tbuckley/cabot-search huggingface dataset:
Abstract 4599: Detecting MSI phenotype in circulating blood DNA
Authors: Marc-Henri Stern, Amanda B. Silveira, Ivan Bieche, Samia Melaabi, Luc Cabel, Bruno Buecher, Jean-Yves Pierga, Francois-Clement Bidard, Charlotte Proudhon
Journal: Cancer Research (2018)

Abstract Background: Microsatellite instability (MSI) is a hypermutator phenotype occurring in gastrointestinal, endometrial and colorectal tumors, and more rarely, in urinary tract, ovarian, breast, prostate, lung, head and neck, liver and glioblastoma tumors. The diagnosis of MSI phenotype has recently emerged as the first pan-tumor biomarker likely to predict clinical benefit from immune-checkpoint blockade therapy, making its precise identification primordial for treatment decisions and disease monitoring. Current diagnosis of MSI is performed by multiplex PCR of five microsatellite markers, followed by capillary electrophoresis to detect shifts in allele size. An important limitation of this method is its low sensitivity preventing its use when tumor content is below 10%. Methods: We designed ddPCR assays examining 3 microsatellites. Analytical performance was assessed in vitro. Clinical performance was evaluated in a series of FFPE and body fluid DNA samples obtained from patients with Stage IV colorectal or endometrial carcinomas, previously classified as MSI-H or MSS using the standard pentaplex PCR method. Mutant allele frequencies (MAF) quantified with the ddPCR MSI assay were also compared with the MAFs reported by ddPCR assays targeting specific BRAF or PIK3CA mutations. Results: The ddPCR assays for the 3 microsatellites were found to have high specificity and reached a limit of detection of &amp;lt;0.1%. A perfect concordance with the MSI status determined by the pentaplex assay was observed in the 50 tumor samples tested (25 MSI-H and 25 MSS). Importantly, the ddPCR assays diagnosed the MSI phenotype in the plasma of all patients with MSI-H tumors, without false positives in MSS cases. Furthermore, an excellent correlation was observed in the 6 FFPE (R2:0.81) and 8 body fluid (R2:0.99) MSI-H samples were the MAFs measured by our assay could be compared with the ones obtained by ddPCR assays targeting specific mutations in BRAF or PIK3CA genes. Conclusion: This technique allows a cost-effective, sensitive and large scale screening of the MSI phenotype, as well as the follow-up of MSI patients using liquid biopsies. Citation Format: Marc-Henri Stern, Amanda B. Silveira, Ivan Bieche, Samia Melaabi, Luc Cabel, Bruno Buecher, Jean-Yves Pierga, Francois-Clement Bidard, Charlotte Proudhon. Detecting MSI phenotype in circulating blood DNA [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 4599.
Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans
Authors: KatherineEsposito, FrancescoNappo, RaffaeleMarfella, GiovanniGiugliano, FrancescoGiugliano, MyriamCiotola, LisaQuagliaro, AntonioCeriello, DarioGiugliano
Journal: Circulation (2002)

Background— Circulating levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are elevated in diabetic patients. We assessed the role of glucose in the regulation of circulating levels of IL-6, TNF-α, and interleukin-18 (IL-18) in subjects with normal or impaired glucose tolerance (IGT), as well as the effect of the antioxidant glutathione. Methods and Results— Plasma glucose levels were acutely raised in 20 control and 15 IGT subjects and maintained at 15 mmol/L for 5 hours while endogenous insulin secretion was blocked with octreotide. In control subjects, plasma IL-6, TNF-α, and IL-18 levels rose (P<0.01) within 2 hours of the clamp and returned to basal values at 3 hours. In another study, the same subjects received 3 consecutive pulses of intravenous glucose (0.33 g/kg) separated by a 2-hour interval. Plasma cytokine levels obtained at 3, 4, and 5 hours were higher (P<0.05) than the corresponding values obtained during the clamp. The IGT subjects had fasting plasma IL-6 and TNF-α levels ...
Scalloped Pupil in a Patient With Familial Amyloid Polyneuropathy
Authors: Bianca-Violeta Rusescu, Philippe Kerschen, Nico J. Diederich
Journal: JAMA Neurology (2018)

A 46-year-old man underwent liver transplant at the age of 29 years for familial amyloid polyneuropathy (FAP) because of a mutation at codon 30 of the transthyretin gene (TTR), resulting in a methionine for valine substitution (Val30Met). He presented to our neurology clinic with deterioration of his general condition, weight loss of 10 kg within 1 year, gait disturbances, and short episodes of loss of consciousness. On clinical examination, the right pupil was larger than the left (Figure, A and B). The left pupil also had irregular outlines. Light reflex was weak on both sides without light-near dissociation, suggesting impairment of the parasympathetic innervation of the pupil. Further ophthalmologic evaluation disclosed vitreous opacities. Intraocular pressure was normal.
Below Safety Limits, Every Unit of Glomerular Filtration Rate Counts: Assessing the Relationship Between Renal Function and Cancer-specific Mortality in Renal Cell Carcinoma
Authors: Alessandro Antonelli, Andrea Minervini, Marco Sandri, Roberto Bertini, Riccardo Bertolo, Marco Carini, Maria Furlan, Alessandro Larcher, Guglielmo Mantica, Andrea Mari, Francesco Montorsi, Carlotta Palumbo, Francesco Porpiglia, Paola Romagnani, Claudio Simeone, Carlo Terrone, Umberto Capitanio
Journal: European Urology (2018)
Decreasing miRNA sequencing bias using a single adapter and circularization approach
Authors: Sergio Barberán-Soler, Jenny M. Vo, Ryan E. Hogans, Anne Dallas, Brian H. Johnston, Sergei A. Kazakov
Journal: Genome biology (2018)

The ability to accurately quantify all the microRNAs (miRNAs) in a sample is important for understanding miRNA biology and for development of new biomarkers and therapeutic targets. We develop a new method for preparing miRNA sequencing libraries, RealSeq®-AC, that involves ligating the miRNAs with a single adapter and circularizing the ligation products. When compared to other methods, RealSeq®-AC provides greatly reduced miRNA sequencing bias and allows the identification of the largest variety of miRNAs in biological samples. This reduced bias also allows robust quantification of miRNAs present in samples across a wide range of RNA input levels.
Abstract P220: Apolipoprotein A1 May be Used as a Risk-marker for Future Chronic Kidney Disease in Middle-aged Men
Authors: Margareta I Hellgren, Bledar Daka, Charlotte A Larsson, Ulf Lindblad
Journal: Circulation (2016)

Aim: The aim was to describe the occurrence of chronic kidney disease stage 3 (CKD) in a middle-aged population in Sweden and the development over ten years time. We also aimed to examine the predictive value of lipoproteins. Method: A random sample of 2816 individuals (30-75 years) in a middle-sized town in southwestern Sweden, was examined in this population-based study. Fasting venous samples were drawn for s-creatinine, total cholesterol, HDL, LDL, ApolipoproteinA1 (ApoA1), ApolipoproteinB (ApoB) and triglycerides. Morning urine was collected for albumin and creatinine. The participants were examined with regard to blood pressure, body weight and height. After a mean follow-up time of 9.7 years, 1323 of the original participants were re-examined following the same protocol and in the analyses of occurrence of KKD. CKD was defined as eGFR ≤60 ml/min/1.73m2 (calculated with the CKD-Epi equation), and after excluding 28 participants with nephropathy at baseline and 37 participants due to missing data, 1267 individuals (632 men, 635 women) remained for further analyses regarding incident CKD. Results: Mean age at baseline was 48.9 years (SD 11.5) and mean BMI was 26.7 kg/m2 (SD 4.7). The occurrence of CKD increased from 2.1% at baseline to 8.3% after ten years. Baseline ApoA1 predicted CKD at follow-up when adjusted for age, BMI, systolic blood pressure and creatinine at baseline. There was a non-significant interaction between sex and ApoA1 in relation to CKD at baseline (p=0.151) and sex-stratified analyses showed a relationship in men but not in women. Neither ApoB, the ratio ApoB/ApoA, total cholesterol, HDL nor LDL had any predictive effect on CKD at follow-up when accordingly adjusted. Conclusion: The occurrence of CKD in this fairly young Swedish population was 2.1% at baseline, and increased fourfold after ten years follow-up. The results also show that ApoA1 may be used as a risk marker for the development of CKD, particularly in men, and may suggest a more aggressive treatment with statins in individuals at risk of kidney disease.
Abstract 2323: Involvement of glutamine in tolerance of human pancreatic cancer cell to inhibition of fatty acid synthesis
Authors: Koji Nishi, Mina Suzuki, Noriko Yamamoto, Yumiko Iwase, Nagahiko Yumita
Journal: Cancer Research (2018)

Abstract Pancreatic cancer (PC) is the fifth leading cause of cancer-related mortality in Japan. Although the standard chemotherapy regimens, FOLFIRINOX (fluorouracil, leucovorin, irinotecan and oxaliplatin), gemcitabine and nab-paclitaxel, are widely used to treat patients with advanced pancreatic cancer, their antitumor effects (progression and survival rates) are less potent against this cancer type than other solid tumors. Previously, we found that inhibition of acetyl-CoA carboxylase (ACC), a major rate-controlling enzyme of fatty acid synthetic pathway, suppressed the proliferation of PC cells. However, in this study, we found the tolerance to the inhibition in a part of PC cells. Therefore, we investigated the mechanism of the tolerance to ACC inhibition in PC cells. The human PC cell lines, AsPC-1, BxPC-3 and PANC-1 were obtained from the American Type Culture Collection. Live and apoptotic cell numbers were determined using the MUSE Annexin V and Dead Cell Kit according to the manufacturer's instructions. PANC-1 cells showed the tolerance to inhibition of fatty acid synthesis by ACC inhibitor, 5-(tetradecyloxy)-2-furoic acid (TOFA), whereas TOFA induced apoptosis in AsPC-1 and BxPC-3 cells. In addition, PANC-1 did not show autophagy even under the condition of fatty acid starvation. Next, we investigated whether PANC-1 has the tolerance to nutrient starvation in nutrient-depletion medium, Earle's Balanced Salt Solution (EBSS) and serum-free medium respectively. PANC-1 showed the survival even in such mediums, whereas AsPC-1 and BxPC-3 almost dead. This result suggests that the tolerance of fatty acid starvation of PANC-1 are related to that of nutrient starvation. Interestingly, proliferation of PANC-1 cultured in glutamine-depletion medium dramatically was suppressed, even though low glucose medium did not affect. BPTES, a selective inhibitor of glutaminase, also suppressed the proliferation and induced apoptosis in PANC-1, whereas there are little effects of 2-dexy-glucose, inhibitor of glycolysis, on them. These results suggest that the TCA cycle plays an important role on the tolerance to inhibition of fatty acid synthesis and nutrient starvation of PANC-1, and can be novel therapeutic target of PC cells which have the tolerance to nutrient starvation like PANC-1. Citation Format: Koji Nishi, Mina Suzuki, Noriko Yamamoto, Yumiko Iwase, Nagahiko Yumita. Involvement of glutamine in tolerance of human pancreatic cancer cell to inhibition of fatty acid synthesis [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 2323.
Adrenomedullin as a Novel Antimigration Factor of Vascular Smooth Muscle Cells
Authors: TakeshiHorio, MasakazuKohno, HiroakiKano, MiwakoIkeda, KenichiYasunari, KojiYokokawa, MiekoMinami, TadanaoTakeda
Journal: Circulation Research (1995)

Abstract The present study investigated the effect of adrenomedullin, a novel vasorelaxant peptide, on the migration of cultured rat vascular smooth muscle cells (SMCs) by using the Boyden-chamber method. Fetal calf serum (FCS) and platelet-derived growth factor (PDGF)–BB strongly stimulated SMC migration. Adrenomedullin clearly inhibited SMC migration stimulated with 5% and 10% FCS in a concentration-dependent manner. The migration induced by 10 and 25 ng/mL PDGF-BB was also inhibited by adrenomedullin in a concentration-dependent manner. Inhibition by adrenomedullin of FCS- and PDGF-induced SMC migration was paralleled by an increase in the cellular level of cAMP. In fact, the percent increase in cAMP level was strongly correlated with the percent decrease in migration activity of SMCs after treatment with adrenomedullin. 8-Bromo cAMP, a cAMP analogue, reproduced the inhibition by adrenomedullin of FCS- and PDGF-induced SMC migration. An activator of adenylate cyclase, forskolin, also reduced FCS- and P...
Abstract 14685: Efficacy of Combined Administration of Intracoronary Papaverine and Intravenous Adenosine 5’-Triphosphate in Assessment of Fractional Flow Reserve
Authors: TakeshiNishi, YoshihideFujimoto, YoshioKobayashi
Journal: Circulation (2014)

Purpose: Inducing maximal coronary hyperemia is important to measure fractional flow reserve (FFR) accurately. Administration of intracoronary (IC) papaverine and intravenous (IV) adenosine 5’-triphosphate (ATP) have been used to achieve maximal hyperemia in the assessment of FFR. However, they may not induce maximal hyperemia in all patients. We aimed to evaluate combined effect of IC papaverine and IV ATP on FFR measurements. Methods: FFR measurements using administration of IC papaverine (12 mg in the left coronary artery and 8 mg in the right coronary artery), IV ATP (140 μg/kg/min), and the combination of IC papaverine plus IV ATP (additional IC bolus infusion of papaverine during IV ATP) were performed in 57 lesions of 52 consecutive patients. FFR values, symptoms, development of atrioventricular block (AVB), and ventricular arrhythmia were recorded. Results: Mean FFR values with IC papaverine, IV ATP, and the combination of IC papaverine and IV ATP were comparable (0.75 ± 0.13 vs. 0.76 ± 0.13 vs. 0...
Lack of serological evidence of Middle East respiratory syndrome coronavirus infection in virus exposed camel abattoir workers in Nigeria, 2016
Authors: Ray TY So, Ranawaka APM Perera, Jamiu O Oladipo, Daniel KW Chu, Sulyman A Kuranga, Kin-ho Chan, Eric HY Lau, Samuel MS Cheng, Leo LM Poon, Richard J Webby, Malik Peiris
Journal: Eurosurveillance (2018)

Background Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic threat of global public health concern and dromedary camels are the source of zoonotic infection. Although MERS-CoV is enzootic in dromedaries in Africa as well as the Middle East, zoonotic disease has not been reported in Africa. Methods : In an abattoir in Kano, Nigeria, we tested nasal swabs from camels and investigated 261 humans with repeated occupational exposure to camels, many of whom also reported drinking fresh camel milk (n = 138) or urine (n = 94) or using camel urine for medicinal purposes (n = 96). Results : Weekly MERS-CoV RNA detection in January–February 2016 ranged from 0–8.4% of camels sampled. None of the abattoir workers with exposure to camels had evidence of neutralising antibody to MERS-CoV. Conclusion : There is a need for more studies to investigate whether or not zoonotic transmission of MERS-CoV does take place in Africa.
Abstract 3434: Digital spatial profiling platform allows for spatially resolved, high-plex quantification of mRNA distribution and abundance on FFPE and fresh frozen tissue sections
Authors: Daniel Zollinger, Kristina Sorg, Jill McKay-Fleisch, Kristi Barker, Karen Nguyen, Chris Merritt, Joseph Beechem
Journal: Cancer Research (2018)

Abstract Characterization of spatial mRNA expression across multiple targets in a single tissue section has proven difficult to accomplish. To address this unmet need, we have developed a novel imaging platform, Digital Spatial Profiling (DSP), designed to simultaneously analyze 10s to 100s of RNAs (or proteins) from discrete regions by detecting oligo-conjugated probes. We show that this system can resolve mRNA expression panels in a highly multiplexed and automated manner on human FFPE and fresh frozen tissues. DSP RNA probes consist of antisense target-recognition sequences and UV-cleavable tags that can be released in a precise manner by the DSP instrument and digitally counted using nCounter® reagents. For this, probes are first hybridized overnight in situ to human FFPE or fresh frozen tissue sections. After hybridization, tags are released by nondestructive exposure of UV light, automatically collected by the DSP Instrument, and quantified using nCounter® technology. The nCounter PlexSet™ reagents are used to enable the analysis of 96 regions of interest with a single nCounter run. To demonstrate the regional specificity of RNA detection on DSP, we profiled distinct regions in human tonsillitis tissues using a 48-plex of RNA target probes. Our results show that genes are detected in the expected region-specific manner. Using an orthogonal in situ hybridization (ISH) approach, we validate the RNA DSP results in tonsil across multiple targets. To determine the regionally specific RNA expression in tumor area and nontumor area in non-small cell lung cancer (NCSLC), we used a high-plex probe mix of relevant Immuno-oncology RNA targets. These results show that the DSP platform can be used to obtain high-plex, spatial RNA expression data on tissue sections. The protein profiling assay on DSP, presented elsewhere, depends upon FFPE-compatible antibodies, which can be difficult to generate for some targets. Utilizing spatial mRNA profiling provides an alternative for cases where the necessary antibodies do not exist. In all, simultaneous, high-plex RNA and protein detection with DSP on serial sections could provide a novel method that can bridge the gap between translational research discovery and clinical applications. Citation Format: Daniel Zollinger, Kristina Sorg, Jill McKay-Fleisch, Kristi Barker, Karen Nguyen, Chris Merritt, Joseph Beechem. Digital spatial profiling platform allows for spatially resolved, high-plex quantification of mRNA distribution and abundance on FFPE and fresh frozen tissue sections [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 3434.
Syndrome of Short P-R Interval with Abnormal QRS Complexes and Paroxysmal Tachycardia (Wolff-Parkinson-White Syndrome)
Authors: Louiswolff
Journal: Circulation (1954)

The syndrome of short P-R interval with abnormal QRS complexes and paroxysmal tachycardia occurs in otherwise healthy individuals in all age groups. Its interest and importance are related to our knowledge and concepts of the cardiac mechanism, the prevalence and clinical manifestations of paroxysmal tachycardia, the masking of the electrocardiographic signs of heart disease, and the serious consequences involved in making an incorrect diagnosis of heart disease. A single mechanism is in all probability responsible for the abnormal electrocardiogram and the paroxysmal tachycardia. Premature activation of a small fraction of ventricular musculature shortens the P-R interval and lengthens the QRS interval, thus accounting for the electrocardiographic peculiarities of the syndrome. Whether an anomaly of impulse formation or an anomaly of conduction is responsible for pre-excitation is not known, and the propensity to paroxysmal tachycardia can be explained on either basis. There is no evidence that hitherto ...
Abstract 187: Incidence, Timing and Duration of Newborn Resuscitations: Challenges for Implementation of International Treatment Recommendations
Authors: Dana E Niles, Elizabeth Foglia, Diana Kim, Ashley Murray, Ryan Olivere, Skare Christiane, Theresa Olasveengen, Anne Ades, Michael Posencheg, Vinay Nadkarni, Jo Kramer-Johansen
Journal: Circulation (2014)

INTRODUCTION: International consensus recommendations for newborn resuscitation allocate <60 seconds following birth to dry, stimulate, and assess heart rate and respirations before initiating time critical interventions such as positive-pressure ventilation (PPV). However, there is scarce data on the incidence, actual timing and duration of interventions for newborn resuscitations in a normal-risk delivery room. METHODS: Prospective, observational study conducted in the delivery unit at an academic training hospital. All deliveries during selected random weekday/evening 8-hours shifts were attended by a highly trained observer. Real-time data was collected on all newborns ≥32 weeks gestational age who received PPV immediately after birth. Time was recorded as from time of birth. Descriptive summaries were compared to international recommendations for time critical assessments and interventions. RESULTS: Between Jan-June 2014, 295 (22%) of 1372 live deliveries were observed. PPV was required in 22/295 (7%...
Abstract 16646: Invasive Assessment of Myocardial Bridging in Women and Men Presenting With Angina in the Absence of Obstructive Coronary Artery Disease
Authors: Vedant S Pargaonkar, Ingela Schnittger, Shigemitsu Tanaka, Ryotaro Yamada, Takumi Kimura, Ian Rogers, Jennifer A Tremmel
Journal: Circulation (2015)

Introduction: Up to 20% of patients with angina undergoing coronary angiography have no obstructive coronary artery disease (CAD). Myocardial bridging, while common in the population, is a potential cause of angina in this subset of patients. Hypothesis: We studied sex differences in the structural and hemodynamic characteristics of myocardial bridging in patients with angina in the absence of obstructive CAD. Methods: We identified a myocardial bridge (MB) in the left anterior descending artery by intravascular ultrasound (IVUS) in 62 women and 24 men with angina in the absence of obstructive CAD. A MB was defined as an echolucent half-moon sign and/or ≥10% systolic compression. We evaluated MB-related parameters, including total MB length, % arterial compression, and halo thickness, as well as minimum lumen area and plaque burden. Hemodynamic testing of the MB was performed using an intracoronary pressure/Doppler flow wire at rest and during dobutamine stress. We calculated diastolic fractional flow reserve (dFFR) (the ratio of diastolic intracoronary pressure divided by aortic pressure), as well as peak Doppler flow velocity. An abnormal dFFR was defined as ≤0.76 during dobutamine stress. Results: When compared with women, men had a longer length of myocardial bridging, more systolic compression, and a greater plaque burden proximal to the MB. There was no difference in halo thickness or MLA. There was also no sex difference in the dFFR or peak Doppler velocity change with stress (figure). Conclusions: While women are more likely than men to have angina in the absence of obstructive CAD, in patients with a MB as a possible cause of their angina, men have a longer length of bridge, more systolic compression, and greater plaque burden proximal to the MB than women. Interestingly, these more severe MB features in men do not result in more hemodynamic significance. Further research is needed to understand this sex difference.
The Influence of Standard of Living on Blood Pressure in Fiji
Authors: Ianmaddocks
Journal: Circulation (1961)

A group of Indian men in Suva, Fiji, selected for their relatively high standard of living had average systolic and diastolic blood pressures higher than those of the sample of the local rural Indian male population. There is gradation in the incidence of high blood pressure among several races of the Pacific Islands that parallels the degree to which they have been influenced by Western culture.