tbuckley/cabot-search huggingface dataset:
Abstract 17969: Cardiovascular Implantable Electronic Device Longevity Estimates at Autopsy - An Unrealized Resource?: a 5 Year Review of the Johns Hopkins Post-mortem CIED Registry
Authors: Sunil K Sinha, Barbara Crain, Katie Flickinger, Hugh Calkins, Jack Rickard, Alan Cheng, Ronald Berger, Gordon Tomaselli, Joseph E Marine
Journal: Circulation (2014)

Introduction: Feasibility of post-mortem CIED (pacemaker (PPM) or defibrillator (ICD)) retrieval for reuse has recently been shown but a model for systematic post-mortem CIED acquisition remains elusive. Prior studies of CIED longevity in retrospective autopsy and funeral home &amp; crematory series have indicated a low yield of usable devices (21 - 30%). However, processes for timely interrogation and reprogramming were not in place. We undertook a registry analysis to determine estimated longevities and reuse potential upon routine CIED retrieval at autopsy. Methods: From May 19, 2009 - May 18, 2014 adult &amp; pediatric autopsy subjects at two academic institutions underwent concomitant CIED pulse generator explantation. The CIED was interrogated by an electrophysiologist, device longevity was cataloged and the device submitted to the applicable manufacturer for formal technical analysis. Results: Seventy (4.3%) of 1642 autopsies had CIEDs. All were retrieved and interrogated within a mean 18.4 ± 14.1 days. There were 30 PPMs and 40 ICDs (4 manufacturers). CIEDs had been implanted for a mean of 2.7 ± 2.4 years and 22/70 (31.4%) had been implanted &lt; 1 year prior to death. Overall, 12/70 CIEDs (17.1%) had a longevity &lt; 1 year (including 5 at elective replacement indication (ERI), 1 recalled PPM, and 1 ICD hard reset), 20/70 (28.6%) had a longevity 1 - &lt; 4 years, and 38/70 (54.3%) had longevity ≥ 4 years. This last group demonstrated a mean longevity of 7.1 ± 2.3 years. Manufacturer technical analyses helped to confirm device longevity status and functionality, identify premature battery depletion, and confirm non-reprogrammable hard reset (due to cold exposure). Conclusion: In contrast to prior studies, our registry analysis demonstrated that the majority of CIEDs retain considerable device longevity and functionality when promptly evaluated post-mortem. Such a systematic approach represents a practical model for post-mortem CIED retrieval, evaluation and potential reuse.
A small molecule inhibitor of TGFβ RI kinase potentiates VEGF dependent angiogenesis in vitro
Authors: Jonathan M. Yingling, Jianyong Shou, Xiaoling Xia, Yuefeng Chen, Lei Yan, Wayne Evans, Donald Paul, Crystal Banks, Robert Foreman, Robin Goode, Kevin Law, Sheng-Bin Peng, Mark Uhlik, James Starling
Journal: Cancer Research (2006)

250  TGFβ, a cytokine known to regulate a wide variety of biological processes, plays important roles in regulating the tumor microenvironment and angiogenesis. TGFβ is over expressed and correlates with poor prognosis in multiple tumor types. Therapeutic modulation of TGFβ signaling has demonstrated anti-tumor activity in preclinical tumor models. However, the molecular mechanism whereby TGFβ signaling is linked to angiogenesis regulation is not well understood. We set out to test the roles of TGFβ signaling in angiogenesis by using a potent, selective TGFβ type I receptor small molecule inhibitor, LY2157299. TGFβ induced Smad2 phosphorylation in HUVEC cells in an autocrine manner. This phosphorylation event was abolished by treating the cells with LY2157299. LY2157299 also showed dose dependent potentiation of VEGF or bFGF induced cell proliferation in HUVEC. LY2157299 also promoted VEGF induced HUVEC cell migration. To further evaluate TGFβ signaling in angiogenesis, we assayed TGFβ and LY2157299 in an optimized in vitro angiogenesis co-culture model, in which HUVEC cells form cord structures on dermal fibroblast feeder layers. Cord formation was captured and quantitated by using high content ArrayScan imaging analysis.. TGFβ was found to inhibit cord formation in a dose-dependent fashion. This inhibition was neutralized by addition of a pan-TGFβ neutralizing antibody. Interestingly,, LY2157299, but not a control compound, potentiated angiogenesis in the VEGF-stimulated cord formation assay. High density microarray transcript profiling studies are in progress to elucidate the mechanism of angiogenic potentiation by LY2157299 in the in vitro cord formation assay. In vivo evaluation of P-Smad2 inhibition in xenograft and orthotopic tumors led to the optimization of the dose and schedule for pre-clinical efficacy studies and subsequent evaluation of the angiogenic effects of LY2157299. Although anti-tumor activity has been observed in several pre-clinical models, LY2157299 failed to show significant in vivo angiogenic effects in the 4T1, Colo205, or A549 xenograft models.
Values of Neutral Endopeptidase 24.11 As a Tubular Marker in Human Renal Interstitial Fibrosis With Tubular Atrophy
Authors: J. Nortier, S. Simon, N. Thielemans, E. Deprez, M. Depierreux, C. Richard, Alfred Bernard, Robert Lauwerys, M. Deschodtlanckman, Jl. Vanherweghem
Journal: Journal of the American Society of Nephrology (1994)
Differential ERK activation during autophagy induced by europium hydroxide nanorods and trehalose: Maximum clearance of huntingtin aggregates through combined treatment
Authors: Peng-Fei Wei, Pei-Pei Jin, Ayan Kumar Barui, Yi Hu, Li Zhang, Ji-Qian Zhang, Shan-Shan Shi, Hou-Rui Zhang, Jun Lin, Wei Zhou, Yun-Jiao Zhang, Ren-Quan Ruan, Chitta Ranjan Patra, Long-Ping Wen
Journal: Biomaterials (2015)
SL-401, A Novel Targeted Therapy Directed To The Interleukin-3 Receptor (IL-3R), Inhibits Plasmacytoid Dendritic Cell (pDC)-Induced Myeloma Cell Growth and Overcomes Drug Resistance
Authors: Arghya Ray, Deepika Sharma Das, Ze Tian, Vincent Macri, Christopher L. Brooks, Paul G. Richardson, Eric Rowinsky, Dharminder Chauhan, Kenneth C. Anderson
Journal: Blood (2013)
Hypoxia-induced p53 modulates both apoptosis and radiosensitivity via AKT
Authors: Katarzyna B. Leszczynska, Iosifina P. Foskolou, Aswin G. Abraham, Selvakumar Anbalagan, Céline Tellier, Syed Haider, Paul N. Span, Eric E. O’Neill, Francesca M. Buffa, Ester M. Hammond
Journal: Journal of Clinical Investigation (2015)

Restoration of hypoxia-induced apoptosis in tumors harboring p53 mutations has been proposed as a potential therapeutic strategy; however, the transcriptional targets that mediate hypoxia-induced p53-dependent apoptosis remain elusive. Here, we demonstrated that hypoxia-induced p53-dependent apoptosis is reliant on the DNA-binding and transactivation domains of p53 but not on the acetylation sites K120 and K164, which, in contrast, are essential for DNA damage-induced, p53-dependent apoptosis. Evaluation of hypoxia-induced transcripts in multiple cell lines identified a group of genes that are hypoxia-inducible proapoptotic targets of p53, including inositol polyphosphate-5-phosphatase (INPP5D), pleckstrin domain-containing A3 (PHLDA3), sulfatase 2 (SULF2), B cell translocation gene 2 (BTG2), cytoplasmic FMR1-interacting protein 2 (CYFIP2), and KN motif and ankyrin repeat domains 3 (KANK3). These targets were also regulated by p53 in human cancers, including breast, brain, colorectal, kidney, bladder, and melanoma cancers. Downregulation of these hypoxia-inducible targets associated with poor prognosis, suggesting that hypoxia-induced apoptosis contributes to p53-mediated tumor suppression and treatment response. Induction of p53 targets, PHLDA3, and a specific INPP5D transcript mediated apoptosis in response to hypoxia through AKT inhibition. Moreover, pharmacological inhibition of AKT led to apoptosis in the hypoxic regions of p53-deficient tumors and consequently increased radiosensitivity. Together, these results identify mediators of hypoxia-induced p53-dependent apoptosis and suggest AKT inhibition may improve radiotherapy response in p53-deficient tumors.
Abstract 4648: Mechanism of Tissue Cooling With Cryoenergy Delivery to Pulmonary Veins: Tissue Temperature Distribution and Chonic Esophageal Effects
Authors: Charles Dalegrave, Benhur D Henz, Yasuo Okumura, Mark Kolasa, Dylan V Miller, Susan B Johnson, Douglas L Packer
Journal: Circulation (2008)

Background: Although pulmonary vein (PV) isolation has been used to treat AF, complications create important limitations. New energy sources, including cryothermal, have been developed to minimize these complications. The purpose of this study was to evaluate the effect of PV cryoablation on esophageal (ESO) temperatures acutely and correlate them with chronic effects on the esophageal wall. Methods: A 23 mm cryoballoon was placed in the LA of 10 dogs through a 12 Fr deflectable sheath. PV and ESO temperatures (TEMP) were recorded using 7–9 thermocouples (TC) outside the PVs and on the external and internal ESO surfaces during 2 cryoablations of 4 min duration. Results : Cryoablation of 15 PV (10 RIPV and 5 LIPV) during 1.7±0.6 ablations yielded a total of 168 TC time-TEMP profiles (6.4±2.4/PV). Minimum tissue TEMP was inversely dependent on the distance of the TC from the balloon surface (Table 1 ). All PVs were isolated acutely and 14/15 (93%) chronically. Minimum TEMP achieved at the PV surface and external ESO were similar (−32±8 and −37±9 at targets within 2.5 mm from the balloon respectively [P=NS]). A TEMP decrease at the internal ESO was seen during 15 of 25 (60%) ablations, but was significantly less pronounced than the external TEMP (17.9°C±13.3 and 6.1°C±24.8 [p&lt;0.05]) resulting in a minimum recorded internal TEMP of −6.2°C. The ESO histological examination in 5 dogs showed very limited external lesions in these dogs (depth= 2.2±1.1, width3 18.6±7.4 and length= 12±5.7 mm), but no transmural or internal ulceration, fibrosis or scarring seen. Conclusion: Although PV cryoablation decreases external ESO temperature and produces minor lesions, significant chronic disruptive tissue damage was not seen. Esophageal injury is an unlikely, but potential complication of cryoablation, with internal temperature proving unhelpful in predict negative outcome.
B-Type Natriuretic Peptide and the Effect of Ranolazine in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes
Authors: David A. Morrow, Benjamin M. Scirica, Marc S. Sabatine, James A. de Lemos, Sabina A. Murphy, Petr Jarolim, Pierre Theroux, Christophe Bode, Eugene Braunwald
Journal: Journal of the American College of Cardiology (2010)
Abstract 12906: Impact of Blood Pressure Control in Type 2 Diabetes Patients in Relation to Aspirin Therapy: Insight From the JPAD Trial
Authors: Hirofumi Soejima, Masafumi Nakayama, Takeshi Morimoto, Mio Sakuma, Shiro Uemura, Masao Kanauchi, Naofumi Doi, Hideaki Jinnouchi, Seigo Sugiyama, Masako Waki, Sadanori Okada, Takahiro Kawano, Yoshihiko Saito, Hisao Ogawa
Journal: Circulation (2010)

Background: The Japanese primary prevention of atherosclerosis with aspirin for diabetes (JPAD) trial was undertaken to examine the efficacy of aspirin therapy. Multicenter, prospective, randomized, open label, blinded, end-point trial conducted from 2002 through 2008, which enrolled 2539 patients and had a median follow-up of 4.37 years. Methods: In the subgroup analysis of the JPAD trial, we divided the patients into uncontrolled blood pressure (BP) group (systolic BP≥140 mmHg or diastolic BP≥90 mmHg or both) or controlled BP group according to baseline BP. We also divided the patients into uncontrolled BP group (systolic BP≥130 mmHg or diastolic BP≥80 mmHg or both) or controlled BP group. We examined whether there was any difference in the effect of aspirin therapy according to the level of BP control. Results: When the JPAD patients were divided into two groups by BP 140/90 mmHg, the incidence of stroke events was significantly higher in the uncontrolled BP group than in the controlled BP group (hazar...
Food Sources of Protein and Risk of Incident Gout in the Singapore Chinese Health Study
Authors: Gim Gee Teng, An Pan, Jian‐Min Yuan, Woon‐Puay Koh
Journal: Arthritis & Rheumatology (2015)

Objective Prospective studies evaluating diet in relation to the risk of gout in Asian populations are lacking. The purpose of this study was to examine the relationship between the consumption of dietary protein from each of its major sources and the risk of gout in a Chinese population. Methods We used data from the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese adults who were 45–74 years old at recruitment during the years 1993–1998. Habitual diet information was collected via a validated semiquantitative food frequency questionnaire, and physician‐diagnosed gout was self‐reported during 2 followup interviews up to the year 2010. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs), with adjustment for potential confounders, among 51,114 eligible study participants who were free of gout at baseline and responded to our followup interviews. Results A total of 2,167 participants reported physician‐diagnosed gout during the followup period. The multivariate‐adjusted HRs (with 95% CIs) of gout, comparing the first quartile with the fourth quartile, were as follows: 1.27 (1.12–1.44; P for trend &lt; 0.001) for total protein, 1.27 (1.11–1.45; P for trend &lt; 0.001) for poultry, 1.16 (1.02–1.32; P for trend = 0.006) for fish and shellfish, 0.86 (0.75–0.98; P for trend = 0.018) for soy food, and 0.83 (0.73–0.95; P for trend = 0.012) for nonsoy legumes. No statistically significant associations were found with protein intake from other sources (red meat, eggs, dairy products, grains, or nuts and seeds). Conclusion In this Chinese population living in Singapore, higher total dietary protein intake from mainly poultry and fish/shellfish was associated with an increased risk of gout, while dietary intake of soy and nonsoy legumes was associated with a reduced risk of gout.
What caused the 1918–30 Epidemic of Encephalitis Lethargica?
Authors: R R Dourmashkin
Journal: Journal of the Royal Society of Medicine (1997)

Encephalitis lethargica, often called epidemic encephalitis at the time of the epidemic, was prevalent worldwide during the years 1918-1930. The acute phase, characterized by somnolence and a mask-like facial appearance, was associated with a 20-40% mortality. Later in the epidemic, almost all those who had had an acute episode of encephalitis lethargica developed sequelae to a greater or lesser degree. In some cases, the symptoms persisted without respite to the chronic state; in others they developed weeks, months or years after the patient was thought to have recovered. The outstanding motor manifestation was the parkinsonian syndrome, present in almost every case. This resembled the picture of Parkinson's disease (paralysis agitans), except that the 'pill-rolling' movement typical of Parkinson's disease was often absent; the tremor in postencephalitic parkinsonism was usually coarse. The common general features of the latter were rigidity of all the muscles, loss of automatic or synergistic movements, loss of equilibrium, and a running or shuffling gait. Oculogyric crises were an important feature. There were mental changes, especially in children, and respiratory tics were often noted2. Sometimes signs of pyramidal tract damage were found3.
The efficacy and safety of the Dorzolamide—timolol combination versus the concomitant administration of its components11Ms. Strohmaier and Drs. Snyder and Adamsons are employees of Merck &amp; Co., Inc, the manufacturer of the dorzolamide-timolol combination. Dr. DuBiner has no proprietary interest in the dorzolamide-timolol combination or Merck.
Authors: Kim Strohmaier, Ellen Snyder, Harvey DuBiner, Ingrid Adamsons
Journal: Ophthalmology (1998)
Perioperative Use of β-Blockers in Cardiac and Noncardiac Surgery
Authors: Hermann Blessberger, Juergen Kammler, Clemens Steinwender
Journal: JAMA (2015)

<h3>Clinical Question</h3> Are β-blockers associated with lower rates of mortality and morbidity after cardiac or noncardiac surgery? <h3>Bottom Line</h3> In cardiac surgery, β-blockers are associated with a lower incidence of supraventricular tachycardias (SVTs) and ventricular arrhythmias. In noncardiac surgery, β-blockers are associated with a possible increase in mortality and strokes, a lower incidence of acute myocardial infarctions (AMIs) and SVTs, and an increase in bradycardia and hypotension. If tolerated, long-term β-blocker treatment should be continued perioperatively, whereas the decision to start a β-blocker should be individualized, weighing risks and benefits.
MLN4924, a Novel Investigational Inhibitor Of NEDD8-Activating Enzyme (NAE), In Adult Patients With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS): Results From Multiple Dosing Schedules In a Phase 1 Study
Authors: Daniel J. DeAngelo, Harry P Erba, Michael B Maris, Ronan T. Swords, Faiz Anwer, Jessica K Altman, Zhaowei Hua, Stephen J Blakemore, Hélène Faessel, Bruce J Dezube, Bruno C Medeiros
Journal: Blood (2013)
Abstract 16458: Micro RNA 221 and 222: An miRNA Cassette With Opposing Effects on Angiogenesis
Authors: Alexis Cunningham, Tao Wang, R. John Lye, Brian Annex
Journal: Circulation (2014)

Background: Micro RNAs (miRs) are small non-coding RNAs that regulate gene expression by degradation of mRNAs or inhibition of protein translation. Many miRs are co-expressed and co-regulated and some miRs have been shown to positively and negatively affect angiogenesis. Here we report that miR-221 and 222 are co-expressed but have completely opposite effects on angiogenesis. Methods and Results: The expression of miR221 and miR222 were detected in human plasma and in cell culture using real-time qPCR with available primer-probe sets. Both miRs showed higher expression (miR221: 4 fold, p=0.03; miR222: 1.4 fold, p=0.05) in a subset of patients with the most severe form of peripheral arterial disease (PAD) when compared to other PAD patients. The forced overexpression in human endothelial cells with miR-221 mimic results in an increase in cell proliferation, increase cell viability and forms more tube like structures on matrigel assay under hypoxic serum starvation (HSS) compared to the negative control (p<...
Abstract 464: Hypoxia-induced miR-210 potentiates MDSC function through regulation of Arg1, Il-16 and Cxcl12, and promotes tumor growth
Authors: Muhammad Zaeem Noman, Salem Chouaib
Journal: Cancer Research (2015)

Abstract Myeloid Derived Suppressor Cells (MDSCs) are an integral component of the hypoxic tumor microenvironment. We demonstrated that hypoxia selectively induced miR-210 via HIF-1α in splenic MDSCs from tumor-bearing mice. Overexpression of miR-210 enhanced MDSC-mediated T cell suppression under normoxia, while targeting of hypoxic miR-210 decreased MDSC function. Our data show that miR-210 modulated MDSCs function by increasing arginase activity and NO production, although it had no effect on ROS or cytokine (IL-6 and IL-10) production and PD-L1 expression. A comprehensive approach using microRNA target predictions tool, transcriptome analysis, and luciferase reporter assay strongly pointed to the regulation of Arg1, Cxcl12 and Il16 at both mRNA and protein levels by miR-210 in splenic MDSCs. In mediating the immunosuppressive effects of miR-210, targeting of Arg1, and blockade of IL-16 and CXCL12, in splenic MDSCs from tumor-bearing mice under normoxia dramatically decreased MDSC-mediated T cell proliferative response and IFN-gamma production. Interestingly, miR-210 overexpressing MDSCs enhanced in vivo their immune suppressive activity resulting in an increase in 4T1 tumor growth. Therefore, the potential therapeutic use of miR-210 inhibitor oligonucleotide alone, or along with HIF-1α inhibitors as adjuvant tool combined to immunotherapeutic approaches, may be beneficial for boosting the immune system in cancer patients. Citation Format: Muhammad Zaeem Noman, Salem Chouaib. Hypoxia-induced miR-210 potentiates MDSC function through regulation of Arg1, Il-16 and Cxcl12, and promotes tumor growth. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 464. doi:10.1158/1538-7445.AM2015-464
Abstract 13139: In Vivo Differentiation of Epigenetically Reprogrammed Mouse and Human Endothelial Progenitor Cells into Cardiomyocytes Enhances Functional and Anatomical Post-Infarct Myocardial Repair
Authors: Melissa A Thal, Prasanna Krishnamurthy, Eneda Hoxha, Erin Lambers, Suresh Verma, Gangjian Qin, Douglas Losordo, Raj Kishore
Journal: Circulation (2011)

Melissa A Thal, 2011 Finalist and Presenting Author
Complicationsarising from endobronchial ultrasound (EBUS): Impact of trainee participation
Authors: Kiran Sharma, Shera Tan, Kah Yeee Tham, Aik Hau Tan, Therese Sophie Lapperre Stevens, Chian Min Loo, Mariko Koh
Journal: European Respiratory Journal (2014)

Background:  Despite the widespread use of EBUS -Transbronchial needle aspiration (TBNA), the reported complication incidence is relatively low. This could be due to under-reporting.   Aim:  To assess the complication rate (patient adverse events and scope damages) of performing EBUS-TBNA and the impact of trainee participation on complication rate.   Methods:  Retrospective analysis of all consecutive EBUS-TBNA performed in at Singapore General Hospital between 2008 and 2013. Reported complications were classified into major or minor events. Damages to scopes and cost of repair were also recorded. The impact of trainee participation was analysed.   Results:  597 EBUS-TBNA procedures were performed. 39 complications occurred during performance of EBUS-TBNA; 2 major and 37 minor. One patient died within 24 hours of EBUS-TBNA; attributed to acute myocardial infarction. One patient had superior vena cava obstruction and had severe contact bleeding prior to TBNA requiring intubation. Rest of EBUS complications were minor. Trainees were involved in 71.7% (28/39) of EBUS-TBNA with complications, but complication rates have reduced from 20.8% in 2011 to 14.86% in 2013. During this period, the EBUS scope was damaged 7 times requiring S$55,740 (€32,325) for repair.The frequency of EBUS scope damage has reduced from 3 times in 2012 to none in 2013. Scope damages related to trainee participation was 85% (6/7).   Conclusions:  Complication rates and number of scope damages were higher with trainee participation. However, with better training and more experience these complications can be reduced.