tbuckley/cabot-search huggingface dataset:
Abstract 178: Evaluating Effects of Lysophosphatidic Acid on Neurological Function in a Rodent Model of Cardiac Arrest
Authors: Mitsuaki Nishikimi, Tsukasa Yagi, Muhammad Shoaib, Yu Okuma, Tai Yin, Lance B Becker, Junhwan Kim
Journal: Circulation (2019)

Introduction: Lysophosphatidic acid (LPA) has been shown to increase blood brain barrier permeability for a short periods of time, which may be utilized as a potential drug delivery mechanism to the brain in cardiac arrest. In addition, prior studies have suggested a potential neuroprotective role of LPA administration. However, no study has investigated the effects of LPA in cardiac arrest. Objective: The aim of this study is to evaluate the effects of intravenously administered LPA on neurological function and survival outcomes of rats after cardiac arrest. Methods: Adult maleSprague-Dawley rats were subjected to 8 min of asphyxial cardiac arrestand resuscitated using chest compressions. After achieving return of spontaneous circulation (ROSC), rats were treated with either LPA or vehicle. Survival was followed for up to 24 hours after cardiac arrest. For all surviving rats, neurological outcome was examined using a modified Neurological Deficit Score (mNDS) in a blinded manner. Results: Baseline characteristics, including body weight, surgical procedure time, vital signs before cardiac arrest, cardiac arrest duration, chest compression time, and time to achieve ROSC were similar between LPA-treated (n = 8) and vehicle-treated (n = 11) groups. There was no statistically significant difference in 24 hour survival between the two groups (LPA, 75.0% (6/8) vs. vehicle, 45.5% (5/11), p = 0.15). However, LPA-treated rats exhibited significantly improved neurological function at 24 hours examination (LPA, 89.3% ± 5.0 vs. vehicle, 75.6% ± 7.1, p = 0.01). This difference was most apparent in retention of coordination ability in the LPA group (LPA, 66.7% ± 18.6 vs vehicle, 20% ± 18.7, p &lt; 0.01) Conclusion: LPA administration in post-cardiac arrest rats significantly improved neurological function at 24 hours after cardiac arrest. LPA has a potential to serve as a novel therapeutic in cardiac arrest.
Pharmacokinetics, Safety, and Antitumor Effect of Apalutamide with Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer: Phase Ib Study
Authors: Edwin M. Posadas, Kim N. Chi, Ronald de Wit, Maja J.A. de Jonge, Gerhardt Attard, Terence W. Friedlander, Margaret K. Yu, Peter Hellemans, Caly Chien, Charlene Abrams, Juhui J. Jiao, Fred Saad
Journal: Clinical Cancer Research (2020)

Apalutamide is a next-generation androgen receptor (AR) inhibitor approved for patients with nonmetastatic castration-resistant prostate cancer (CRPC) and metastatic castration-sensitive prostate cancer. We evaluated the pharmacokinetics, safety, and antitumor activity of apalutamide combined with abiraterone acetate plus prednisone (AA-P) in patients with metastatic CRPC (mCRPC).
Abstract 15131: Early Withdrawal of Life-Sustaining Therapy for Perceived Neurological Prognosis is Associated With Excess Mortality After Out-of-Hospital Cardiac Arrest
Authors: Jonathan Elmer, Cesar Torres, Tom P Aufderheide, Michael A Austin, Clifton W Callaway, Eyal Golan, Heather Herren, Jamie Jasti, Peter J Kudenchuk, Damon C Scales, Dion Stub, Derek K Richardson, Dana M Zive
Journal: Circulation (2015)

Introduction: Withdrawal of life-sustaining therapy because of perceived poor neurological prognosis (WLST-N) is a common cause of death after out-of-hospital cardiac arrest. Guidelines recommend against WLST-N before 72 h (WLST-N&lt;72), but WLST-N&lt;72 remains common and may increase mortality. Methods: We performed a secondary analysis of the Resuscitation Outcomes Consortium’s PRIMED trial including adults surviving &gt;1h after hospital arrival. Our main exposure was WLST-N&lt;72, which was collected for the original trial by chart review. Outcomes were survival to hospital discharge and functionally favorable survival (modified Rankin Score ≤ 3). We used two methods to determine predicted outcomes in the cohort exposed to WLST-N&lt;72 if WLST-N were delayed until after 72h. First, we used pre-exposure covariates to create a propensity score modeling the probability of exposure to WLST-N&lt;72 and propensity-matched exposed to unexposed subjects, treating subjects with WLST-N after 72h as unexposed. We then determined the probability of survival and functionally favorable survival in the unexposed matched cohort. Second, we fit adjusted logistic regression models using data from the unexposed cohort and used these models to predict outcomes in the exposed cohort. Results: Of 16,875 OHCA subjects, 4,265 (25%) met inclusion criteria. Of these, 1,490 (35%) survived to discharge and 1101 (26%) had a functionally favorable survival. WLST-N occurred in 1626 (59% of non-survivors), most commonly on hospital day 1, and 919 (33% of non-survivors) were exposed to WLST-N&lt;72. After matching, there were no differences between the exposed and unexposed groups. In adjusted analyses, exposed subjects had an estimated 25-26% chance of survival and 16% functionally favorable survival had they not received WLST-N&lt;72. Conclusion: In this large North American cohort, death associated with WLST-N&lt;72 was common. Extrapolating to national epidemiological data, our findings indicate that approximately 4,500 Americans annually who would otherwise survive to discharge instead die because of WLST-N&lt;72, nearly 2,900 (64%) of whom might have had functional recovery. Reducing WLST-N&lt;72 may be an important means to decrease mortality after OHCA and improve public health.
Oral nitrate supplementation to enhance pulmonary rehabilitation in COPD: ON-EPIC a multicentre, double-blind, placebo-controlled, randomised parallel group study
Authors: Matthew J Pavitt, Rebecca Jayne Tanner, Adam Lewis, Sara Buttery, Bhavin Mehta, Helen Jefford, Katrina J Curtis, Winston A S Banya, Syed Husain, Karnan Satkunam, Dinesh Shrikrishna, William Man, Michael I Polkey, Nicholas S Hopkinson
Journal: Thorax (2020)

Rationale Dietary nitrate supplementation has been proposed as a strategy to improve exercise performance, both in healthy individuals and in people with COPD. We aimed to assess whether it could enhance the effect of pulmonary rehabilitation (PR) in COPD. Methods This double-blind, placebo-controlled, parallel group, randomised controlled study performed at four UK centres, enrolled adults with Global Initiative for Chronic Obstructive Lung Disease grade II–IV COPD and Medical Research Council dyspnoea score 3–5 or functional limitation to undertake a twice weekly 8-week PR programme. They were randomly assigned (1:1) to either 140 mL of nitrate-rich beetroot juice (BRJ) (12.9 mmol nitrate), or placebo nitrate-deplete BRJ, consumed 3 hours prior to undertaking each PR session. Allocation used computer-generated block randomisation. Measurements The primary outcome was change in incremental shuttle walk test (ISWT) distance. Secondary outcomes included quality of life, physical activity level, endothelial function via flow-mediated dilatation, fat-free mass index and blood pressure parameters. Results 165 participants were recruited, 78 randomised to nitrate-rich BRJ and 87 randomised to placebo. Exercise capacity increased more with active treatment (n=57) than placebo (n=65); median (IQR) change in ISWT distance +60 m (10, 85) vs +30 m (0, 70), estimated treatment effect 30 m (95% CI 10 to 40); p=0.027. Active treatment also impacted on systolic blood pressure: treatment group −5.0 mm Hg (−5.0, –3.0) versus control +6.0 mm Hg (−1.0, 15.5), estimated treatment effect −7 mm Hg (95% CI 7 to −20) (p&lt;0.0005). No significant serious adverse events or side effects were reported. Conclusions Dietary nitrate supplementation appears to be a well-tolerated and effective strategy to augment the benefits of PR in COPD. Trial registration number ISRCTN27860457 .
1082. Delivery of Anti-Oxidative Enzyme Genes Protects Against Ischemia/Reperfusion-Induced Liver Injury in Mice
Authors: Song-Qing He, Yan-Hong Zhang, Senthil K. Venugopal, Christopher W. Dicus, Richard V. Perez, Mark A. Zern, Michael H. Nantz, Jian Wu
Journal: Molecular Therapy (2006)

BACKGROUND: Hepatic ischemic/reperfusion (I/R) injury is characterized by the generation of reactive oxygen species (ROS), such as superoxide anions and hydrogen peroxide. The aim of this study is to investigate whether anti-oxidative gene delivery by our polycationic liposomes will be an effective approach for prevention of the injury. METHODS: Polycationic liposome-mediated extracellular superoxide dismutase (EC-SOD) or/and catalase gene delivery by portal vein injection was undertaken one day prior to warm I/R injury in mice. The effects of the gene delivery were determined 6 hours after starting reperfusion. RESULTS: Polycationic liposome-mediated anti-oxidative gene delivery led to marked hepatic transgene expression. There was a 56-fold increase in human EC-SOD gene expression in the liver 30 hours after injection of EC-SOD lipoplexes as shown by real time RT-PCR; Western blot analysis demonstrated a 10-fold increase in catalase protein levels in the liver as compared to controls. Liver SOD and catalase activity increased 16.6-fold and 9-fold, respectively. The overexpression of these two anti-oxidative genes significantly suppressed the subsequent I/R-induced acute liver injury as reflected by markedreduction of serum ALT levels (520±55 and 643±24 vs. 1217±193 units/ml, p<0.01). The I/R procedure significantly increased liver superoxide anions (699±83 vs. 20±13 RLU/sec/mg, p<0.01) as detected by a chemoluminescent method with a superoxide tracer, MCLA. These levels were markedly reduced to a nearly normal level (24±7 RLU/sec/mg) by the prior delivery of the EC-SOD gene. In addition, there were reduced liver malondialdehyde levels, and restored glutathione levels, in mice receiving either EC-SOD or catalase gene delivery. Moreover, the enhanced activation of nuclear factor-κB and AP-1 in hepatic I/R injury was minimized by the anti-oxidative gene delivery. The control lipoplexes did not affect the extent of liver injury and oxidant stress levels in this I/R model. The combination of EC-SOD and catalase lipoplex injection (in half amount of each plasmid) resulted in a slight improvement in hepatic I/R injury when compared to either alone. CONCLUSIONS: The findings demonstrate that polycationic liposome-mediated EC-SOD or catalase gene delivery led to high levels of the transgene activity in the liver, and markedly attenuated liver I/R injury. The protection is associated with enhanced anti-oxidative effects in the liver. To our knowledge, this is the first successful demonstration that polycationic liposome-mediated EC-SOD and/or catalase gene delivery ameliorates warm I/R-associated liver injury in mice. This approach may become a potential novel therapy to improve graft function and survival after liver transplantation.
Overlap Weighting
Authors: Laine E. Thomas, Fan Li, Michael J. Pencina
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Non-canonical signaling pathway of SNAI2 induces EMT in ovarian cancer cells by suppressing miR-222-3p transcription and upregulating PDCD10
Authors: Lili Fan, Han Lei, Sai Zhang, Yulong Peng, Chunyan Fu, Guang Shu, Gang Yin
Journal: Theranostics (2020)

: Epithelial ovarian cancer (EOC) is one of the most lethal malignancies in women worldwide. Many studies showed the transcription factor SNAI2-induced Epithelial-Mesenchymal Transition (EMT) through inhibiting E-cadherin (E-cad) expression. Our previous study reported that miR-222-3p was an important tumor-suppressive miRNA for EOC development and dissemination. The present study aimed to acquire a deeper mechanistic understanding of the role of miR-222-3p regulation that might contribute to improving current anti-metastasis strategies in EOC.
RISK OF RECURRENT CARDIAC EVENTS AFTER ONSET OF MENOPAUSE IN WOMEN WITH LONG QT SYNDROME TYPES 1 AND 2
Authors: Yonatan Buber, Mathew Jehu, Arthur J. Moss, Alon Barsheshet, Scott McNitt, Wojciech Zareba, Michael J. Ackerman, Michael Eldar, Elizabeth S. Kaufman, David Luria, Jeffrey A. Towbin, Michael Vincent, Ilan Goldenberg
Journal: Journal of the American College of Cardiology (2011)
Sialic acid-modified chitosan oligosaccharide-based biphasic calcium phosphate promote synergetic bone formation in rheumatoid arthritis therapy
Authors: Xiao-Ling Xu, Gao-Feng Shu, Xiao-Juan Wang, Jing Qi, Fei-Yang Jin, Qi-Ying Shen, Xiao-Ying Ying, Jian-Song Ji, Yong-Zhong Du
Journal: Journal of Controlled Release (2020)
Synthesis of micellar-like terpolymer nanoparticles with reductively-cleavable cross-links and evaluation of efficacy in 2D and 3D models of triple negative breast cancer
Authors: Patrícia F. Monteiro, Muhammad Gulfam, Cíntia J. Monteiro, Alessandra Travanut, Thais Fedatto Abelha, Amanda K. Pearce, Christine Jerôme, Anna M. Grabowska, Philip A. Clarke, Hilary M. Collins, David M. Heery, Pavel Gershkovich, Cameron Alexander
Journal: Journal of Controlled Release (2020)
SUMO1 modification of methyltransferase-like 3 promotes tumor progression via regulating Snail mRNA homeostasis in hepatocellular carcinoma
Authors: Hongfa Xu, Hao Wang, Wei Zhao, Sirui Fu, Yong Li, Wenjun Ni, Yongjie Xin, Wei Li, Chenzi Yang, Yanyan Bai, Meixiao Zhan, Ligong Lu
Journal: Theranostics (2020)

Rationale: Hepatocellular carcinoma (HCC) is one of the leading causes of mortality worldwide. Methyltransferase-like 3 (Mettl3), an RNA N6-methyladenosine (m6A) methyltransferase, has been shown to act as an oncogene in several human cancers. However, the regulatory role of posttranslational modifications of Mettl3 in liver cancer remains elusive. Methods: SUMOylation was analyzed using immunoprecipitation and western blot assays. In vitro and in vivo biological functions were examined using MTS, colony formation, wound healing, transwell, apoptosis, and viability assays and the BALB/c nude mouse model, respectively. Immunohistochemistry was conducted to evaluate the prognostic value of Mettl3 expression in HCC. The regulatory mechanism of Mettl3 in HCC was investigated by m6A dot blot, immunofluorescence, dual luciferase reporter, protein stability, and RNA stability assays. Results: Mettl3 was found to be SUMOylated by a small ubiquitin-like modifier SUMO1. Further, SUMOylation of Mettl3 was increased upon mitogen stimulation, which correlated with UBC9 upregulation, and was positively correlated with high metastatic potential of liver cancer. Finally, SUMOylation of Mettl3 was found to regulate HCC progression via controlling Snail mRNA homeostasis in an m6A methyltransferase activity-dependent manner. Conclusions: This study revealed a novel mechanism of SUMOylated Mettl3-mediated Snail mRNA homeostasis, identifying the UBC9/SUMOylated Mettl3/Snail axis as a novel mediator of the SUMO pathway involved in HCC progression.
Abstract 108: The Change and Effect of Dispatcher Telephone Instructions for Cardiopulmonary Resuscitation with Chest Compressions Only
Authors: Ken Nagao, Eizo Tachibana, Kei Nishikawa, Tsukasa Yagi, Naohiro Yonemoto, Morimasa Takayama, Hiroshi Nonogi, Shinichi Shirai, Takeshi Kimura, Asuka Kasai
Journal: Circulation (2012)

BACKGROUND The 2010 AHA guidelines for CPR recommended that dispatchers should instruct untrained lay rescuers to provide chest compression-only CPR for adults with out-of-hospital cardiac arrest. ...
From the micro to the macro to improve health: microorganism ecology and society in teaching infectious disease epidemiology
Authors: Maryam Shahmanesh, Guy Harling, Cordelia E M Coltart, Heather Bailey, Carina King, Jo Gibbs, Janet Seeley, Andrew Phillips, Caroline A Sabin, Robert W Aldridge, Pam Sonnenberg, Graham Hart, Mike Rowson, Deenan Pillay, Anne M Johnson, Ibrahim Abubakar, Nigel Field
Journal: The Lancet Infectious Diseases (2020)

Chronic and emerging infectious diseases and antimicrobial resistance remain a substantial global health threat. Microbiota are increasingly recognised to play an important role in health. Infections also have a profound effect beyond health, especially on global and local economies. To maximise health improvements, the field of infectious disease epidemiology needs to derive learning from ecology and traditional epidemiology. New methodologies and tools are transforming understanding of these systems, from a better understanding of socioeconomic, environmental, and cultural drivers of infection, to improved methods to detect microorganisms, describe the immunome, and understand the role of human microbiota. However, exploiting the potential of novel methods to improve global health remains elusive. We argue that to exploit these advances a shift is required in the teaching of infectious disease epidemiology to ensure that students are well versed in a breadth of disciplines, while maintaining core epidemiological skills. We discuss the following key points using a series of teaching vignettes: (1) integrated training in classic and novel techniques is needed to develop future scientists and professionals who can work from the micro (interactions between pathogens, their cohabiting microbiota, and the host at a molecular and cellular level), with the meso (the affected communities), and to the macro (wider contextual drivers of disease); (2) teach students to use a team-science multidisciplinary approach to effectively integrate biological, clinical, epidemiological, and social tools into public health; and (3) develop the intellectual skills to critically engage with emerging technologies and resolve evolving ethical dilemmas. Finally, students should appreciate that the voices of communities affected by infection need to be kept at the heart of their work.
PTH-059 Analysis of 140000 patients with bile duct stones presenting to english acute trusts, 2013–2016
Authors: Maxime Delvincourt, Jodi Carter, Keith Bodger, George Webster, Richard Sturgess
Journal: Endoscopy (2018)

Common ile uct (CBD) stones 10%–20% of patients with gallstone disease. ndoscopic retrograde cholangio-pancreatography (ERCP) <h3>Methods</h3> All adult patients with diagnosis (ICD-10) codes for alculus of bile duct with cholangitisalculus of bile duct with cholecystitisalculusofbile duct without cholangitis were used to select results from HospitalEpisode Statistics (HES) data for the years 2013/14 – 2016/17. Episodes were excluded where there were episodes with one or moreof these codes for the previous 2 financial years to censor patients already on a CBD pathway. <h3>Results</h3> There were 1 40 890 patients identified, of which 91 178 (64.72%) were female Mean age at first admission was 70. Of the 1 40 890 individual patients, 1 02 072 (72%) had an emergency first admission. The incidence of cases in each year was 33,557, 35,053, 35 621 and 36 659 respectively. were performed on 48 306 patients in this cohort over the study period Of the 48 306 individuals who had an ERCP, 39 192 (65%) had only one procedure, 7105 (1%) had two procedures and 2009 (%) had three or more. For the identified CBD cohort 60 793 holecystectomies were performed over the study period with 17 063 patients having had both an ERCP and holecystectomy.
Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19
Authors: Mandeep R Mehra, Sapan S Desai, SreyRam Kuy, Timothy D Henry, Amit N Patel
Journal: New England Journal of Medicine (2020)

BackgroundCoronavirus disease 2019 (Covid-19) may disproportionately affect people with cardiovascular disease. Concern has been aroused regarding a potential harmful effect of angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in this clinical context.MethodsUsing an observational database from 169 hospitals in Asia, Europe, and North America, we evaluated the relationship of cardiovascular disease and drug therapy with in-hospital death among hospitalized patients with Covid-19 who were admitted between December 20, 2019, and March 15, 2020, and were recorded in the Surgical Outcomes Collaborative registry as having either died in the hospital or survived to discharge as of March 28, 2020.ResultsOf the 8910 patients with Covid-19 for whom discharge status was available at the time of the analysis, a total of 515 died in the hospital (5.8%) and 8395 survived to discharge. The factors we found to be independently associated with an increased risk of in-hospital death were an age greater than 65 years (mortality of 10.0%, vs. 4.9% among those ≤65 years of age; odds ratio, 1.93; 95% confidence interval [CI], 1.60 to 2.41), coronary artery disease (10.2%, vs. 5.2% among those without disease; odds ratio, 2.70; 95% CI, 2.08 to 3.51), heart failure (15.3%, vs. 5.6% among those without heart failure; odds ratio, 2.48; 95% CI, 1.62 to 3.79), cardiac arrhythmia (11.5%, vs. 5.6% among those without arrhythmia; odds ratio, 1.95; 95% CI, 1.33 to 2.86), chronic obstructive pulmonary disease (14.2%, vs. 5.6% among those without disease; odds ratio, 2.96; 95% CI, 2.00 to 4.40), and current smoking (9.4%, vs. 5.6% among former smokers or nonsmokers; odds ratio, 1.79; 95% CI, 1.29 to 2.47). No increased risk of in-hospital death was found to be associated with the use of ACE inhibitors (2.1% vs. 6.1%; odds ratio, 0.33; 95% CI, 0.20 to 0.54) or the use of ARBs (6.8% vs. 5.7%; odds ratio, 1.23; 95% CI, 0.87 to 1.74).ConclusionsOur study confirmed previous observations suggesting that underlying cardiovascular disease is associated with an increased risk of in-hospital death among patients hospitalized with Covid-19. Our results did not confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs with in-hospital death in this clinical context. (Funded by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women's Hospital.)
Relationship of a Claims-Based Frailty Index to Annualized Medicare Costs
Authors: Kenton J. Johnston, Hefei Wen, Karen E. Joynt Maddox
Journal: Annals of Internal Medicine (2020)

Medicare uses a standardized hierarchical condition category model to predict patients' annualized costs in value-based payment programs. The model may not work well in high-cost, high-need patient...