tbuckley/cabot-search huggingface dataset:
Tokyo Medical University admits rigging entrance exams against women
Authors: Owen Dyer
Journal: BMJ (2018)

One of Japan’s leading medical schools has been automatically reducing the entrance exam scores of female applicants by 20% for at least 12 years to graduate more male doctors, an independent inquiry has found.

Tokyo Medical University’s acting president, Keisuke Miyazawa, admitted to the exam rigging at a press conference on 7 August after the release of a damning report by external lawyers. “For those people whom we have caused tremendous hardship, especially female candidates whom we have hurt, we will do everything we can,” he said.

Miyazawa said that the school was considering options including financial compensation and retroactive admission of some women who would have passed without the automatic deduction. He said that he had not known of the score manipulation.

Tetsuo Yukioka, the school’s executive regent and chair of …
Abstract 16605: Alterations of a Cellular Cholesterol Metabolism Network is a Molecular Feature of Obesity-Related Type 2 Diabetes and Cardiovascular Disease
Authors: Jingzhong Ding, Lindsay M Reynolds, Tanja Zeller, Christian Muller, Kurt Lohman, Zhiqing Huang, Alberto de la Fuente, Nicola Soranzo, Robert E Settlage, Chia-Chi Chuang, Timothy Howard, Ning Xu, Mark O Goodarzi, Y.-D Ida Chen, Jerome I Rotter, David S Siscovick, John S Parks, Susan Murphy, David R Jacobs, Wendy Post, Russell P Tracy, Philipp S Wild, Stefan Blackenberg, Ina Hoeschele, David Herrington, Charles McCall, Yongmei Liu
Journal: Circulation (2014)

Obesity is linked to type 2 diabetes (T2D) and cardiovascular diseases; however, the underlying molecular mechanisms remain unclear. We aimed to identify obesity-associated molecular features that ...
Right-Sided Heart Wall Thickening and Delayed Enhancement Caused by Chronic Active Myocarditis Complicated by Sustained Monomorphic Ventricular Tachycardia
Authors: YoshiyukiHama, NobusadaFunabashi, MarehikoUeda, TomonoriKanaeda, MasaeUehara, KokiNakamura, TaichiMurayama, YokoMikami, HiroyukiTakaoka, MiyukiKawakubo, KwanghoLee, HiroyukiTakano, IsseiKomuro
Journal: Circulation (2009)
Abstract 17242: Effects of Tolvaptan on Early Outcomes for Patients Undergoing Cardiac Surgery and Predictors for its Responders
Authors: KazukiMorimoto, SatoshiNumata, SachikoYamazaki, KeiichiItatani, HidetakeKawajiri, SuguruOhira, HitoshiYaku
Journal: Circulation (2016)

Introduction: The efficacy of tolvaptan, a vasopressin V2 receptor antagonist, on refractory fluid retention after cardiac surgery is unknown. The aim of this study was to investigate the safety and efficacy of tolvaptan for fluid retention resistant to loop diuretics and predictors for responders after cardiac surgery. Methods: Between March 2014 and February 2016, 105 patients who underwent cardiac surgery in our hospital received tolvaptan 7.5mg orally in addition to furosemide 40mg because of remaining fluid retention. The beginning and duration of administration of tolvaptan was postoperative day 5.4±4.4 and 1.6±0.8 days, respectively. The responder to tolvaptan was defined as urine output of more than 2000 / 4000ml for 24 / 48 hours or body weight reduction of more than 0.5 / 1 kg for 24 / 48 hours after the administration. Early outcomes were compared between responders and non-responders. The predictors for responders were analyzed using multivariate logistic regression. Results: There were 70 res...
Radiopaque and uniform alginate microspheres loaded with tantalum nanoparticles for real-time imaging during transcatheter arterial embolization
Authors: Jian Zeng, Ling Li, Hongsen Zhang, Jianye Li, Lingli Liu, Guofeng Zhou, Qing Du, Chuansheng Zheng, Xiangliang Yang
Journal: Theranostics (2018)

One restriction to the development and application of transcatheter arterial chemoembolization (TACE) therapy is the lack of an inherently radiopaque embolic whose location and distribution can be precisely visualized in real time and be used for non-invasive examination after surgery. Methods: A one-step electrospray method was developed to fabricate calcium alginate microspheres loaded with tantalum nanoparticles (Ta@CaAlg). The parameters of electrospraying were assessed. The in vivo X-ray imaging capability and embolic effect of Ta@CaAlg microspheres were evaluated in the renal arteries of normal rabbits by digital radiography and computed tomography. Doxorubicin hydrochloride (Dox) was chosen as a model drug, and the drug loading capacity and release behavior of these microspheres was valuated in vitro.Results: Spherical Ta@CaAlg microspheres with monodisperse sizes ranging from 150 to 1200 μm were fabricated by electrospraying. The results of an in vivo study showed that Ta@CaAlg microspheres possessed the qualities of both embolic agents and contrast media. They could not only feed back the real-time location and distribution of the embolic microspheres but also maintained clear X-ray imaging of embolized sites for up to 4 weeks as assessed by digital radiography and computed tomography. Digital subtraction angiography showed that they had an excellent embolic effect. Ta@CaAlg microspheres could be loaded with Dox to form "3-in-1" embolic microspheres. The maximum Dox loading was 97.3 mg Dox per mL beads and loaded microspheres exhibited pH-dependent release profiles. Conclusion: The X-ray opacity and drug-loading capability of Ta@CaAlg microspheres offers great promise in direct, real-time, in vivo investigation for TACE and long-term non-invasive re-examination.
Abstract P364: Genetic Susceptibility to Particulate Matter-Associated QT Prolongation in a Trans-Ethnic Genome-Wide Association Study
Authors: RahulGondalia, On behalf ofMOPMAP
Journal: Circulation (2015)

Background: QT prolongation_an electrocardiographic risk factor for ventricular arrhythmia and sudden cardiac death_has both a genetic and environmental etiology. However, genetic susceptibility to particulate matter-associated QT interval (QT) prolongation has not been characterized. Methods: To characterize such susceptibility in a genome-wide association study, we conducted cohort-, race/ethnicity-, and sex-stratified longitudinal analyses of eight Women’s Health Initiative clinical trials (WHI CT) and Atherosclerosis Risk in Communities study (ARIC) subpopulations (total n: 20,595; mean age: 63.4 yrs; 77% female; 28% black; mean visits/person: 3.0). In each subpopulation, we used generalized estimating equation (GEE) methods adapted for small sample size to estimate interactive effects of dichotomized daily mean concentrations of ambient particulate matter   subpopulation-specific 90th percentiles) and approximately 2.5 million imputed single nucleotide polymorphisms (SN...
Regular Physical Exercise Corrects Endothelial Dysfunction and Improves Exercise Capacity in Patients With Chronic Heart Failure
Authors: RainerHambrecht, EduardFiehn, ClaudiaWeigl, StephanGielen, CarolineHamann, RalfKaiser, JiangtaoYu, VolkerAdams, JosefNiebauer, GerhardSchuler
Journal: Circulation (1998)

Background—The purpose of this study was to determine the effects of systemic exercise training on endothelium-mediated arteriolar vasodilation of the lower limb and its relation to exercise capacity in chronic heart failure (CHF). Endothelial dysfunction is a key feature of CHF, contributing to increased peripheral vasoconstriction and impaired exercise capacity. Local handgrip exercise has previously been shown to enhance endothelium-dependent vasodilation in conduit and resistance vessels in CHF. Methods and Results—Twenty patients were prospectively randomized to a training group (n=10, left ventricular ejection fraction [LVEF] 24±4%) or a control group (n=10, LVEF 23±3%). At baseline and after 6 months, peak flow velocity was measured in the left femoral artery using a Doppler wire; vessel diameter was determined by quantitative angiography. Peripheral blood flow was calculated from average peak velocity (APV) and arterial cross-sectional area. After exercise training, nitroglycerin-induced endotheli...
[<sup>18</sup>F]Fludarabine-PET as a promising tool for differentiating CNS lymphoma and glioblastoma: Comparative analysis with [<sup>18</sup>F]FDG in human xenograft models
Authors: Narinée Hovhannisyan, Fabien Fillesoye, Stéphane Guillouet, Méziane Ibazizene, Jérôme Toutain, Fabienne Gourand, Samuel Valable, Benoit Plancoulaine, Louisa Barré
Journal: Theranostics (2018)

This paper investigated whether positron emission tomography (PET) imaging with [18F]fludarabine ([18F]FDB) can help to differentiate central nervous system lymphoma (CNSL) from glioblastoma (GBM), which is a crucial issue in the diagnosis and management of patients with these aggressive brain tumors. Multimodal analyses with [18F]fluorodeoxyglucose ([18F]FDG), magnetic resonance imaging (MRI) and histology have also been considered to address the specificity of [18F]FDB for CNSL. Methods: Nude rats were implanted with human MC116 lymphoma-cells (n = 9) or U87 glioma-cells (n = 4). Tumor growth was monitored by MRI, with T2-weighted sequence for anatomical features and T1-weighted with gadolinium (Gd) enhancement for blood brain barrier (BBB) permeability assessment. For PET investigation, [18F]FDB or [18F]FDG (~11 MBq) were injected via tail vein and dynamic PET images were acquired up to 90 min after radiotracer injection. Paired scans of the same rat with the two [18F]-labelled radiotracers were investigated. Initial volumes of interest were manually delineated on T2w images and set on co-registered PET images and tumor-to-background ratio (TBR) was calculated to semi-quantitatively assess the tracer accumulation in the tumor. A tile-based method for image analysis was developed in order to make comparative analysis between radiotracer uptake and values extracted from immunohistochemistry staining. Results: In the lymphoma model, PET time-activity curves (TACs) revealed a differential response of [18F]FDB between tumoral and healthy tissues with average TBR varying from 2.45 to 3.16 between 5 to 90 min post-injection. In contrast, [18F]FDG demonstrated similar uptake profiles for tumoral and normal regions with TBR varying from 0.84 to 1.06 between these two time points. In the glioblastoma (GBM) model, the average TBRs were from 2.14 to 1.01 for [18F]FDB and from 0.95 to 1.65 for [18F]FDG. Therefore, inter-model comparisons showed significantly divergent responses (p < 0.01) of [18F]FDB between lymphoma and GBM, while [18F]FDG demonstrated overlap (p = 0.04) between the groups. Tumor characterization with histology (based mainly on Hoechst and CD79), as well as with MRI was overall in better agreement with [18F]FDB-PET than [18F]FDG with regard to tumor selectivity. Conclusions: [18F]FDB-PET demonstrated considerably greater specificity for CNSL when compared to [18F]FDG. It also permitted a more precise definition of target volume compared to contrast-enhanced MRI. Therefore, the potential of [18F]FDB-PET to distinguish CNSL from GBM is quite evident and will be further investigated in humans.
In Vitro and In Vivo Evaluation of Oral Heparin–Loaded Polymeric Nanoparticles in Rabbits
Authors: YuyanJiao, NathalieUbrich, MoniqueMarchand-Arvier, ClaudeVigneron, MauriceHoffman, ThomasLecompte, PhilippeMaincent
Journal: Circulation (2002)

Background— Owing to its short half-life and lack of oral absorption, heparin has to be administered by the parenteral route. An oral heparin formulation, however, would avoid the disadvantages of parenteral injections and would consequently be highly desirable for patients. Polymeric nanoparticles (NPs) prepared with biodegradable poly-e-caprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA) and nonbiodegradable positively charged polymers (Eudragit RS and RL), used alone or in combination, were evaluated in vitro and in vivo after a single oral administration of heparin-loaded NPs in rabbits. Methods and Results— After oral administration of heparin-loaded NPs in rabbits (600 IU/kg), increases in both anti–factor Xa activity and activated partial thromboplastin time (aPTT) were detected with each formulation. Moreover, the anti-Xa activity was detected for a longer period than when a heparin solution was administered intravenously. A peak concentration of 0.16±0.01 IU/mL and an average aPTT of 24 s...
Ryanodine Receptor Current Amplitude Controls Ca2+ Sparks in Cardiac Muscle
Authors: TaoGuo, DirkGillespie, MichaelFill
Journal: Circulation Research (2012)

Rationale:In cardiac muscle, Ca2+-induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR) is mediated by ryanodine receptor (RyR) Ca2+ release channels. The inherent positive feedback of CICR is normally well-controlled. Understanding this control mechanism is a priority because its malfunction has life-threatening consequences. Objective:We show that CICR local control is governed by SR Ca2+ load, largely because load determines the single RyR current amplitude that drives inter-RyR CICR. Methods and Results:We differentially manipulated single RyR Ca2+ flux amplitude and SR Ca2+ load in permeabilized ventricular myocytes as an endogenous cell biology model of the heart. Large RyR-permeable organic cations were used to interfere with Ca2+ conductance through the open RyR pore. Single-channel studies show this attenuates current amplitude without altering other aspects of RyR function. In cells, the same experimental maneuver increased resting SR Ca2+ load. Despite the increased load, Ca2+ spark ...
Abstract 3882: Functional validation of a genome-wide association study (GWAS) SNP associated with anthracycline-induced congestive heart failure
Authors: Xi Wu, Gloria Xue, Laura Gardner, Fei Shen, Guanglong Jiang, Santosh Philips, Geneva Cunningham, Bryan P. Schneider
Journal: Cancer Research (2018)

Abstract Anthracyclines are commonly used chemotherapies for the treatment of breast cancer, but they can cause dose-related cardiotoxicities and lead to congestive heart failure (CHF) in ~2% of patients. There are no clinically available predictive biomarkers for this toxicity. Previously we have identified and validated the association of a single nucleotide polymorphism (SNP), rs28714259, with CHF in three large adjuvant phase III breast cancer trials. rs28714259 locates in a putative glucocorticoid receptor (GR) binding site and the risk (minor) allele is predicted to disrupt GR binding. Interestingly, activation of GR-signaling by dexamethasone has been shown to protect cardiomyocytes from doxorubicin-induced apoptosis in rat. To test whether the risk allele affects GR binding efficiency in vitro, we performed electrophoretic mobility shift assay (EMSA) in MCF-7 and A549 cells. 100nM of dexamethasone for 4 hours induced a prominent band shift in either the major- or risk-allele probes. Notably, we observed a ~50% reduction in the shifted band intensity of risk-allele probes compared to major-allele probes, suggesting decreased binding in risk-allele probes. No additional supershift was detected after the binding reaction was co-incubated with a GR antibody. However, the previously shifted band was significantly diminished in both the major- and risk-allele probes, probably due to a conformational change induced by GR antibody and leading to the disruption of GR/DNA binding, which in turn suggests the observed shift was specifically caused by GR. Further validations are ongoing using cardiomyocytes derived from human induced pluripotent stem cells (iPSCs). These studies provide further insight into the function and role of rs28714259 in anthracycline-induced CHF. Citation Format: Xi Wu, Gloria Xue, Laura Gardner, Fei Shen, Guanglong Jiang, Santosh Philips, Geneva Cunningham, Bryan P. Schneider. Functional validation of a genome-wide association study (GWAS) SNP associated with anthracycline-induced congestive heart failure [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 3882.
Arginase Inhibition Improves Endothelial Function in Patients With Coronary Artery Disease and Type 2 Diabetes Mellitus
Authors: AlexeyShemyakin, OskarKövamees, ArnarRafnsson, FelixBöhm, PeterSvenarud, MagnusSettergren, ChristianJung, JohnPernow
Journal: Circulation (2012)

Background—Endothelial dysfunction plays an important role in the early development of atherosclerosis and vascular complications in type 2 diabetes mellitus. Increased expression and activity of arginase, metabolizing the nitric oxide substrate l-arginine, may result in reduced production of nitric oxide and thereby endothelial dysfunction. We hypothesized that inhibition of arginase activity improves endothelial function in patients with coronary artery disease (CAD) and type 2 diabetes mellitus. Methods and Results—Three groups of subjects were included: 16 patients with CAD, 16 patients with CAD and type 2 diabetes mellitus (CAD+Diabetes), and 16 age-matched healthy control subjects. Forearm endothelium-dependent and endothelium-independent vasodilatation were assessed with venous occlusion plethysmography before and during intra-arterial infusion of the arginase inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA; 0.1 mg/min). Nor-NOHA was also coinfused with the nitric oxide synthase inhibitor (NG-monomet...
Abstract 11982: Circulating Invariant Natural Killer T Cells are Decreased in Patients With Chronic Heart Failure
Authors: AkimichiSaito, NaokiIshimori, MikitoNishikawa, ShintaroKinugawa, HiroyukiTsutsui
Journal: Circulation (2014)

Objective: Inflammatory mediators play a crucial role in the development of chronic heart failure (HF). Invariant natural killer T (iNKT) cells, a unique subset of T lymphocytes, which recognize glycolipid antigens and secrete a large amount of T helper (Th) 1/Th2 cytokines on activation, function as immunomodulatory cells in the various pathological processes. We have demonstrated that iNKT cells have a protective role against the development of left ventricular (LV) remodeling and failure after myocardial infarction in mice. However, it remains unclear whether iNKT cells are involved in the development of HF in humans. Methods and Results: Nine HF patients (NYHA II or III, LV ejection fraction 26.3±3.0%) and 8 healthy controls were studied. The mean age and male gender were comparable between HF and controls (51.2±5.1 vs. 45.1±4.5 years and 77.8 vs. 75.0%). The causes of HF were idiopathic dilated cardiomyopathy in 3, ischemic in 2, and others in 4 patients. Plasma BNP was significantly higher in HF tha...
Abstract 2916: Targeting lysophospholipid metabolism inhibits pancreatic cancer cell proliferation under nutrient-limiting conditions
Authors: Petrus R. de Jong, Marco Maruggi, Alejandro D. Campos, Morgan A. Brand, Robert Lemos, David A. Scott, Sally A. Litherland, J. Pablo Arnoletti, Brian P. James, Garth Powis
Journal: Cancer Research (2018)

Abstract Patients with pancreatic ductal adenocarcinoma (PDAC) have a poor prognosis, and more effective systemic treatments for patients with local progression or metastasis (85% of cases) are needed. The pancreatic tumor microenvironment provides a rich source for novel drug targets. We aimed to identify and validate novel metabolic drug targets that are unique to hypoxic PDAC cells. Using bulk RNA sequencing in combination with metabolomics analyses in vitro, we previously found that PDAC cells negate the loss of intracellular unsaturated fatty acids in hypoxia by orchestrating the release of lysophospholipids (lyso-PLs) by cancer-associated fibroblasts, which are then taken up and stored in intracellular lipid droplets in hypoxic cancer cells. To confirm the relevance of these findings in vivo, we performed 3' droplet based single-cell RNA sequencing (scRNA-seq) combined with metabolomics analyses of intracellular and extracellular (tumor interstitial fluid) metabolites of MIAPaCa2 and patient-derived xenografts (PDX). Identification of cell lineages and subpopulations with hypoxic gene signatures was performed to correlate changes in metabolite levels with metabolic gene expression in vivo. This approach confirmed differential expression of lipid droplet-associated enzymes in hypoxic areas of the tumor, including lyso-PL acyl transferases (LPCAT1, LPCAT3), and phospholipases (LYPLA1, PLA2G15). We found that resistance of PDAC cell lines to pharmacologic treatment with inhibitors of fatty acid desaturases (FADS), reminiscent of hypoxia and nutrient starvation in vivo, was mediated by uptake of lyso-PLs from the medium. Importantly, genetic knockdown of LPCAT and LYPLA isoforms reversed the resistance to FADS inhibitors in culture in vitro and in vivo. Clinical relevance was demonstrated by mRNA expression analysis of PDAC patients from The Cancer Genome Atlas (TCGA) database, which showed that the expression of lyso-PL metabolizing genes is correlated with a significant worse prognosis (log-rank test, P=0.008). We are currently developing pharmacologic approaches to target LPCAT and LYPLA enzymes in hypoxic cancer cells as a novel approach for PDAC patients with unresectable disease. Citation Format: Petrus R. de Jong, Marco Maruggi, Alejandro D. Campos, Morgan A. Brand, Robert Lemos, David A. Scott, Sally A. Litherland, J. Pablo Arnoletti, Brian P. James, Garth Powis. Targeting lysophospholipid metabolism inhibits pancreatic cancer cell proliferation under nutrient-limiting conditions [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 2916.
Abstract 5773: Sequencing and cloning IDH1 R132H-targeted monoclonal T cell receptors from CD4+ T cells facilitated by opto-electric-positioning technology
Authors: Duane Smith, Payal Watchmaker, Guido Stadler, Natalie Marks, Yelena Bronevetsky, Keviin Chapman, Hideho Okada
Journal: Cancer Research (2018)

Abstract Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are enzymes that catalyze the conversion of isocitrate to α-ketoglutarate, while reducing NADH to NADPH. More than 80% of low-grade gliomas and secondary glioblastomas harbor point mutations in IDH. The R132H mutation is the most common mutation in IDH1, and vaccination with the mutant peptide elicited an MHC class II-specific antitumor response, suggesting mutant IDH1 as a potential target for immunotherapy (1). Discovering monoclonal T cell receptors (TCRs) that specifically recognize the R132H mutation is a key but challenging step towards viable immunotherapy for glioma/glioblastomas. Using opto-electric-positioning (OEP) technology in a chip-based, NanoPen culture environment, we have successfully identified and isolated a monoclonal T cell that specifically recognizes the R132H mutant IDH1 peptide. We cultured and identified monoclonal CD4+ T cells on chip, stimulated by monocyte-derived dendritic cells, pulsed with R132H IDH1 peptide. Activated, CD4+ T cells were selectively exported from the chip and their T-cell receptors (TCRs) were subsequently deep sequenced. The most likely pairs of alpha and beta TCR chains were cloned into mammalian expression vectors for functional validation in vitro, producing a TCR that specifically binds mutant IDH1 tetramer. Taken together, we show that the combined platform of the OEP and nanofluidic device provides a powerful solution to help identify cell type-specific, monoclonal T cells that can be exported and sequenced to reveal distinct TCRs, which in turn can be cloned, expressed and validated for future immunotherapies. Reference: 1. Schumacher et al., Nature 2014;512:324-27. Citation Format: Duane Smith, Payal Watchmaker, Guido Stadler, Natalie Marks, Yelena Bronevetsky, Keviin Chapman, Hideho Okada. Sequencing and cloning IDH1 R132H-targeted monoclonal T cell receptors from CD4+ T cells facilitated by opto-electric-positioning technology [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 5773.