tbuckley/cabot-search huggingface dataset:
Landscape and evolution of tissue-specific alternative polyadenylation across Drosophila species
Authors: Piero Sanfilippo, Jiayu Wen, Eric C. Lai
Journal: Genome biology (2017)

Drosophila melanogaster has one of best-described transcriptomes of any multicellular organism. Nevertheless, the paucity of 3′-sequencing data in this species precludes comprehensive assessment of alternative polyadenylation (APA), which is subject to broad tissue-specific control. Here, we generate deep 3′-sequencing data from 23 developmental stages, tissues, and cell lines of D. melanogaster, yielding a comprehensive atlas of ~ 62,000 polyadenylated ends. These data broadly extend the annotated transcriptome, identify ~ 40,000 novel 3′ termini, and reveal that two-thirds of Drosophila genes are subject to APA. Furthermore, we dramatically expand the numbers of genes known to be subject to tissue-specific APA, such as 3′ untranslated region (UTR) lengthening in head and 3′ UTR shortening in testis, and characterize new tissue and developmental 3′ UTR patterns. Our thorough 3′ UTR annotations permit reassessment of post-transcriptional regulatory networks, via conserved miRNA and RNA binding protein sites. To evaluate the evolutionary conservation and divergence of APA patterns, we generate developmental and tissue-specific 3′-seq libraries from Drosophila yakuba and Drosophila virilis. We document broadly analogous tissue-specific APA trends in these species, but also observe significant alterations in 3′ end usage across orthologs. We exploit the population of functionally evolving poly(A) sites to gain clear evidence that evolutionary divergence in core polyadenylation signal (PAS) and downstream sequence element (DSE) motifs drive broad alterations in 3′ UTR isoform expression across the Drosophila phylogeny. These data provide a critical resource for the Drosophila community and offer many insights into the complex control of alternative tissue-specific 3′ UTR formation and its consequences for post-transcriptional regulatory networks.
Abstract 12895: Characteristics and Outcome of Ventricular Tachycardia in Advanced Fabry Disease Cardiomyopathy
Authors: Daniel Oder, Dan Liu, Kai Hu, Tim Salinger, Frank Weidemann, Georg Ertl, Christoph Wanner, Peter Nordbeck
Journal: Circulation (2016)

Introduction: Ventricular tachycardia (VT) are suspected the leading cause of premature death in patients with advanced Fabry cardiomyopathy. However, origin and outcome of respective tachyarrhythmic events have yet not been comprehensively investigated. Methods: All patients (n=261) in care at the Fabry Center for Interdisciplinary Therapy (FAZIT) Würzburg, Germany, with history of (n=17) or demand for (n=1) implantable cardioverter defibrillator (ICD) device therapy for primary or secondary prevention of ventricular tachyarrhythmic events due to advanced Fabry cardiomyopathy underwent comprehensive clinical investigations including analysis of 12-lead ECG, 24-hour Holter ECG, and ICD Holter chart reviews for documented VT episodes with special focus on characteristics and outcome of respective events. Results: Study subjects were mainly of male gender (14/18, 78%) and middle aged (55±10 years, range 33-74) at point of ICD demand. In total, 11/18 patients (61%) suffered from at least one episode of VT. All documented episodes were sustained monomorphic ventricular tachycardia. Most 12-lead ECG documented VT events (n=7) were self-terminated (n=6, 86%). Five subjects were in need of anti-tachycardia overdrive pacing and four of shocks for termination of respective VT events when followed over time. Analyzing VT episodes documented in 12-lead ECG showed a correlation of VT episode origination from the area of myocardial replacement fibrosis, mostly from the postero-lateral wall segments of the left ventricle. Radiofrequency catheter ablation was performed in three patients (17%), of whom two still suffered from VT episodes afterwards and both finally died due to end-stage heart failure complications. Three other subjects from this group also died due to cardiac events (in total 4/18, 22%), whereas one (6%) due to Fabry-associated stroke. Conclusions: VT is common in advanced Fabry disease. As all documented VT episodes were monomorphic, radiofrequency catheter ablation might represent a yet underestimated therapy option besides ICD device therapy. However, due to end-stage heart failure associated complications, cardiac mortality remains a substantial factor questioning the clinical impact and benefit in end-stage Fabry disease.
Abstract 14726: Right Ventricular Strain Analysis May Be Useful in Differentiating Takotsubo Cardiomyopathy From Left Anterior Descending Coronary Artery Disease
Authors: LiYing Cai, Karima Addetia, Victor Mor-Avi, Kirk Spencer
Journal: Circulation (2015)

Background: Takotsubo cardiomyopathy (TTC) is a transient form of left ventricular (LV) dysfunction triggered by significant physiological stress and associated with a distinctive pattern of regional LV dysfunction on echocardiography. This pattern can be similar to and therefore difficult to differentiate from that seen in left anterior descending coronary artery (LAD) occlusion. We hypothesized that right ventricular (RV) involvement as detected by RV free-wall longitudinal strain (FWLS) might help differentiating TCC from LAD infarction. Methods: 44 patients with TTC and 36 with LAD infarct were studied. The RV focused view was used to measure TAPSE (M-mode), S’ (pulsed-wave Doppler), and fractional area change (FAC). RVFWLS was measured offline (Epsilon). Apical 2-, 3- and 4-chamber views were used to measure LV longitudinal strain (LS) (QLAB) and biplane Simpsons was used to assess LV ejection fraction (EF). Results: LVEF was 31±10% in TTC and 41±9% in the LAD group. There was no significant difference in global LV LS between the two groups. Regional differences were noted with lower strain values in the mid and apical inferior, posterior and lateral segments in TTC. RV FAC, TAPSE, and S’ were lower in the TTC group than the LAD group. Overall RV FWLS was significantly lower in TTC than LAD infarct group (-18±8 vs -23±6%, p&lt;0.05). This was due to marked reduction in apical LS (-10±8 vs -15±7%; p=0.002) with no significant differences in mid and basal LS (-19±11 vs -23±9% and -26±13 vs -30±12%, respectively). ROC analysis showed apical RVFWLS to be the best predictor for TTC with area under the curve (AUC) 0.73 (Fig). Conclusion: The regional pattern of RV dysfunction as assessed by FWLS revealed predominately reduction in the apical segments, and sparing of function in the mid and basal segments. Our results suggest that RV involvement should be more carefully evaluated in clinical practice when TTC is suspected as it may help differentiate this condition from LAD disease.
Abstract 17277: Trends of Emergency Department Visits for Non Specific Chest Pain in USA: Analysis of National Emergency Department Sample Database From 2006 to 2013
Authors: Vidhu Anand, Chadi Alraies, Michael Schnaus, Ganesh Raveendran
Journal: Circulation (2016)

Background: Non-specific chest pain (NSCP), or chest pain without an ischemic etiology, is fifth most common reason for Emergency Department (ED) visits in USA. At present, there are no comprehensi...
Iron Oxide Nanoparticles: Innovative Tool in Cancer Diagnosis and Therapy
Authors: Pavla Martinkova, Martin Brtnicky, Jindrich Kynicky, Miroslav Pohanka
Journal: Advanced Healthcare Materials (2017)

Abstract Although cancer is one of the most dangerous and the second most lethal disease in the world, current therapy including surgery, chemotherapy, radiotherapy, etc., is highly insufficient not in the view of therapy success rate or the amount of side effects. Accordingly, procedures with better outcomes are highly desirable. Iron oxide nanoparticles (IONPs) present an innovative tool—ideal for innovation and implementation into practice. This review is focused on summarizing some well‐known facts about pharmacokinetics, toxicity, and the types of IONPs, and furthermore, provides a survey of their use in cancer diagnosis and therapy.
Efficacy of Intravenous Furosemide Versus a Novel, pH-Neutral Furosemide Formulation Administered Subcutaneously in Outpatients With Worsening Heart Failure
Authors: Nisha A. Gilotra, Oluseyi Princewill, Bonnie Marino, Ike S. Okwuosa, Jessica Chasler, Johana Almansa, Abby Cummings, Parker Rhodes, Julianne Chambers, Kimberly Cuomo, Stuart D. Russell
Journal: JACC Heart Failure (2017)

This study sought to determine the efficacy and safety of a novel, pH-neutral formulation of furosemide administered subcutaneously (SC) for treatment of acute decompensated heart failure (HF). Congestion requiring intravenous (IV) administration of a diuretic agent is the main reason patients with HF present for acute medical care. Outpatients presenting with decompensated HF were randomized to receive a single SC or IV dose of furosemide. Primary outcome was 6-h urine output, and secondary outcomes were weight change, natriuresis, and adverse events. Forty-one patients were randomized: 19 were treated with IV (mean dose: 123 ± 47 mg) and 21 with SC furosemide (fixed dose of 80 mg over 5 h). The 6-h urine output in the IV group was not significantly different from that in the SC furosemide group (median IV: 1,425 ml; interquartile range [IQR]: 1,075 to 1,950 ml; vs. median SC: 1,350 ml; IQR: 900 to 1,900 ml; p = 0.84). Additionally, mean weight loss was not significantly different (−1.5 ± 1.1 kg in the IV group vs. −1.5 ± 1.2 kg in the SC group; p = 0.95). Hourly urine output was significantly higher in the IV group at hour 2 (425 ml in the IV group vs. 250 ml in the SC group; p = 0.02) and higher in the SC group at hour 6 (125 ml, IV group vs. 325 ml, SC group; p = 0.005). Natriuresis was higher in the SC group (IV: 7.3 ± 35.3 mEq/l vs. SC: 32.8 ± 43.6 mEq/l; p = 0.05). There was no worsening renal function, ototoxicity, or skin irritation with either formulation. Thirty-day hospitalization rates were similar. In this phase II trial, we did not identify significant differences between urine output obtained with pH-neutral furosemide administered SC and that obtained by IV. This method of decongestion may allow treatment at home and reduced HF resources and warrants further investigation. (Sub-Q Versus IV Furosemide in Acute Heart Failure; NCT02579057)
Abstract 16987: Increased Ischemic Heart Disease And Stroke-related Hospitalizations From Cold Temperature in Ontario, Canada: Population-based Study
Authors: Hong Chen, Qiongsi Li, Jun Wang, Eric Lavigne, Richard Burnett, Mark Goldberg, Paul Villeneuve, Sabit Cakmak, Ray Copes
Journal: Circulation (2015)

Introduction: Experimental studies suggest that exposure to extreme ambient temperature, especially cold, can induce inflammatory reactions and a state of hypercoagulability which may in turn promote thrombosis and clot formation. However, epidemiological evidence relating cold temperature and cardiovascular-related morbidity is sparse. Even less is known about who is most susceptible to the effect of temperature. Methods: We obtained daily data on temperature and hospital admissions for any cardiovascular cause from all 14 health regions in Ontario, Canada in 1996-2013. A distributed lag non-linear model with 21 days of lag was applied to estimate the cumulative effect of temperature on selected cardiovascular conditions, controlling for air pollutants, influenza activity, relative humidity, long-term trends and day of the week. We estimated risks for cold and heat, defined as temperatures below and above the optimal temperature, which corresponded to the point with minimum cardiovascular morbidity, for each health region, and then pooled across Ontario. To identify potentially vulnerable subpopulations, we conducted stratified analyses by selected comorbidities and demographic characteristics. Results: Between 1996 and 2013, we identified 1.4 million hospitalizations from ischemic heart disease, 443,447 from myocardial infarction, 355,837 from stroke, and 237,979 from ischemic stroke across Ontario. The relationship of temperature and the selected cardiovascular conditions exhibited a U shape, with the minimum risk at ~60th percentile (12oC). For cold (at the 1st percentile temperature), the adjusted rate ratio was 1.12 (95% confidence interval (CI)=1.05-1.19) for ischemic heart disease, 1.28 (95%CI=1.13-1.44) for myocardial infarction, 1.15 (95%CI=1.02-1.30) for stroke, and 1.19 (95%CI=1.03-1.36) for ischemic stroke. Heat also exhibited elevated risks, albeit not significant, for these conditions. We found that the risk of ischemic heart disease from cold was highest among those with a history of conduction disorders, whereas the risk of stroke from cold was highest in those with arrhythmias. Conclusions: Acute exposure to cold temperature contributed to excess hospitalizations from cardiovascular disease in Ontario.
A double-reprocessing high-level disinfection protocol does not eliminate positive cultures from the elevators of duodenoscopes
Authors: Douglas Rex, Marnie Sieber, Glen Lehman, Douglas Webb, Bryan Schmitt, Amy Kressel, Ji Bang, Jeffery Easler, Lee McHenry, Ihab El-Hajj, Evan Fogel, James Watkins, Stuart Sherman
Journal: Endoscopy (2017)

Duodenoscopes have been the source of serious infection, despite correct performance of high-level disinfection (HLD). This study aimed to observe the impact of performing HLD twice on the rate of positive cultures from duodenoscope elevators.We performed double HLD (DHLD; i. e. complete manual cleaning followed by automated reprocessing, with the entire process repeated) and then randomly cultured the elevators of our duodenoscopes on about 30 % of occasions.DHLD was associated with positive elevator cultures for any microorganism in 9.4 % of cases, with a 0.8 % rate of known pathogens (627 cultures) between May 2015 and February 2016. After February 2016, and in association with changing the precleaning fluid, as well as use of a new FDA-recommended cleaning brush, the rate of positive cultures for any microorganism after DHLD was 4.8 % and 0.2 % for known pathogens (420 cultures). In a third phase, characterized by a change in personnel performing DHLD and retirement of a duodenoscope with a high rate of positive cultures, the rate of positive cultures for any microorganism was 4.9 % (783 cultures) and the rate of positive culture for known pathogens was 0.3 %. To our knowledge, no duodenoscope transmission of infection occurred during the study interval.DHLD resulted in a low rate of positive cultures for known pathogens and for organisms of low pathogenic potential, but did not eliminate these, from duodenoscope elevators. Additional improvements in HLD protocols and/or duodenoscope design are needed.
Abstract #3186: Capturing cells migrating from breast tumor microenvironment: Innovative surgical approach
Authors: Mohamed El-Shinawi, Sayed Abdelwahab, Maha Sobhy, Mohamed Nouh, Mona Mohamed, Bonnie Sloane
Journal: Cancer Research (2009)

Background: In breast cancer patients, venous drainage of the breast may contain immune cells, tumor cells undergoing dissemination and other factors derived from the tumor microenvironment. Collecting venous blood via an innovative surgical approach during modified radical mastectomy and thus before dilution in the circulation may allow us to define critical biological properties of the tumor microenvironment. Aim: The aims of the present study are to: 1) develop an innovative surgical approach to collect blood from the breast tumor microenvironment through tributaries of the axillary vein, and 2) characterize and compare immunological cells collected from the axillary vein with those in peripheral blood of breast cancer patients. Methodology: We enrolled 15 women aged 30-50 years and diagnosed with breast cancer by mammography, ultrasound and biopsy (stages II-III). All patients were treatment naive pre-operatively. During routine surgical dissection, tributaries of the axillary vein were exposed for blood withdrawal. A 20-30 ml aliquot of blood was collected from tributaries of the axillary vein in heparin tubes. In addition, a 10 ml aliquot of peripheral blood was also collected in heparin tubes. Mononuclear cells were separated by Ficoll-Hypaque density gradient centrifugation. The immuno-phenotype of the isolated mononuclear cells was assessed using flow cytometry to identify the percentage of T lymphocytes (CD3+), NK cells (CD56+) and B lymphocytes (CD19+). Results: Intra-operative blood withdrawal from tributaries of the axillary vein takes about 5-10 min. We compared the cellular phenotypes of blood collected from axillary vein tributaries and peripheral veins. Flow cytometric analysis revealed a significant increase in the percentage of T-lymphocytes (CD3+) collected from axillary tributaries as compared to peripheral blood. In contrast, statistically significant differences were not detected in the percentage of natural killer cells (CD56+) and B lymphocytes (CD19+) collected from axillary tributaries and peripheral blood. Conclusion: The present study validated using an intra-operative surgical approach to capture cells drained from the tumor microenvironment through axillary tributaries. This innovative methodology may provide biologists with valuable information about the types and properties of cells in the tumor microenvironment. Our preliminary results reveal an increase in CD3+ cells collected from axillary tributaries suggesting infiltration of T-lymphocytes with their anti-tumor activity.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3186.
Abstract 14759: Aortic Valve Surgery With and Without Concomitant Septal Myectomy - A Propensity Score Matched Comparison
Authors: Konstantin von Aspern, Christian D Etz, Josephina Haunschild, Claudia Dahlenburg, Grzegorz Hirnle, Sven Lehmann, Jens Garbade, Farhad Bakhtiary, Martin Misfeld, Friedrich W Mohr
Journal: Circulation (2016)

Introduction:  Concomitant subvalvular septal myectomy during aortic valve replacement (AVR) is an effective surgical technique for septal reduction therapy. Higher rates of complications (e.g. pacemaker implantation) have been reported, however, comparative studies adjusting for important confounders are lacking. This study investigates outcome and complications associated with concomitant myectomy in a large cohort using propensity score matching.   Patients:  A total of 2199 consecutive patients receiving isolated AVR (N=1987) or AVR + concomitant myectomy (N=212) were included (2009-2015). The majority of patients suffered from relevant aortic valve stenosis. For comparison patients with previous cardiac procedures, emergency surgery, concomitant cardiac procedures and endocarditis were excluded.   Methods:  Comparison was performed first by examining characteristics and outcome of the overall cohort as reference to previously reported data. In a second step propensity score matching was performed with concomitant myectomy as the dependent feature.   Results:  Unmatched patients with isolated AVR were younger (68 vs 71 years,P   Conclusions:  This matched comparison study reveals that concomitant myectomy in patients undergoing surgery for AVR is a safe procedure resulting in comparable hospital mortality and long-term survival. Concomitant subvalvular myectomy seems not to increase pacemaker implantation rate. Patients after isolated AVR with and without myectomy enjoy a long-term survival equivalent to their age and sex matched normal population.
Animal studies help clarify misunderstandings about neonatal imitation
Authors: Elizabeth A. Simpson, Sarah E. Maylott, Mikael Heimann, Francys Subiaul, Annika Paukner, Stephen J. Suomi, Pier F. Ferrari
Journal: Behavioral and Brain Sciences (2017)

Abstract Empirical studies are incompatible with the proposal that neonatal imitation is arousal driven or declining with age. Nonhuman primate studies reveal a functioning brain mirror system from birth, developmental continuity in imitation and later sociability, and the malleability of neonatal imitation, shaped by the early environment. A narrow focus on arousal effects and reflexes may grossly underestimate neonatal capacities.
Once-a-Week Versus Once-Every-3-Weeks Cisplatin Chemoradiation for Locally Advanced Head and Neck Cancer: A Phase III Randomized Noninferiority Trial
Authors: Vanita Noronha, Amit Joshi, Vijay Maruti Patil, Jaiprakash Agarwal, Sarbani Ghosh-Laskar, Ashwini Budrukkar, Vedang Murthy, Tejpal Gupta, Anil K. D’Cruz, Shripad Banavali, Prathamesh S. Pai, Pankaj Chaturvedi, Devendra Chaukar, Nikhil Pande, Arun Chandrasekharan, Vikas Talreja, Dilip Harindran Vallathol, Vijayalakshmi Mathrudev, Aparna Manjrekar, Kamesh Maske, Arati Sanjay Bhelekar, Kavita Nawale, Sadhana Kannan, Vikram Gota, Atanu Bhattacharjee, Shubhada Kane, Shashikant L. Juvekar, Kumar Prabhash
Journal: Journal of Clinical Oncology (2017)

Purpose Chemoradiation with cisplatin 100 mg/m 2 given once every 3 weeks is the standard of care in locally advanced head and neck squamous cell cancer (LAHNSCC). Increasingly, low-dose once-a-week cisplatin is substituted because of perceived lower toxicity and convenience. However, there is no level 1 evidence of comparable efficacy to cisplatin once every 3 weeks. Patients and Methods In this phase III randomized trial, we assessed the noninferiority of cisplatin 30 mg/m 2 given once a week compared with cisplatin 100 mg/m 2 given once every 3 weeks, both administered concurrently with curative intent radiotherapy in patients with LAHNSCC. The primary end point was locoregional control (LRC); secondary end points included toxicity, compliance, response, progression-free survival, and overall survival. Results Between 2013 and 2017, we randomly assigned 300 patients, 150 to each arm. Two hundred seventy-nine patients (93%) received chemoradiotherapy in the adjuvant setting. At a median follow-up of 22 months, the estimated cumulative 2-year LRC rate was 58.5% in the once-a-week arm and 73.1% in the once-every-3-weeks arm, leading to an absolute difference of 14.6% (95% CI, 5.7% to 23.5%); P = .014; hazard ratio (HR), 1.76 (95% CI, 1.11 to 2.79). Acute toxicities of grade 3 or higher occurred in 71.6% of patients in the once-a-week arm and in 84.6% of patients in the once-every-3-weeks arm ( P = .006). Estimated median progression-free survival in the once-a-week arm was 17.7 months (95% CI, 0.42 to 35.05 months) and in the once-every-3-weeks arm, 28.6 months (95% CI, 15.90 to 41.30 months); HR, 1.24 (95% CI, 0.89 to 1.73); P = .21. Estimated median overall survival in the once-a-week arm was 39.5 months and was not reached in the once-every-3-weeks arm (HR, 1.14 [95% CI, 0.79 to 1.65]; P = .48). Conclusion Once-every-3-weeks cisplatin at 100 mg/m 2 resulted in superior LRC, albeit with more toxicity, than did once-a-week cisplatin at 30 mg/m 2 , and should remain the preferred chemoradiotherapy regimen for LAHNSCC in the adjuvant setting.