tbuckley/cabot-search huggingface dataset:
Regulation of Tissue Factor Expression in Human Microvascular Endothelial Cells by Nitric Oxide
Authors: YinkeYang, JosephLoscalzo
Journal: Circulation (2000)

Background—Tissue factor (TF) is a critical determinant of thrombin generation in normal hemostasis and in atherothrombotic disease. Nitric oxide has both antithrombotic and antiatherosclerotic actions in the vasculature, yet its role in the regulation of TF expression has not been examined. Methods and Results—To study the effect of endogenous endothelium-derived nitric oxide on TF expression and activity, we induced TF in human microvascular endothelial cells with lipopolysaccharide or interleukin-1β and observed a dose- and time-dependent increase in TF activity and expression by Northern and Western blotting. l-Arginine, the principal substrate for nitric oxide synthases, added to the media suppressed the induction of TF activity significantly (by 66% for lipopolysaccharide induction and by 59% for interleukin-1β induction) at 24 hours. These changes in activity were accompanied by correlative changes in TF protein and steady-state mRNA. d-Arginine had no effect, and inhibition of endogenous nitric ox...
Learning for Personalized Medicine: A Comprehensive Review From a Deep Learning Perspective
Authors: Sushen Zhang, Seyed Mojtaba Hosseini Bamakan, Qiang Qu, Sha Li
Journal: IEEE Reviews in Biomedical Engineering (2018)

With the recent advancements in analyzing high-volume, complex, and unstructured data, modern learning methods are playing an increasingly critical role in the field of personalized medicine. Personalized medicine (i.e., providing tailored medical treatment to individual patients through the identification of common features, including their genetics, inheritance, and lifestyle) has attracted the attention of many researchers in recent years. This paper provides an overview of the research progress in the application of learning methods, with a focus on deep learning in personalized medicine. In particular, three domains of applications are reviewed: drug development, disease characteristic identification, and therapeutic effect prediction. The main objective of this review is to consider the applied methods in detail and to offer insights into their pros and cons. Although having demonstrated advantages in coping with data complexity and nonlinearity and in recognizing features and associating structural data, the studied learning methods are not a panacea to all medical problems. Hence, we discuss the existing research challenges and clarify future study directions.
Nonconsensual Sexting and the Role of Sex Differences—Reply
Authors: Sheri Madigan, Joris Van Ouytsel, Jeff R. Temple
Journal: JAMA Pediatrics (2018)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal
IDH1-R132H acts as a tumor suppressor in glioma via epigenetic up-regulation of the DNA damage response
Authors: Felipe J. Núñez, Flor M. Mendez, Padma Kadiyala, Mahmoud S. Alghamri, Masha G. Savelieff, Maria B. Garcia-Fabiani, Santiago Haase, Carl Koschmann, Anda-Alexandra Calinescu, Neha Kamran, Meghna Saxena, Rohin Patel, Stephen Carney, Marissa Z. Guo, Marta Edwards, Mats Ljungman, Tingting Qin, Maureen A. Sartor, Rebecca Tagett, Sriram Venneti, Jacqueline Brosnan-Cashman, Alan Meeker, Vera Gorbunova, Lili Zhao, Daniel M. Kremer, Li Zhang, Costas A. Lyssiotis, Lindsey Jones, Cameron J. Herting, James L. Ross, Dolores Hambardzumyan, Shawn Hervey-Jumper, Maria E. Figueroa, Pedro R. Lowenstein, Maria G. Castro
Journal: Science Translational Medicine (2019)

Mutant IDH1 coexpressed with inactivating TP53 and ATRX mutations in glioma enhances DNA repair, causing resistance to genotoxic therapies.
Abstract 18982: Right Atrial Dysfunction From Speckle Tracking Strain Echocardiography Associated With Mortality in Patients With Pulmonary Hypertension.
Authors: Fawaz Alenezi, Aditya Mandawat, Irfan Siddiqui, Kristine Arges, Danny Rivera, Eric Velazquez, Pamela Douglas, Sudarshan Rajagopal, Zainab Samad
Journal: Circulation (2016)

Introduction: Right atrial (RA) size is an established marker for adverse outcomes in pulmonary arterial hypertension (PAH). Independent of RA size, RA function is impaired in PAH. However, the pro...
Abstract CT056: The first-in-human clinical trial of MG7-CART for metastasis colon cancer
Authors: Jijun Yuan
Journal: Cancer Research (2018)

Abstract MG7 antigen, a highly glycosylated CEACAM5 molecule, is specifically expressed in human gastrointestinal cancers. An MG7-CART therapy has been developed and showed great efficacy in gastric cancer PDX model. Here we present the first-in-human clinical trial results of MG7-CART therapy for metastasis colon cancer treatment. Distal metastasis was observed in pelvic cavity, peritoneal, spleen, liver and uterus after the patient received 6 rounds of bevacizumab plus EXLOX treatments. Intratumoral injections of MG7-CART (1-1.2x107/site) were given to the patient sequentially in peritoneal, spleen and uterus metastasis and two rounds of intravenous injections of MG7-CART (1x107 to 1.5x108) were given at the same time. Over 80% tumor necrosis could be observed in peritoneal and liver metastasis 40 days after injection and MG7-CART cell expansion could also be detected by PCR. During the treatment, the patient experienced transient body temperature increase and cytokine release. The first-in-human clinical trial result showed that MG7-CART therapy is efficacious and safe with no observed adverse effects. Citation Format: Jijun Yuan. The first-in-human clinical trial of MG7-CART for metastasis colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT056.
Hemodynamic Consequences of Induced Changes in Blood Volume
Authors: JamesConway, MiklosGellai
Journal: Circulation Research (1966)

The effects of transfusion or bleeding on cardiac output and blood pressure have been followed for periods of seven to ten hours in trained, conscious dogs. When blood volume is increased by transfusion of blood, supplemented by dextran to minimize the expected change in hematocrit, cardiac output and blood pressure increase initially. After one and one-half hours the cardiac output returns to the initial level but blood pressure remains elevated and calculated peripheral resistance increases. This state has been maintained for a period of ten hours by repeated transfusion. After bleeding, with replacement of packed cells, again to minimize the change in hematocrit, cardiac output decreases initially and peripheral resistance increases, but after three hours, output returns to its former level, and peripheral resistance falls below the control value. These changes become more prominent when a second hemorrhage is performed two hours after the first one. The reduction of resistance was then maintained for ...
Abstract 18687: PARP9 and PARP14 are Novel Regulators of Macrophage Activation
Authors: HiroshiIwata, HideoYoshida, PieroRicchiuto, TakuyaHara, IwaoYamada, AlexanderMojcher, PeterLibby, MarkBoothby, ElenaAikawa, SashaSingh, MasanoriAikawa
Journal: Circulation (2014)

Background: Pro-inflammatory “M1” macrophages may promote atherogenesis, while “M2” macrophages may favor an anti-inflammatory milieu. Our global proteomics of M1 and M2 cells identified ADP-ribosylation enzymes PARP9 and PARP14 as novel regulators of macrophage activation. The present study has examined the underlying mechanisms and explored in vivo evidence for their role in vascular disease. Methods and Results: IFN gamma (M1) stimulation induced and IL-4 (M2) decreased PARP9 and PARP14 in mouse and human macrophages. siRNA silencing of PARP14 enhanced expression of M1 genes (e.g. TNFα, iNOS) and activation (phosphorylation) of pro-inflammatory STAT1 while suppressing M2 markers (e.g., Arginase 1) and anti-inflammatory STAT6. Conversely, PARP9 silencing suppressed M1 polarization and STAT1 activation. These results suggest that PARP14 inhibits and PARP9 promotes a pro-inflammatory macrophage phenotype. Co-immunoprecipitation indicated that PARP14 and PARP9 physically interact. ADP-ribosylation assays r...
Abstract 13161: Incremental Prognostic Utility of Left Ventricular Global Longitudinal Strain in Asymptomatic/minimally Symptomatic Patients With Severe Bioprosthetic Aortic Stenosis Undergoing Redo Aortic Valve Replacement
Authors: Peyman Naji, Shailee Shah, Joseph F Sabik, Lars G Svensson, Zoran B Popovic, Leonardo L Rodriguez, Brian P Griffin, Milind Y Desai
Journal: Circulation (2016)

Introduction: With improved survival of patients undergoing primary bioprosthetic aortic valve replacement (AVR), reoperation to relieve severe prosthetic aortic stenosis (PAS) is increasing. Timing of redo surgery in asymptomatic/minimally symptomatic patients remains controversial. Left ventricular global longitudinal strain (LV-GLS) is a marker of subclinical LV dysfunction. In asymptomatic/minimally symptomatic patients with severe PAS undergoing redo AVR, we sought to determine if LV-GLS provides incremental prognostic utility. Methods: We studied 191 patients with severe bioprosthetic PAS (63±16 years, 58% men) who underwent redo-AVR between 2000-12 (excluding mechanical PAS, severe other valve disease transcatheter AVR, LV ejection fraction &lt;50%). Society of Thoracic Surgeons (STS) score was calculated. Standard echocardiography data was obtained. LV-GLS was measured on 2, 3 and 4-chamber views using Velocity Vector Imaging. Severe PAS was defined as AV area &lt;0.8 cm 2 , mean AV gradient ≥40 mm Hg and/or dimensionless index &lt;0.25. A composite outcome of death and congestive heart failure (CHF) admission was recorded. Results: At baseline, mean STS score, LV ejection fraction, mean AV gradients, right ventricular systolic pressure (RVSP) were 7±6, 58±6%, 54±10 mm Hg and 40±14 mm Hg, while 50% had &gt;II+ aortic regurgitation (AR). Median LV-GLS was -14.2% [-11.4, -17.1%]. At 4.2±3 years, 41 (22%) patients met the composite endpoint. The results of the multivariable Cox analysis are shown in Table 1. Kaplan-Meier survival curves separated based on median LV-GLS are shown in Figure 1. Incremental prognostic utility of LV-GLS over established predictors is shown in Figure 2. Conclusions: In asymptomatic/minimally symptomatic patients with severe bioprosthetic PAS undergoing redo AVR, baseline LV-GLS provides incremental prognostic utility over established predictors; and could potentially aid in surgical timing and risk stratification.
Expression and Function of Endothelial Ca2+-Activated K+ Channels in Human Mesenteric Artery
Authors: RalfKöhler, ChristianeDegenhardt, MeikeKühn, NorbertRunkel, MartinPaul, JoachimHoyer
Journal: Circulation Research (2000)

Abstract—Ca2+-activated K+ (KCa) channels have been suggested to play a role in the control of endothelial functions such as regulation of vascular tone and cell proliferation. We established a method for single-cell reverse transcriptase–polymerase chain reaction analysis in combination with the patch-clamp technique to characterize KCa channel expression and function in single endothelial cells (ECs) within the endothelial monolayer of intact human mesenteric arteries (MAs) and in disease states. We tested whether endothelial KCa channel expression and function are altered in MAs obtained from patients with colonic adenocarcinoma (CA) compared with those in MAs from non–cancer patients with inactive diverticulitis. Expression of the intermediate-conductance KCa channel (hIK1) was detected in non–cancer and CA patients. In whole-cell patch-clamp measurements, only ECs expressing hIK1 exhibited corresponding KCa currents, whereas respective KCa currents were missing in hIK1-negative ECs. This heterogeneit...
Potassium Channel Subunit Remodeling in Rabbits Exposed to Long-Term Bradycardia or Tachycardia
Authors: YukiomiTsuji, StephenZicha, Xiao-YanQi, ItsuoKodama, StanleyNattel
Journal: Circulation (2006)

Background— Sustained heart rate abnormalities produce electrical remodeling and susceptibility to arrhythmia. Uncontrolled tachycardia produces heart failure and ventricular tachyarrhythmia susceptibility, whereas bradycardia promotes spontaneous torsade de pointes (TdP). This study compared arrhythmic phenotypes and molecular electrophysiological remodeling produced by tachycardia versus bradycardia in rabbits. Methods and Results— We evaluated mRNA and protein expression of subunits underlying rapid (IKr) and slow (IKs) delayed-rectifier and transient-outward K+ currents in ventricular tissues from sinus rhythm control rabbits and rabbits with AV block submitted to 3-week ventricular pacing either at 60 to 90 bpm (bradypaced) or at 350 to 370 bpm (tachypaced). QT intervals at matched ventricular pacing rates were longer in bradypaced than tachypaced rabbits (eg, by ≈50% at 60 bpm; P<0.01). KvLQT1 and minK mRNA and protein levels were downregulated in both bradypaced and tachypaced rabbits, whereas ERG ...
Nanoparticle-Mediated Delivery of Pitavastatin Inhibits Atherosclerotic Plaque Destabilization/Rupture in Mice by Regulating the Recruitment of Inflammatory Monocytes
Authors: ShunsukeKatsuki, TetsuyaMatoba, SoichiNakashiro, KeiSato, Jun-ichiroKoga, KakuNakano, YasuhiroNakano, ShizukaEgusa, KenjiSunagawa, KensukeEgashira
Journal: Circulation (2014)

Background—Preventing atherosclerotic plaque destabilization and rupture is the most reasonable therapeutic strategy for acute myocardial infarction. Therefore, we tested the hypotheses that (1) inflammatory monocytes play a causative role in plaque destabilization and rupture and (2) the nanoparticle-mediated delivery of pitavastatin into circulating inflammatory monocytes inhibits plaque destabilization and rupture. Methods and Results—We used a model of plaque destabilization and rupture in the brachiocephalic arteries of apolipoprotein E–deficient (ApoE−/−) mice fed a high-fat diet and infused with angiotensin II. The adoptive transfer of CCR2+/+Ly-6Chigh inflammatory macrophages, but not CCR2−/− leukocytes, accelerated plaque destabilization associated with increased serum monocyte chemoattractant protein-1 (MCP-1), monocyte-colony stimulating factor, and matrix metalloproteinase-9. We prepared poly(lactic-co-glycolic) acid nanoparticles that were incorporated by Ly-6G−CD11b+ monocytes and delivered ...
Human Corneal Tissue Model for Nociceptive Assessments
Authors: Wang Siran, Chiara E. Ghezzi, Dana M. Cairns, Rachel E. Pollard, Ying Chen, Rachel Gomes, Tina B. McKay, Dimitra Pouli, Arsia Jamali, Irene Georgakoudi, James L. Funderburgh, Kenneth Kenyon, Pedram Hamrah, David L. Kaplan
Journal: Advanced Healthcare Materials (2018)

Abstract New in vitro tissue models to mimic in vivo conditions are needed to provide insight into mechanisms involved in peripheral pain responses, potential therapeutic strategies to address these responses, and to replace animal models for such indications. For example, the rabbit cornea Draize test has become the standard method used for decades to screen ophthalmic drug and consumer product toxicity. In vitro tissue models with functional innervation have the potential to replace in vivo animal testing and provide sophisticated bench tools to study ocular nociception and its amelioration. Herein, full thickness, innervated, 3D human corneal tissues are grown under physiologically relevant culture conditions to study nociceptive‐related responses, by mimicking ocular environmental cues, including intraocular pressure (IOP) and tear flow (TF). Capsaicin, a chili pepper‐derived irritant known to cause a burning sensation in mammalian tissues is utilized as a nociceptive stimulant to induce pain, while subsequent serum treatment is used to mimic healing. Pain mediators released upon capsaicin stimulation and cell regrowth after serum treatment are characterized to assess ocular responses in this new, innervated, human corneal tissue system for comparison of outcomes to established animal and related responses.
Erratum: Corrigendum: The transcription factor T-bet is essential for the development of NKp46+ innate lymphocytes via the Notch pathway
Authors: Lucille Rankin, Joanna R Groom, Michaël Chopin, Marco J Herold, Jennifer A Walker, Lisa A Mielke, Andrew N J McKenzie, Sebastian Carotta, Stephen L Nutt, Gabrielle T Belz
Journal: Nature Immunology (2013)
A Comparison between the Compass Fundus Perimeter and the Humphrey Field Analyzer
Authors: Giovanni Montesano, Susan R. Bryan, David P. Crabb, Paolo Fogagnolo, Francesco Oddone, Allison M. McKendrick, Andrew Turpin, Paolo Lanzetta, Andrea Perdicchi, Chris A. Johnson, David F. Garway-Heath, Paolo Brusini, Luca M. Rossetti
Journal: Ophthalmology (2018)
Glutamate-Weighted Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Detects Glutaminase Inhibition in a Mouse Model of Triple-Negative Breast Cancer
Authors: Rong Zhou, Puneet Bagga, Kavindra Nath, Hari Hariharan, David A. Mankoff, Ravinder Reddy
Journal: Cancer Research (2018)

Glutamate is an important metabolite of glutaminolysis, a metabolic pathway used by many aggressive cancers, including triple-negative breast cancer (TNBC). With the exception of the brain, in vivo detection of glutamate in tissues using 1H magnetic resonance spectroscopy (MRS) is challenging. Compared with MRS, glutamate-weighted chemical exchange saturation transfer MR imaging (GluCEST MRI) offers a more sensitive detection mechanism that is free of glutamine interference. Here, we developed a robust, highly repeatable GluCEST MRI protocol in mice bearing human TNBC xenografts and treated with a potent glutaminase inhibitor, CB-839. In paired studies, treatment with CB-839 for 2 days reduced the GluCEST asymmetry value compared with baseline (P < 0.05, n = 10). The absolute change of the GluCEST asymmetry value was -2.5 percent points after CB-839 treatment versus +0.3 after vehicle (P < 0.01). Correspondingly, treatment with CB-839 reduced tumor glutamate concentrations by 1.5 mmol/L, consistent with prior calibration between changes of the GluCEST value versus tissue glutamate concentration; CB-839, however, did not change tumor intracellular pH. These results demonstrate in a mouse model of breast cancer the utility of GluCEST MRI to detect the early response to glutaminase inhibition.Significance: A sensitive method enables noninvasive detection of tumor response to inhibitors of glutamine metabolism. Cancer Res; 78(19); 5521-6. ©2018 AACR.
His Bundle Electrograms in Two Cases of Wolff-Parkinson-White (Pre-excitation) Syndrome
Authors: Agustincastellanos, Eduardochapunoff, Cesarcastillo, Orlandomaytin, Louislemberg
Journal: Circulation (1970)

The catheter technic for recording the electrical activity of the specialized conducting system in the human heart showed in two patients studied that ventricular pre-excitation was apparently due to a bypass of the His bundle. Intermediate forms of WPW complexes appeared to be combination beats resulting from the activation of the ventricles through impulses traversing both the His bundle and accessory communications. Preferential iatrogenic activation of an intra-atrial (and perhaps even of an atrioventricular) tract appeared to occur in one of the patients. The patients with the WPW (pre-excitation) syndrome and long histories of paroxysmal arrhythmias were successfully treated with a combination of oral propranolol and implanted (transvenous) demand pacemaker.
Abstract 12026: Nocturnal Blood Pressure Burden, Diuretics, and Cardiac Load: Determinants of Nocturia in the Japanese at High-Risk of Cardiovascular Disease
Authors: Michiaki Nagai, Satoshi Niijima, Satoshi Hoshide, Mami Takahashi, Masahisa Shimpo, Kazuomi Kario
Journal: Circulation (2015)

Introduction: The majority of epidemiologic studies reported a significant relationship between hypertension and nocturia. However, the underlying pathophysiology has not been established. Hypothesis: We hypothesized that nocturnal blood pressure (BP) burden, some classes of antihypertensive agents and cardiac load might be associated with severity of noctria. In this study, the relationships of nocturia with self-measured home BP (HBP), the class of antihypertensive agent, B-type natriuretic peptide (BNP) were investigated in the Japanese at high-risk of cardiovascular disease. Methods: Among 4310 patients with one or more cardiovascular risks recruited for the Japan Morning Surge-Home Blood Pressure Study, the measurements of HBP at morning, evening, and nighttime as well as BNP were performed in the 2785 patients (63.5 years old, male 48.9%). A self-administered questionnaire included items on nocturia was used. Results: According to the number of nocturia (no void: n= 1571; one void: n=557; 2 or more voids per night: n=657), significant associations of systolic BP (SBP) at morning (136 vs 136 vs 140 mmHg, p&lt;0.001), evening (129 vs 129 vs 131 mmHg, p&lt;0.01) and nighttime (120 vs 120 vs 125 mmHg, p&lt;0.001) as well as logBNP (1.15 vs 1.26 vs 1.39, p&lt;0.001) were observed with nocturia severity. In the multinomial logistic regression analysis adjustment for confounders including age, smoking, total cholesterol, fasting blood glucose and HbA1c, the use of diuretics (OR: 1.28, 95%CI: 1.01-1.61, p&lt;0.05) was significantly associated with one nocturnal void, while nighttime SBP (OR: 1.012, 95%CI: 1.01-1.02, p&lt;0.001) and logBNP (1.46, 95%CI: 1.16-1.84, p&lt;0.01) were significantly associated with multiple nocturnal voids. A significant interaction was found between nighttime SBP and logBNP for multiple nocturnal voids (p&lt;0.01). On the other hand, neither morning SBP nor evening SBP had a significant relationship with nocturia. Conclusions: In this study, nighttime SBP and BNP were synergetically associated with severe nocturia in the high-risk Japanese population. Antihypertensive treatment to reduce BP burden during sleep as well as cardiac overload might be important to improve sleep quality caused by nocturia.
Dealing with serious concerns: catch the three wise monkeys
Authors: Andrew J Ashworth
Journal: BMJ (2018)

The immediate corporate response to concerns is typically to ignore the whistleblower. Matters are rarely investigated, and, when they are, tackling systemic deficiencies has a lower priority than finding a scapegoat. 

Shipman, Stafford, and Gosport are examples of the “three wise monkeys” management technique. Concerns were raised and ignored about Shipman earlier in his criminal career (hear no evil). Managers at Stafford failed …