-world, retrospective study
Authors: Tiago Torres, Anna Balato, Curdin Conrad, Andrea Conti, Paolo Dapavo, Paulo Ferreira, Francesca Gaiani, Luíz Leite, Piergiorgio Malagoli, Pedro Mendes-Bastos, Matteo Megna, Francesco Messina, Alessia Nidegger, Giulia Odorici, Stefano Piaserico, Francesca Prignano, Simone Ribero, Federica Ricceri, Annalisa Tonini, Joana Valério, Andrea Chiricozzi
Journal: Journal of the American Academy of Dermatology (2019)
Abstract 303: End-Tidal CO2 Reactivity Is Associated with Defibrillation Success
Authors: Ruchika D Husa, Owen Bowers, Rebecca Sell, Dorothy Scyoc, Anush Minokadeh, Daniel Davis
Journal: Circulation (2012)

Background: High quality cardiopulmonary resuscitation (CPR) appears to modulate ventricular fibrillation (VF) morphology and increase defibrillation success. However, VF waveform analysis has not proven to be clinically effective in guiding resuscitation. End-tidal CO2 (PetCO2) correlates well with cardiac perfusion during CPR. Objective: To evaluate PetCO2 as a predictor of defibrillation success. Methods: This was a prospective, observational study conducted at two urban academic hospitals with a combined total of 500 beds. Data regarding defibrillation attempts, CPR process, and PetCO2 were abstracted from monitor/defibrillators. All arrest victims with primary VF or ventricular tachycardia (VT) for whom CPR and PetCO2 data were available were included in this analysis. Patients with return of spontaneous circulation (ROSC) were compared to those without ROSC with regard to the change in PetCO2, mean and final compression rate and depth, and chest compression fraction (CCF). Results: A total of 32 patients were included in this analysis; 19 of these (59%) had ROSC. PetCO2 values prior to the final defibrillation attempt were 121% higher than initial PetCO2 values in patients with ROSC versus only 19% higher in patients without ROSC (p&lt;0.01). Patients with and without ROSC were similar with regard to mean compression depth (2.5 vs. 2.7 inches, p=NS), final compression depth (2.7 vs. 2.8 inches, p=NS), mean compression rate (119/min for both, p=NS), final compression rate (121/min vs. 123/min, p=NS), mean CCF (83% vs. 85%, p=NS), and final CCF (83% vs. 91%). Conclusions: An increase in PetCO2 was associated with ROSC among inpatients with VF/VT arrest. No differences with regard to overall or final CPR process measures were observed. The “PetCO2 responsiveness” to CPR may reflect an underlying physiology that predicts defibrillation success.
Abstract P261: Genome-wide Association Study of Susceptibility to Particulate Matter-associated Reduced Heart Rate Variability
Authors: Rahul Gondalia, Christy L Avery, Melanie D Napier, Raúl Méndez Giráldez, James D Stewart, Colleen M Sitlani, Yun Li, Jeffrey Roach, Kari E North, Alex P Reiner, Zhu-Ming Zhang, Lesley Tinker, Duanping Liao, Eric A Whitsel, MOPMAP Investigators
Journal: Circulation (2016)

Background: Heart rate variability (HRV) is a heritable electrocardiographic measure of cardiac autonnomic control that is consistently and inversely associated with ambient particulate matter (PM) air pollution and risk of both incident cardiovascular disease, and death. However, genetic susceptibility to PM-associated decreases in HRV has not been characterized. Methods: To characterize such susceptibility in a genome-wide context, we conducted cohort-, race/ethnicity-, and sex-stratified longitudinal analyses of ten Women’s Health Initiative clinical trials and Atherosclerosis Risk in Communities Study subpopulations (total n: 27,121; mean age: 64.6 yr; 81% female; 25% black; 7% Hispanic; mean visits/person: 2.5). In each subpopulation, we log-transformed three previously validated and reliable measures of HRV: RR interval duration (RR); root mean square of successive differences in normal-to-normal RR (RMSSD); and standard deviation of normal-to-normal RR (SDNN). We also estimated mean concentrations of PM &lt; 10 μm on the day of and before HRV measurement. We then used generalized estimating equations (GEE) methods adapted for low prevalence exposure to leverage the repeated measures of HRV and PM10. The GEE models estimated interactions between approximately 2.5 million single nucleotide polymorphisms (SNPs) and PM10 concentrations dichotomized at subpopulation-specific 90th percentiles, while adjusting for age, geographic region or center, season, calendar year, and ancestry. We combined the SNP x PM10 interaction estimates in a Bayesian meta-analysis accounting for ancestral heterogeneity to identify trans-ethnic interactions exceeding genome-wide thresholds: log10 Bayes Factor (BF) &gt; 6 and posterior probability of heterogeneity (PHet) &lt; 0.5. Results: Preliminary analyses of RMSSD provided suggestive evidence of a trans-ethnically important interaction at five SNPs on one locus. The lead SNP (rs17809071; T allele frequency range: 3-16%) is located on chromosome 4, 120 kilobases downstream from SPRY1 (log10BF = 5.31; PHet = 0.14). SPRY1 encodes sprouty receptor tyrosine kinase signaling antagonist 1 which is expressed in cardiac fibroblasts, antagonizes cytokine-induced epicardial fibrosis, and inhibits adipogenesis. Conclusions: Findings from this genome-wide association study of SNP x PM10 interactions suggest that genetic factors may affect susceptibility to PM10-associated decreases in HRV among racially/ethnically diverse populations of men and women protected by the U.S. Environmental Protection Agency under the Clean Air Act.
Clinical outcome of pancreatic cancer patients with indeterminate pulmonary nodules.
Authors: Austin G Kazarian, Sarah L Mott, Carlos Hou Fai Chan
Journal: Journal of Clinical Oncology (2019)

220 Background: Indeterminate pulmonary nodules (IPNs) are often found on staging CT scans for pancreatic cancer and pose a treatment conundrum since resection is contraindicated in metastatic setting. Here we aim to determine the clinical outcome of pancreatic cancer patients with IPNs undergoing curative resection. Methods: Retrospective analysis of 1,182 pancreatic cancer patients in the institutional Oncology Registry between 2007 and 2017 was conducted. Survival probabilities were estimated using the Kaplan-Meier method. Time was calculated from diagnosis to death for overall survival (OS), and from operation to recurrence for recurrence-free survival (RFS). Cox regression models were used to assess the effects of demographic, clinicopathologic, and treatment variables on OS and RFS. Results: IPNs were found in 50 patients undergoing surgery (43 pancreatoduodenectomy, 7 distal pancreatectomy). Negative margins were obtained in 82% of patients. Six and 44 patients had stage 0/I and stage II disease, respectively. Twelve and 35 patients received neoadjuvant and adjuvant therapy, respectively. Over a median follow-up of 20 months from the time of diagnosis, 37 patients (74%) developed local recurrence or distant metastasis in liver (38%), lung (32%), peritoneum (8%), or other sites (8%). Median RFS was 14 months and median OS was 23 months. Tumor size (HR 1.56, CI 1.23-1.98, p &lt; 0.01) and elevated pre-operative CA19-9 (HR 2.51, 1.22 – 5.15, p = 0.01) were associated with lower RFS. Tumor size (HR 1.43, CI 1.10-1.86, p &lt; 0.01) and diabetes (HR 2.05, CI 1.02-4.11, p = 0.04) were associated with lower OS. Patients with lung only recurrence tended to have superior OS relative to other single sites (HR 2.05, CI 0.66-6.33, p = 0.21) or multiple sites (HR 2.30, 0.75-7.50, p = 0.15). Patients with lung only recurrence had a median survival after recurrence of 17.9 months compared to 6.5 months for other single sites or 4.3 months for multiple sites. Conclusions: Only a portion of IPNs develop into true lung metastasis and that isolated lung metastatic recurrence may confer a better survival over metastasis of other sites. Ongoing efforts will identify serum biomarkers to predict recurrence in the hopes of guiding future clinical practice.