tbuckley/cabot-search huggingface dataset:
Abstract 1233: Reducing sequence artifact in clinical sequencing of treatment-naïve NSCLC patient using molecular barcoding system
Authors: Kei Namba, Shuta Tomida, Yuta Takahashi, Eisuke Kurihara, Yusuke Ogoshi, Takahiro Yosioka, Hidejiro Torigoe, Hiroki Sato, Kazuhiko Shien, Hiromasa Yamamoto, Junichi Soh, Shinichi Toyooka
Journal: Cancer Research (2018)

Abstract Background: Recently the clinical significance of compound mutations in cancer relapse and/or acquired resistance has been reported. Amplicon-based deep sequence enables analysis of tiny amount of input DNA, however, a major problem of these high-throughput DNA sequencing is the high rate (~1%) of errors causing potential sequence artifact. Molecular barcoding system, which has been developed to reduce sequencing artifacts as well as to improve mutation detection accuracy, was applied to analyze the frequency of compound EGFR mutations in early stage non-small-cell lung cancer (NSCLC) patients who undergo surgical resection without any presurgical treatment is less described. Materials and Methods: From 590 consecutive patients, 64 adenocarcinoma cases who underwent surgical resection for primary lung cancer were analyzed by using amplicon-based targeted sequencing method incorporating molecular barcodes in order to detect genetic alterations of 47 genes including EGFR. Results: Out of 64 samples, EGFR common mutation profiles of 63 (98.4%) by molecular-barcode sequencing corresponded to those by clinical test. Uncommon EGFR mutations were detected in 7 cases (10.9%). Among the three types of EGFR major mutation, G719X (60%, 3/5) showed a significantly higher incidence of EGFR double mutations than L858R (9.5%, 4/42) or Ex19del (0%, 0/17) (p = 0.0052). Co-mutations of other genes were observed in 20 EGFR-mutated cases. TP53 mutations were frequently detected in younger age (p = 0.0066) and pStage II-III cases (p = 0.042). Conclusion: Amplicon sequencing incorporating molecular barcoding system is a feasible approach to characterize predictive or prognostic mutations in early stage treatment naïve NSCLC patients, revealing those case who harbor EGFR G719X mutation have a significantly higher incidence of EGFR double mutations, likely to have worse prognosis. Citation Format: Kei Namba, Shuta Tomida, Yuta Takahashi, Eisuke Kurihara, Yusuke Ogoshi, Takahiro Yosioka, Hidejiro Torigoe, Hiroki Sato, Kazuhiko Shien, Hiromasa Yamamoto, Junichi Soh, Shinichi Toyooka. Reducing sequence artifact in clinical sequencing of treatment-naïve NSCLC patient using molecular barcoding system [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 1233.
Abstract 17175: Phoshodiesterase 2 - A New Member Of Proteins Involved In Beta-adrenergic Desensitization
Authors: Christiane Vettel, Hind Mehel, Julius Emons, Katrin Wittkoepper, Danilo Seppelt, Matthias Dewenter, Susanne Lutz, Samuel Sossalla, Lars S Maier, Patrick Lechene, Jerome Leroy, Florence Lefebvre, Audrey Varin, Thomas Eschenhagen, Stanley Nattel, Dobromir Dobrev, Wolfram-Hubertus Zimmermann, Viacheslav O Nikolaev, Grégoire Vandecasteele, Rodolphe Fischmeister, Ali El-Armouche
Journal: Circulation (2013)

Diminished cAMP- and augmented cGMP-signaling is characteristic for failing hearts. Among the PDE superfamily, phosphodiesterase 2 (PDE2) has the unique property to be stimulated by cGMP, but prima...
Endoscopic retrieval of a lumen-apposing metal stent complicated by inward migration after cystogastrostomy
Authors: Neal Mehta, Ashraf Abushahin, Matheus Franco, Tyler Stevens, Prabhleen Chahal, John Vargo, Amit Bhatt
Journal: Endoscopy (2018)

Endoscopic ultrasound (EUS)-guided drainage is well known as an established technique for the treatment of pancreatic pseudocysts [1] [2]. New covered metal stents, known as lumen-apposing metal stents (LAMS), have been designed. Despite their superior antimigration features, these LAMS can migrate inwardly [3] [4]. We report a case of successful endoscopic retrieval of a LAMS with inward migration after cystogastrostomy.
Thy-1 (CD90) promotes bone formation and protects against obesity
Authors: Ann-Kristin Picke, Graeme M. Campbell, Matthias Blüher, Ute Krügel, Felix N. Schmidt, Elena Tsourdi, Maria Winzer, Martina Rauner, Vladimir Vukicevic, Björn Busse, Juliane Salbach-Hirsch, Jan P. Tuckermann, Jan C. Simon, Ulf Anderegg, Lorenz C. Hofbauer, Anja Saalbach
Journal: Science Translational Medicine (2018)

Thy-1 on mesenchymal stem cells promotes osteogenesis while inhibiting adipogenesis and obesity.
Angiotensin II Stimulates Platelet-Derived Growth Factor-B Chain Expression in Newborn Rat Vascular Smooth Muscle Cells and Neointimal Cells Through Ras, Extracellular Signal–Regulated Protein Kinase, and c-Jun N-Terminal Protein Kinase Mechanisms
Authors: Jun-oDeguchi, MasatoshiMakuuchi, TakashiNakaoka, TuckerCollins, YohTakuwa
Journal: Circulation Research (1999)

Abstract—Platelet-derived growth factors (PDGFs) have been implicated in the pathogenesis of vascular proliferative disorders. Vascular smooth muscle cells (VSMCs) are one of the cell types that produce PDGF-B chain in proliferative lesions, although the mechanism of regulation of PDGF-B chain production in these cells is not well understood. In the present study, we demonstrate that angiotensin II (Ang II), which is also implicated in vascular stenosis after angioplasty and atherosclerosis, markedly stimulates PDGF-B chain mRNA expression in cultured newborn rat medial VSMCs and neointimal VSMCs via an AT1, but not in adult rat VSMCs. In newborn rat VSMCs, Ang II activates extracellular signal–regulated protein kinase (ERK), c-Jun N-terminal protein kinase (JNK), and p38 mitogen–activated protein kinase. The mitogen-activated protein/ERK (MEK) inhibitor PD98059, but not the p38 inhibitor SB203580, abrogates Ang II–induced PDGF-B mRNA expression. Transient transfection analysis using a PDGF-B promoter-luc...
Abstract 18925: The Serum Level of Mir-30a-3p And Mir-31-5p Can Discriminate Responders From Non-responders to CD34 + Cell Therapy in Patients With Dilated Cardiomyopathy
Authors: Tadej Pajic, Nika Klinec, Matjaz Sever, Peter Cernelc, Gregor Poglajen, Francois Haddad, Bojan Vrtovec
Journal: Circulation (2015)

Introduction: The potential predictive value of specific, circulating miRNAs in blood in patiens with non-ischemic dilated cardiomyopathy (DCM) undergoind CD34+ cell therapy remains undefined. Hypothesis: We assessed the hypothesis that the relative level of specific miRNAs in serum obtained at baseline will discriminate responders from non-responders to stem cell therapy in patients with DCM. Methods: We enrolled 10 consecutive patients with DCM who underwent transendocardial CD34+ cell transplantation between January and December 2013. All patients received 5-day stimulation with G-CSF; CD34+ cells were selected with apheresis and injected transendocardially guided by electroantomical mapping. Patients were followed for 6 months and good clinical response was defined as an increase of left ventricular ejection fraction (LVEF) ≥5%. Before cell therapy, total RNA was isolated from serum with the miRCURY RNA Isolation Biofluids Kit. cDNA synthesis and real-time qPCR were performed using the miRCURY Locked Nucleic Acid and Universal RT microRNA PCR system with The qPCRs were run on a ViiA7 thermocycler. Results: At 6 months after therapy, good clinical response was found in 5 patients (Group A), and 5 patients failed to respond to cell therapy (Group B). The two groups did not differ with regards to age (55±9 years in Group A vs. 57±3 years in Group B; P=0.58), male gender (87% vs. 100%; P=0.34), baseline LVEF (33±5% vs. 28±8%; P=0,28), LVEDD (6.6±0.4 cm vs. 6.9±0.7 cm; P=0.33) or NTproBNP levels (1460±932 pg/mL vs. 4540±3808 pg/mL; P=0.15). When analyzing the pool of miRNAs we found the serum level of miR-30a-3p and miR- 31-5p to be significantly different between two study groups (both had adjusted P values of 0.031). The serum level of miR- 31-5p was higher in the group of responders (log2 fold change of 6.78) while the serum level of miR-30a-3p was higher in the group of non-responders (log2 fold change of 4.98). Conclusions: In patients with DCM undergoing CD34+ cell therapy specific serum miRNAs appear to discriminate clinical responders from non-responders. Therefore, they could be used as a tool when selecting appropriate patients for stem cell therapy.
Sex-Biased Physiological Roles of NPFF1R, the Canonical Receptor of RFRP-3, in Food Intake and Metabolic Homeostasis Revealed by its Congenital Ablation in mice
Authors: Silvia Leon, Inmaculada Velasco, Maria J. Vázquez, Alexia Barroso, Daniel Beiroa, Violeta Heras, Francisco Ruiz-Pino, Maria Manfredi-Lozano, Antonio Romero-Ruiz, Miguel A. Sanchez-Garrido, Carlos Dieguez, Leonor Pinilla, Juan Roa, Ruben Nogueiras, Manuel Tena-Sempere
Journal: Metabolism (2018)
Optimization of <i>EGFR</i> mutation testing by the fully-automated qPCR-based Idylla on whole slide and biopsy tumor tissue of non-small cell lung cancer.
Authors: Marius Ilie, Simon Heeke, Catherine Butori, Virginie Tanga, Kevin Washetine, Sandra Lassalle, Elodie Long, Priscilla Maitre, Olivier Bordone, Virginie Lespinet, Sylvie Leroy, Jerome Mouroux, Charles Hugo Marquette, Veronique Hofman, Paul Hofman
Journal: Journal of Clinical Oncology (2017)

e20632 Background: The use in routine clinical practice of the EGFR tyrosine kinase inhibitors is limited to patients with advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have known EGFR mutations. Currently, patient care has to respond to several imperatives to make it broadly available to all patients; fast and accurate detection of EGFR mutations by a sensitive and specific standardized cost-effective method, easy-to-implement in settings with limited expertise in molecular diagnostics. The possibility to obtain EGFR testing results in less than few hours in a large number of pathology laboratories is recently guaranteed by the Idylla system. Methods: We evaluated the Idylla system (Biocartis) for the detection of EGFR mutations in archived formalin-fixed paraffin-embedded (FFPE) tumor samples from a series of 18 patients with lung adenocarcinoma and compared these results with those obtained by the Therascreen EGFR Pyro assay (Qiagen)-ISO 15189 accredited laboratory method. The results obtained with the two methods were compared on both whole tumor sections from surgical specimens and on tissue sections from three artificially constructed small biopsies (~1 mm diameter) from the same FFPE blocks. Cost-effectiveness and turnaround time comparison between the two methods was performed. Results: In the first assessment on whole tissue sections, the Idylla and pyrosequencing results had an agreement of 94%. When assessed on biopsy cores, Idylla demonstrated agreement with pyrosequencing in 16 of 18 cases (89%). The Idylla EGFR mutation assay produced results faster (sample to result time was about 180 minutes with about 2 minutes of hands on time) than pyrosequencing (sample to result time about 12 hours). For each patient, the Idylla was more cost-effective than pyrosequencin. Conclusions: The Idylla system showed a good sensitivity and was cost-saving in our setting. Because of the easy workflow, the Idylla system has the potential to expand EGFR testing to more pathology laboratories in a reliable and fast manner.
Abstract 5322: Normal breast tissue 5-hydroxymethylcytosine is enriched at DNA regulatory elements of breast cancer cells
Authors: Owen Michael Wilkins, Kevin C. Johnson, E. Andres Houseman, Jessica E. King, Carmen J. Marsit, Brock C. Christensen
Journal: Cancer Research (2018)

Abstract DNA methylation is an established modulator of gene expression in normal mammalian cells. Emerging evidence suggests that the oxidized 5-methylcytosine (5mC) product, 5-hydroxymethylcytosine (5hmC), has distinct biological functions and its dysregulation may contribute to cancer pathogenesis. While 5hmC levels in normal breast tissue have been shown to be elevated relative to several other tissue types, we lack a complete knowledge of the genomic distribution of 5hmC in breast tissue, as well as its potential biological functions. Here, we determined the genome-wide distribution of 5hmC and 5mC using methylation array data from 18 normal breast tissue samples. To disambiguate 5hmC from 5mC, we performed parallel processing of bisulfite and oxidative-bisulfite treated DNA, followed by statistical estimation of the 5mC and 5hmC proportions. Based on the distribution of 5hmC, we identified genomic loci with consistently elevated levels of 5hmC across normal breast tissues. In addition, we showed 5hmC is enriched within transcriptionally active chromatin in breast myoepithelial cells, marked by H3K4 trimethylation. Conversely, 5hmC was depleted within active promoters (H3K9ac-marked DNA) and transcriptionally inactive chromatin (H3K9me3 and H3K27me3-marked DNA). Importantly, the loci with high 5hmC in normal breast tissue were enriched among regulatory elements, including transcription factor binding sites, in transformed normal-like breast MCF10A cells, as well as in multiple breast cancer cell lines. These findings provide a genome-wide distribution of 5hmC in normal breast tissue. Furthermore, these findings identify DNA-regulatory regions in breast cancer cell lines that show statistical enrichment for those sites with elevated 5hmC in normal breast tissue, suggesting deregulation of 5hmC within these elements may contribute to breast carcinogenesis. Citation Format: Owen Michael Wilkins, Kevin C. Johnson, E. Andres Houseman, Jessica E. King, Carmen J. Marsit, Brock C. Christensen. Normal breast tissue 5-hydroxymethylcytosine is enriched at DNA regulatory elements of breast cancer cells [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 5322.
Association Between Antipsychotic Use and Risk of Acute Myocardial Infarction
Authors: Shuai-TingLin, Cheng-ChungChen, Hin-YeungTsang, Chee-SiongLee, PinchenYang, Kai-DaCheng, Dian-JengLi, Chin-JenWang, Yung-ChiHsieh, Wei-ChengYang
Journal: Circulation (2014)

Background—Antipsychotic medications have been increasingly and more widely prescribed despite continued uncertainty about their association with the incidence of acute myocardial infarction (AMI). Methods and Results—We investigated the risk of AMI associated with antipsychotic treatment in 56 910 patients with schizophrenia, mood disorders, or dementia first hospitalized or visiting an emergency room for AMI in 1999 to 2009. A case-crossover design was used to compare the distributions of antipsychotic exposure for the same patient across 1 to 30 and 91 to 120 days just before the AMI event. Adjustments were made for comedications and outpatient visits. The adjusted odds ratio of AMI risk was 2.52 (95% confidence interval, 2.37–2.68) for any antipsychotics, 2.32 (95% confidence interval, 2.17–2.47) for first-generation antipsychotics, and 2.74 (95% confidence interval, 2.49–3.02) for second-generation antipsychotics. The risk significantly increased (P<0.001) with elevations in dosage and in short-term ...
Abstract 11945: Indications and Outcomes Following Transvenous Extraction of ICD versus Pacemaker Leads
Authors: Eric W Black-Maier, Sean D Pokorney, Robert K Lewis, Alexander Christian, Ruth A Greenfield, Donald D Hegland, James P Daubert, Jonathan P Piccini
Journal: Circulation (2015)

Introduction: Percutaneous transvenous lead extraction of cardiovascular implantable electronic devices (CIEDs) is increasingly common. Although ICD leads are widely considered to be more difficult to extract than pacemaker leads, there are few direct comparisons. Methods/Results: Using a cohort of 368 consecutive patients undergoing lead extraction (dwell time &gt;1 year) between 2005-2012, we compared baseline characteristics/outcomes in extractions involving pacing versus ICD leads. We defined major adverse events (MAE) as any events/complications that required procedural intervention, transfusion, or that resulted in death or serious harm during index hospitalization. Median age was 60.6 yrs and 29.6% were women. There were 136 (37%) pacing lead extractions and 232 (63%) ICD lead extractions. Pacing leads had a longer dwell time (6.14 yrs [IQR 1.2-10.9 ] versus 4.4 yrs [IQR 1.1-6.4], p&lt;0.001) and higher median LVEF (55% [IQR 35-55] vs. 30% [IQR 20-40], p&lt;0.001) compared with ICD lead patients. Indications for pacing and ICD lead extractions included sepsis/endocarditis (21.3% vs. 24.6%, p=0.48), pocket infection (40.4% vs. 34.9%, p=0.29), and lead failure (15.4% vs. 38.8%, p&lt;0.001). There were no significant differences between pacing and ICD lead extractions in median fluoroscopy time (5.5 vs. 8.5 minutes, p=0.86) or femoral bailout rate (4.4% vs. 5.2%, p=0.73). There were similar rates of all-cause MAE during index hospitalization (5.1% vs. 5.6%), death (2.2% vs 3.2%) and clinical success (97.0% vs. 97.0%, p=0.55) in pacemaker and ICD extractions, respectively. Conclusions: ICD leads are more commonly extracted relative to pacemaker leads, and this difference is driven by larger numbers of lead failure within ICD leads. Despite much longer dwell times, major adverse events were similar in pacing lead cases compared with ICD extractions.
Abstract 346: Involvement of Non-canonical Wnt-PKC-JNK Pathway in Angiogenesis Enhanced by MSC Overexpressing Wnt11
Authors: MeifengXu, JingcaiWang, BinYu
Journal: Circulation Research (2014)

Wnt11 is a key regulator of cardiac muscle cell proliferation and differentiation during heart development. Here, we hypothesized that preprogramming mesenchymal stem cells (MSC) with Wnt11 enhanced angiogenesis in ischemic myocardium. Methods and Results: An acute myocardial infarction model in SD rats was developed by ligation of the left anterior descending (LAD) coronary artery. Rat bone marrow derived MSC were transduced with Wnt11 gene (MSC-Wnt11) and transplanted into ischemic border area. The animals treated with MSC-Wnt11 showed a significantly improved cardiac function. Furthermore, fluorescent microsphere and histological studies revealed an increased blood flow and blood vessel density in MSC-Wnt11 transplanted animals. In vitro studies using conditioned medium (CdM) obtained from MSC-Wnt11 (CdM-Wnt11) showed an increased the length and number of capillary-like structure (CLS) formation and promoted migration of human umbilical vein endothelial cells (HUVECs), which was similar to that HUVECs ...
Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial
Authors: Patrick M O'Neil, Andreas L Birkenfeld, Barbara McGowan, Ofri Mosenzon, Sue D Pedersen, Sean Wharton, Charlotte Giwercman Carson, Cecilie Heerdegen Jepsen, Maria Kabisch, John P H Wilding
Journal: The Lancet (2018)
Relation Between Work and Labile Phosphate Content in the Isolated Dog Heart
Authors: Albertwollenberger
Journal: Circulation Research (1957)

Starling heart-lung preparations of the dog (with only minor differences in heart rate) were subjected to changes in work load to study their effect on the amount of labile phosphate in the left ventricle. While increasing the work load three to fourfold by increasing output caused no change, doubling the work load by increasing the resistance was accompanied by a marked reduction in labile phosphate. The data suggest that the heart expends phosphate bond energy chiefly in overcoming resistance rather than in systolic emptying.
Short QT Syndrome
Authors: FiorenzoGaita, CarlaGiustetto, FrancescaBianchi, ChristianWolpert, RainerSchimpf, RiccardoRiccardi, StefanoGrossi, ElenaRichiardi, MartinBorggrefe
Journal: Circulation (2003)

Background— A prolonged QT interval is associated with a risk for life-threatening events. However, little is known about prognostic implications of the reverse—a short QT interval. Several members of 2 different families were referred for syncope, palpitations, and resuscitated cardiac arrest in the presence of a positive family history for sudden cardiac death. Autopsy did not reveal any structural heart disease. All patients had a constantly and uniformly short QT interval at ECG. Methods and Results— Six patients from both families were submitted to extensive noninvasive and invasive work-up, including serial resting ECGs, echocardiogram, cardiac MRI, exercise testing, Holter ECG, and signal-averaged ECG. Four of 6 patients underwent electrophysiological evaluation including programmed ventricular stimulation. In all subjects, a structural heart disease was excluded. At baseline ECG, all patients exhibited a QT interval ≤280 ms (QTc ≤300 ms). During electrophysiological study, short atrial and ventric...
Abstract 3866: A novel assay for rapid identification and isolation of single intact circulating tumor cells
Authors: Lili Huang, Le Shen, Min Yu, Paul Liu
Journal: Cancer Research (2018)

Abstract We present a magnetic bead assay for rapid identification and isolation of single intact circulating tumor cells (CTCs). Cell viability is essential for cell culture and downstream molecular analysis. Many CTC isolation technologies, including CellSearch, uses fixation and fluorescent imaging for CTC detection that the captured CTCs are no longer viable. This novel assay utilize magnetic sensing for CTC identification, and therefore preserve CTC integrity and viability. The assay is performed on a microelectronic chip which also generates spatially-patterned microscopic magnetic field to sort single CTCs. We evaluated the performance metrics of the assay with EGFP-expression breast cancer patient derived CTC cells mixed with peripheral blood mononuclear cells (PBMCs) in vitro. Cell suspensions were mixed with magnetic microbeads coated with anti-EpCAM antibodies and then isolated with a magnet. Different amount (20, 50, 100, 500) of CTCs from serial dilution were spiked into 5x10^6 human PBMCs labelled with Alexa Flour 488 anti-human CD45 antibodies. After the assay, no PBMCs are visible which shows high purity in recovered CTCs. Recovery rate, defined by the ratio of the mean of the recovered CTC count to the mean of the spiked CTC count, is in the range of 87% to 92% for the various CTC spiked-in amount. In each spiking experiment, triplicate measurement and controls are used. Total assay time is less than 80 minutes. Conclusion: A rapid assay for isolation and detection of CTCs from PBMCs is demonstrated which shows high recovery rate and viability. This novel assay has great potential for single intact rare cell isolation. Citation Format: Lili Huang, Le Shen, Min Yu, Paul Liu. A novel assay for rapid identification and isolation of single intact circulating tumor cells [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 3866.