tbuckley/cabot-search huggingface dataset:
Abstract 2258: Chromothripsis and survival in human malignancies
Authors: Aaron S. Mansfield, Enrique Garcia-Rivera
Journal: Cancer Research (2018)

Abstract Chromothripsis is a complex genomic event characterized by a high number of chromosomal rearrangements and copy number changes that typically localize to a specific region on a single chromosome. Next generation sequencing has led to the initial discovery and description of these events which have since been observed in multiple human cancers. Whereas most mutagenic processes occur gradually, the multiple structural variations of each chromothriptic event likely occur at once. The clinical significance of chromothripsis remains uncertain, so we sought to characterize the relationship between chromothripsis and survival across human malignancies. We analyzed 13,318 tumors of 36 types using publicly available data from The Cancer Genome Atlas with CTLPScanner, which uses a sliding window scan statistic to identify events consistent with a chromothripsis-like pattern (CTLP). Our cutoffs for CTLP of copy number variation ≥ 20 and a log10 likelihood ratio ≥ 8 were derived from a clinical training set previously described by CTLPScanner. We detected one or more events consistent with a CTLP in 8,276 tumors (62.1%) for a total 24,879 events. There were no events in 5,042 cases (37.86%), a significant decrease from established rates of CTLPs. CTLPs were more common in ovarian serous cystadenocarcinomas (89.8%), esophageal carcinomas (86.5%) and sarcomas (81.2%) than in thymomas (26.6%) and thyroid carcinomas (15.2%). Chromosomes 8, 1 and 6 were most frequently involved with CTLPs. CTLPs in chromosome 6 were associated with uveal melanoma, chromophobic renal cell carcinoma and cholangiocarcinomas whereas CTLPs involving chromosome 12 were associated with testicular germ cell tumors. Multiple CTLPs were found in 5,262 tumors (39.5%, range of events 2-18+) and were most common in ovarian serous cystadenocarcinomas and sarcomas. The presence of CTLPs was associated with diminished overall survival across all tumor types (HR 1.5, p&amp;lt;2e-16). Given the potential for multiple CTLPs to have a greater effect on outcomes, we compared the survival of patients whose tumors contained 3 or more CTLPs (n=3,255, 24.4%) to those with 0-1 or 2 CTLPs. The presence of 3 or more CTLPs was associated with the worst survival amongst these groups (HR 1.67, p&amp;lt;2e-16). We identified that CTLPs are common in human cancers despite their prior descriptions as rare events. This discrepancy is likely due to our detection parameters. In addition, we identified that having multiple co-occurring CTLPs is associated with a worse prognosis, suggesting this type of event is more clinically relevant than a single CTLP and can be used as a negative prognostic marker in human malignancies. Citation Format: Aaron S. Mansfield, Enrique Garcia-Rivera. Chromothripsis and survival in human malignancies [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 2258.
Abstract P067: Nut Consumption is Associated with a Lower Risk of Death among US Male Physicians
Authors: LucDjousse, AndrewPetrone, JohnGaziano
Journal: Circulation (2014)

Background: Previous studies have suggested that nut consumption, a good source of unsaturated fatty acids, magnesium, potassium, fiber, antioxidants, and vitamins is associated with a lower risk of coronary heart disease, type 2 diabetes, and sudden cardiac death. However, limited data are available on the association between nut intake and all-cause mortality. Objective: To test the hypothesis that nut consumption is inversely associated with the risk of all-cause mortality. Methods: A prospective cohort study of 20,742 male physicians from the Physicians’ Health Study. Nut intake was assessed between 1999 and 2002 using a food frequency questionnaire and deaths were ascertained by an endpoint committee. We used Cox regression to estimate multivariable adjusted relative risk of death according to nut consumption. In secondary analyses, we evaluated associations of nut consumption with cause-specific mortality (coronary heart disease, stroke, and cancer deaths). Results: During a median follow-up of 9.5 ...
Association of atopic dermatitis with depression, anxiety, and suicidal ideation in children and adults: A systematic review and meta-analysis
Authors: Amalie Thorsti Møller Rønnstad, Anne-Sofie Halling-Overgaard, Carsten R. Hamann, Lone Skov, Alexander Egeberg, Jacob P. Thyssen
Journal: Journal of the American Academy of Dermatology (2018)
Electrocardiographic Patterns in Man at High Altitudes
Authors: Andrésrotta, Andréslópez
Journal: Circulation (1959)

Electrocardiograms of healthy men both native and long-term residents at 14,900 feet above sea level have been obtained and classified according to their dominant pattern. Most of the tracings showed signs of either right ventricular hypertrophy or right bundle-branch block, incomplete and complete. Some of the mechanisms responsible for these electrocardiographic changes found at high altitudes, such as pulmonary hypertension, positional changes of the heart, and chronic hypoxia, are discussed.
Abstract 3862: Empowering research on ubiquitin and ubiquitin-like protein modification cascade using recombinant enzyme systems
Authors: Eric Yao, Shenshen Lai, Jun Yan
Journal: Cancer Research (2018)

Abstract Protein modifications by the covalent attachment of ubiquitin (Ub) or ubiquitin-like proteins (UBLs) such as SUMO, ISG15 or NEDD8 participate in many critical cellular processes. These include cell-cycle regulation, DNA repair, endocytosis, mitophagy, oncogenesis, post-membrane-protein trafficking, antiviral pathways and most notably, proteasomal degradation of target proteins. Ubiquitination and modification by UBLs share a similar catalytic cascade which requires the sequential action of three classes of enzymes: E1 activating enzymes, E2 conjugating enzymes and E3 ligases. While Ub/UBLs are activated by E1 through an ATP-dependent thioester bond formation and transferred to E2 from E1, the exact mechanism of how they are subsequently attached to a protein substrate depends on the type of E3's containing characteristic catalytic domain - RING, HECT or RBR. It has been generally accepted that E3's mediate substrate specificity and E2's are the main determinants for selection of the lysine to construct the modifier chains, which thereby directly control the cellular fate of the substrate. Recent research has linked dysregulation of the Ub/UBLs modification system to numerous diseases including cancer, immunological disorders and neurodegeneration. The high substrate specificity provided by combinations of over 30 E2's and over 600 E3's in the human genome makes these enzymes emerging drug targets. In response to a growing market demand, SignalChem has developed an extensive array of products encompassing enzymes, Ub/UBL modifiers and substrates in the ubiquitination, SUMOylation, ISGylation and NEDDylation processes. With Promega's AMP-GloTM reagents and an optimized assay protocol, we have identified and validated a variety of functionally competent combinations of these enzyme components. With the established protocol, each enzyme in the catalytic cascade has been assessed for their specific activity towards generation of free AMP. In addition, inhibition profiles of all three enzymes have been obtained using the assay system, further demonstrating their potential to be used in high-throughput screening to identify potential lead compounds for drug discovery and development programs. Citation Format: Eric Yao, Shenshen Lai, Jun Yan. Empowering research on ubiquitin and ubiquitin-like protein modification cascade using recombinant enzyme systems [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 3862.
KVLQT1 C-Terminal Missense Mutation Causes a Forme Fruste Long-QT Syndrome
Authors: ClaireDonger, IsabelleDenjoy, MyriamBerthet, NathalieNeyroud, CorinneCruaud, MohammedBennaceur, GuyChivoret, KettySchwartz, PhilippeCoumel, PascaleGuicheney
Journal: Circulation (1997)

Background KVLQT1, the gene encoding the α-subunit of a cardiac potassium channel, is the most common cause of the dominant form of long-QT syndrome (LQT1-type), the Romano-Ward syndrome (RWS). The overall phenotype of RWS is characterized by a prolonged QT interval on the ECG and cardiac ventricular arrhythmias leading to recurrent syncopes and sudden death. However, there is considerable variability in the clinical presentation, and potential severity is often difficult to evaluate. To analyze the relationship between phenotypes and underlying defects in KVLQT1, we investigated mutations in this gene in 20 RWS families originating from France. Methods and Results By PCR-SSCP analysis, 16 missense mutations were identified in KVLQT1, 11 of them being novel. Fifteen mutations, localized in the transmembrane domains S2-S3, S4-S5, P, and S6, were associated with a high percentage of symptomatic carriers (55 of 95, or 58%) and sudden deaths (23 of 95, or 24%). In contrast, a missense mutation, Arg555Cys, ide...
Sensitivity to Apoptosis Signal, Clearance Rate, and Ultrastructure of Fas Ligand-Induced Apoptosis in In Vivo Adult Cardiac Cells
Authors: KenjiHayakawa, GenzouTakemura, MasahikoKoda, YukinoriKawase, RumiMaruyama, YiwenLi, ShinyaMinatoguchi, TakakoFujiwara, HisayoshiFujiwara
Journal: Circulation (2002)

Background— Sensitivity to apoptotic signals, the clearance rate of apoptosis, and the apoptotic ultrastructure have not been studied in cells of the in vivo adult heart. Methods and Results— To minimize the systemic influence, soluble Fas ligand was injected directly into in vivo rat hearts and livers (as the control) at concentrations of 0, 0.5, 2, and 5 μg/mL (groups C, F0.5, F2, and F5). Apoptotic cardiomyocytes and apoptotic noncardiomyocytes of the heart were identified with similar incidences only in F5. Their incidences peaked at 12 hours after injection (2.0±0.09% in cardiomyocytes) and diminished markedly 24 hours later. Caspase-3 was activated only in F5. Boc-Asp-fmk, a pancaspase inhibitor, inhibited apoptosis, suggesting that the apoptosis sensitivity was regulated upstream of caspase-3. Apoptotic noncardiomyocytes showed typical ultrastructure. In addition to the typical ultrastructure, such as cellular shrinkage, chromatin condensation, and apoptotic bodies, however, apoptotic cardiomyocyte...
Abstract 4673: Selective delivery of tumor specific antigen to dendritic cells by mannose-labeled PLGA nanoparticles to induce immune response for cancer immunotherapy
Authors: Yeongseon Byeon, Ji Eun Won, Ga Hee Kim, Min Gi Kim, Yeong Min Park, Hee Dong HAN
Journal: Cancer Research (2018)

Abstract Objective: To overcome limitation of ex vivo manipulation against dendritic cells (DC) vaccines, we developed mannose-labeled poly(d,l-lactide-co-glycolide) nanoparticles (MN-PLGA-NPs). The MN-PLGA-NPs enabled selective delivery of tumor-specific antigen to mannose receptor overexpressed DCs without ex vivo manipulation. Methods: Conjugation of mannose (MN) and polyvinyl alcohol (PVA) was analyzed by H-NMR. Size and zeta potential of the MN-PLGA-NPs were examined by dynamic light scattering using an electrophoretic light scattering photometer. Selective delivery efficiency of MN-PLGA-NPs to DCs was examined by confocal microscope and flow cytometry. Migration of DCs containing MN-PLGA-NPs was assessed flow cytometry. Therapeutic efficacy of MN-PLGA(OVA+poly I:C)-NPs was examined in EG7 tumor-bearing mouse models. Biological effect and activated CD8+ T cells in tumor tissue were confirmed by immunohistochemistry assay. Results: Conjugation of MN and PVA was confirmed that the peaks for the CH2 of methylene group in PVA was observed at 1.48 ppm and 1.59 ppm, and CH of tetrahydropyran group in MN was observed at 3.40 ppm, 3.49 ppm, 3.76 ppm, and 5.41 ppm. Size and zeta potential of MN-PLGA-NPs were 200 nm formed spherical shape and -10 mV, respectively. Loading efficiency of OVA or poly I:C into MN-PLGA-NPs was 90 % or 45 %, individually. Intracellular uptake of MN-PLGA-NPs in DCs was increased through selective binding between MN and MN-receptor compared to PLGA-NPs. Additionally, DCs containing MN-PLGA-NPs exhibited efficient migration to popliteal lymph node. Therapeutic efficacy of MN-PLGA-NPs showed significant inhibition of tumor growth in EG7 tumor-bearing mice compared to the control (p &amp;lt; 0.001) and PLGA-NPs (p &amp;lt; 0.05), and showed 100% of survival up to 60 days. Additionally, MN-PLGA-NPs treatment group showed a greater number of activated CD8+ T cells in tumor tissue compared to the other groups (p &amp;lt; 0.001), and prevention effect of tumor growth resulted in effectively suppressed compared to the control (p &amp;lt; 0.001) or PLGA-NPs (p &amp;lt; 0.001). Conclusion: MN-PLGA-NPs is an attractive system that can directly activate DC in vivo without ex vivo manipulation, which overcome the limitation of existing DC vaccine. Keyword: dendritic cells, selective delivery, PLGA nanoparticle, cancer immunotherapy. Citation Format: Yeongseon Byeon, Ji Eun Won, Ga Hee Kim, Min Gi Kim, Yeong Min Park, Hee Dong HAN. Selective delivery of tumor specific antigen to dendritic cells by mannose-labeled PLGA nanoparticles to induce immune response for cancer immunotherapy [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 4673.
Abstract 19455: Risk Factor Changes Had a Minor Net Contribution to the Decline in Cardiovascular Mortality in the US, 1988-2004
Authors: Maria Tellez-Plaza, Roberto Pastor-Barriuso, Josep Redon, Ana Navas-Acien, Eliseo Guallar
Journal: Circulation (2015)

Introduction: The role of primary prevention and changes in risk factors in explaining cardiovascular disease (CVD) mortality trends is controversial. Previous studies did not consider simultaneous changes in multiple cardiovascular risk factors over time. Objectives: To evaluate the impact of changes in smoking, obesity, physical inactivity, hypertension, diabetes, chronic kidney disease and dyslipidemia to explain the decreasing trend in CVD mortality that occurred in the US from 1988-1994 to 1999-2004. Methods: Cohort study of 25,297 adult men and women ≥20 years old participating in the National Health and Nutrition Examination Survey (NHANES) III and 1999-2004 Mortality Follow-up. We used causal mediation analyses with additive hazard models to estimate the absolute and relative reductions in CVD mortality rates over time explained through risk factor changes. Results: CVD mortality rates in the US decreased from 1988-1994 to 1999-2004 by 52.7% in men and by 45.5% women. Net changes in CVD risk factors explained 12.6 and 10.9% of this decline in men and women, respectively. The reductions in smoking and in leisure time physical inactivity rates were the main factors explaining this decline. The increased in chronic kidney disease, however, independently attenuated the decline in CVD mortality in both men and women. Adjustment for changes in self-reported use of risk factor treatments did not materially change the findings. Conclusions: The net impact of changes in CVD risk factors on mortality changes in the US was small. While prevention strategies have intensified, increases in the prevalence of certain risk factors, such as chronic kidney disease, seem to attenuate the impact of primary prevention interventions. The mortality decline may have been driven by clinical interventions in patients with events, by secondary prevention, or by changes in non-traditional risk factors. Our findings also suggest that primordial prevention strategies are needed to control the increase recent trends in chronic kidney disease and to maximize the benefit of preventive interventions.
Abstract 11593: Thrombus Formation Under Flow is Inhibited by the Mechanosensitive Cation Channel Blockers GsMTx-4 Peptide and Gadolinium Chloride
Authors: Zeki Ilkan, Joy R Wright, Lorenza Francescut, Alison H Goodall, Martyn P Mahaut-Smith
Journal: Circulation (2015)

Introduction: Ion channels contribute significantly to platelet physiology, including control of Ca 2+ as a second messenger. Although there is a clear link between platelet activation and shear stress, no study has examined the functional relevance of mechanosensitive (MS) ion channels in platelets or their precursors, megakaryocytes. Hypothesis: Human platelets express MS cation channels such as Piezo1, which contribute to platelet function and the development of thrombosis. Methods: Thrombus formation and [Ca 2+ ] i (intracellular Ca 2+ ) responses were studied by confocal microscopy using the indicators DiOC 6 and Fluo-3, respectively, under physiological levels of shear stress in a parallel-plate flow chamber. Aggregation and [Ca 2+ ] i responses to collagen and thrombin in washed human platelets were assessed by light transmission aggregometry and Fura-2 ratiometric measurements. GsMTx-4 (2.5μM) and gadolinium chloride (GdCl 3 ) (30μM) were used as MS cation channel inhibitors, targeting Piezo1 and TRPC6 in platelets. Piezo1 mRNA and protein expression were studied in platelets and the megakaryocytic cell line Meg-01. Results: Both inhibitors significantly inhibited thrombus formation on a collagen surface under normal arterial shear rate (average thrombus volume was reduced from 48132.7±7739.4μm 3 to 13478.9±2744.8μm 3 by GdCl 3 (n=6, P&lt;0.01) and to 25125.9±6433.5μm 3 (n=6, P&lt;0.05) by GsMTx-4). GsMTx-4 also caused a reduction in thrombin-induced platelet aggregation (to 53.6±14.0% of control, n=4, P&lt;0.05), however GdCl 3 did not affect platelet shape change or aggregation under static conditions. Pre-treatment with either GsMTx-4 or GdCl 3 did not reduce calcium influx in response to TRPC6 stimulation with 60μM OAG, suggesting a MS role for Piezo1, which was found at the mRNA transcript and protein level in platelets and Meg-01 cells. Meg-01 cells showed shear rate-dependent increases in [Ca 2+ ] i levels; at a shear rate of 3989.2s -1 , F/F 0 increased to 1.38±0.05 from 1.00±0.00 baseline (n=53 cells, P&lt;0.0001), a response which was diminished by GsMTx-4, and by chelation of extracellular Ca 2+ by EGTA. Conclusions: We provide evidence for the first time for a functional contribution of MS cation channels in platelet physiology and thrombosis.
Abstract 16438: Elimination of Inappropriate Subcutaneous ICD Shocks by Using a Non-Absorbable Pouch When Non-Invasive Reprogramming Fails
Authors: Zeshan Ahmad, Andrew Williams, Marie Olsen, Sharon Kusne, Wilber Su
Journal: Circulation (2016)

Introduction: Subcutaneous ICD (S-ICD) sensing algorithms and program options differ from conventional ICDs. A nominal physical shift of the generator can frequently cause change in signal-to-noise...
Antisignal Recognition Particle Antibodies–Related Cardiomyopathy
Authors: MathildeThiébaut, BenjaminTerrier, SamiaMenacer, AliceBerezne, GuillaumeBussone, ClaireGoulvestre, RémiBellance, LoïcGuillevin, OlivierVignaux, LucMouthon
Journal: Circulation (2013)
Intrahepatic bile duct stone removal through endoscopic ultrasound-guided hepaticogastrostomy using novel basket catheter under digital cholangioscopy guidance
Authors: Takeshi Ogura, Atsushi Okuda, Akira Miyano, Nobu Nishioka, Kazuhide Higuchi
Journal: Endoscopy (2018)

Although the digital single-operator cholangioscope (SpyGlass DS, Boston Scientific, Marlborough, Massachusetts, USA) has clinical impact in various procedures, such as forceps biopsy or endoscopic hydraulic lithotripsy [1] [2] [3] [4], the small diameter of the working channel is one of the limitations of this scope. Recently, a novel basket catheter (Micro-Catch; MTW Endoskopie, Düsseldorf, Germany) has become available. This basket catheter, which has a sheath diameter of only 1 mm, can be inserted into the SpyGlass DS ([Fig. 1]). Herein, we describe intrahepatic bile duct stone removal using this basket catheter via SpyGlass DS through an endoscopic ultrasound (EUS)-guided hepaticogastrostomy (HGS) route.
Amiodarone Improves Cardiac Sympathetic Nerve Function to Hold Norepinephrine in the Heart, Prevents Left Ventricular Remodeling, and Improves Cardiac Function in Rat Dilated Cardiomyopathy
Authors: HitoshiTachikawa, MakotoKodama, KenichiWatanabe, ToshihiroTakahashi, MeileiMa, TakeshiKashimura, MasahiroIto, SatoruHirono, YujiOkura, KiminoriKato, HaruoHanawa, YoshifusaAizawa
Journal: Circulation (2005)

Background— It is unclear how amiodarone therapy exerts its effects on left ventricular remodeling and cardiac sympathetic nerve function in chronic heart failure. We investigated long-term effects of amiodarone on rat dilated cardiomyopathy after healing of cardiac myosin–induced autoimmune myocarditis. Methods and Results— Rats were treated with oral amiodarone or vehicle for 6 weeks. We determined cardiac function, left ventricular remodeling, and cardiac sympathetic nerve function with iodine-125–labeled metaiodobenzylguanidine ([I125]MIBG). Amiodarone treatment improved left ventricular pressure, central venous pressure, and rate of isovolumetric contraction and decreased ventricular weight (P<0.005). Expression of cytokine mRNA was unchanged; expression of atrial natriuretic peptide, collagen III, and transforming growth factor-β1 mRNA was decreased in amiodarone-treated rats (P<0.05). Phenotype of myosin heavy chain was moved toward that of normal rats by amiodarone. Initial myocardial uptake of MI...
Nitric Oxide Insufficiency, Platelet Activation, and Arterial Thrombosis
Authors: JosephLoscalzo
Journal: Circulation Research (2001)

Abstract—Nitric oxide (NO) was originally discovered as a vasodilator product of the endothelium. Over the last 15 years, this vascular mediator has been shown to have important antiplatelet actions as well. By activating guanylyl cyclase, inhibiting phosphoinositide 3-kinase, impairing capacitative calcium influx, and inhibiting cyclooxygenase-1, endothelial NO limits platelet activation, adhesion, and aggregation. Platelets are also an important source of NO, and this platelet-derived NO pool limits recruitment of platelets to the platelet-rich thrombus. A deficiency of bioactive NO is associated with arterial thrombosis in animal models, individuals with endothelial dysfunction, and patients with a deficiency of the extracellular antioxidant enzyme glutathione peroxidase-3. This enzyme catalyzes the reduction of hydrogen and lipid peroxides, which limits the availability of these reactive oxygen species to react with and inactivate NO. The complex biochemical reactions that underlie the function and in...