tbuckley/cabot-search huggingface dataset:
NCCN Guidelines Insights: Colorectal Cancer Screening, Version 1.2018
Authors: Dawn Provenzale, Samir Gupta, Dennis J. Ahnen, Arnold J. Markowitz, Daniel C. Chung, Robert J. Mayer, Scott E. Regenbogen, Amie M. Blanco, Travis Bray, Gregory Cooper, Dayna S. Early, James M. Ford, Francis M. Giardiello, William Grady, Michael J. Hall, Amy L. Halverson, Stanley R. Hamilton, Heather Hampel, Jason B. Klapman, David W. Larson, Audrey J. Lazenby, Xavier Llor, Patrick M. Lynch, June Mikkelson, Reid M. Ness, Thomas P. Slavin, Shajanpeter Sugandha, Jennifer M. Weiss, Mary A. Dwyer, Ndiya Ogba
Journal: Journal of the National Comprehensive Cancer Network (2018)

The NCCN Guidelines for Colorectal Cancer (CRC) Screening outline various screening modalities as well as recommended screening strategies for individuals at average or increased-risk of developing sporadic CRC. The NCCN panel meets at least annually to review comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize 2018 updates to the NCCN Guidelines, with a primary focus on modalities used to screen individuals at average-risk for CRC.
Abstract 14474: Effect of Statin Therapy on Weight Loss and Diabetes in Bariatric Patients
Authors: Beth ATaylor, JanetNg, AndreaStone, Darren STishler, PavlosPapasavos, Paul DThompson
Journal: Circulation (2016)

Introduction: Bariatric surgeries are considered effective treatments to achieve weight loss and improve diabetes control. Statins increase diabetes onset in clinical trials and many bariatric patients with metabolic disease are treated with statin therapy. Hypothesis: We hypothesized that preoperative statin therapy would reduce the favorable effects of bariatric surgery on diabetes remission and weight loss. Methods: We retrospectively examined the relationship of statin therapy to weight loss, diabetes mellitus onset and remission, and metabolic outcomes after bariatric surgery. The 1575 patients (1231 women) underwent laparoscopic adjustable gastric banding or LAGB (n=1035), Roux-en-Y gastric bypass or RYGB (n=468), and sleeve gastrectomies or SG (n=72) and were categorized as to statin use (n=671) and diabetes status (n=557) preoperatively and at one year follow-up. Results: Diabetes resolved after surgery in 159 or 23.7% of patients on preoperative statins whereas 3 had new onset. Diabetes resolved ...
Abstract 3308: Urine epigenetic biomarkers for NSCLC diagnosis
Authors: Lane Lerner, Lily Zheng, Anastasia Kottorou, Chen Chen, Tomoaki Ito, Kristen Rodgers, Beverly Lee, Robert Winn, Enrico Benedetti, Tza- Huei Wang, Malcolm V. Brock, James G. Herman, Alicia Hulbert
Journal: Cancer Research (2018)

Abstract Purpose: The National Lung Cancer Screening Trial showed mortality reduction on patients with NSCLC by the use of Low-dose CT screening. The study exhibits an unreasonably high false positive rate of 96.6%, which can to lead to significant morbidity and mortality from unnecessary tests. This study aim to determine if methylated promoter regions of a panel of genes that are correlated with Non-Small Cell Lung Cancer can be detected in urine from patients with lung cancer versus those without. Materials and Methods: We conducted a prospective case-control study recruiting subjects from the Lung Cancer Spore Trial. Urine and pre-operative CT scans were obtained from all patients. We processed the urine using the Methylation on Beads assay to isolate and bisulfite treat circulating DNA and then employed Quantitative Methylation Specific Real-Time PCR to detect promoter methylation status of the genes: CDO1, TAC1, HOXA7, HOXA9, SOX17 and ZFP42. Sensitivity, specificity, PPV and NPV values were calculated for each gene methylation status. Results: 34 patients were studied, including 23 patients with NSCLC and 11 patients with benign non-cancerous lesions. The sensitivity, specificity, PPV and NPV values for lung cancer detection in urine are shown in Table 1. Sensitivities ranged 43-96%, Specificities 64-91%, PPV 71-100% and NPV 40-67%. Promoter methylation of the gene panel CDO1, TAC1, HOXA7, HOXA9, SOX17 and ZPF42 has a 78% sensitivity, 91% specificity, 95% PPV and 67% NPV for lung cancer detection. Conclusion: Our study suggests that urine can provide a highly sensitive and specific non-invasive route for lung cancer detection. These results are very promising and could potentially reduce unnecessary morbidity and mortality in people undergoing screening for NSCLC by use of a non-invasive method that could be more accessible on primary care centers. However, further studies and validation with larger sample sizes and different populations are necessary before its application to clinical practice. Patients with positive gene methylation from urine samples and its accuracy for NSCLC detection.Cancer (n=23)Cancer (n=23)Control (n=11)Control (n=11)nSensitivitynSpecificityPPVNPVCDO114611919353TAC11565010010058SOX1716704648050HOXA711483737940HOXA910431919143ZPF4222969187167Panel of genes18781919567 Citation Format: Lane Lerner, Lily Zheng, Anastasia Kottorou, Chen Chen, Tomoaki Ito, Kristen Rodgers, Beverly Lee, Robert Winn, Enrico Benedetti, Tza- Huei Wang, Malcolm V. Brock, James G. Herman, Alicia Hulbert. Urine epigenetic biomarkers for NSCLC diagnosis [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 3308.
Abstract 17064: The Accuracy of an Impedance Cardiogram Based Compression Rate Feedback Algorithm Versus Real-time Video Recording of Chest Compression Rate
Authors: Rebecca Di Maio, Paul Crawford, Olibhear McAlister, Hannah McReynolds, Eddie Clutton, Jennifer Adgey
Journal: Circulation (2015)

Objective: It is widely known that CPR administered in all settings may be sub-optimal. CPR feedback tools can provide reliable feedback to operators to improve compression rate, depth and fraction. The purpose of this study was to evaluate the use of a CPR rate feedback algorithm incorporated into an automated external defibrillator by comparing the CPR compression rate measured by an Impedance Cardiogram based feedback device, a video recording of real-time CPR and using a commercially available accelerometer Hypothesis: ICG based CPR feedback is as effective as accelerometer based feedback. Methods: A total of twelve porcine models were used each weighing 29.62±4.2kg. Rate (CPM), End-tidal CO 2 (ETCO 2 ), Blood Pressure (BP), SpO2 (%) and Depth (mm) was measured for each model. The Impedance Cardiogram (ICG)/Thoracic Impedance was recorded via 2 standard defibrillation electrodes and as a method of detecting the presence of CPR. Ethical approval was granted by the Northern Ireland Home Office and the Home Office in Scotland. Models were anaesthetised using Propofol and Isoflurane and connected to a Datex Ohmeda ® monitor for anaesthesia monitoring. A number of physiological measurements were taken every 2 minutes via the carotid and jugular. Rate and depth were measured continuously using Q-CPR ® , Philips. Recordings from each experiment were acquired using Datex Ohmeda review software for further statistical analysis using SAS 9.2 ® . Findings: The proportion of correct audio and visual feedback of the Impedance Cardiogram based feedback device versus the actual CPR compression rate as demonstrated in video recordings was 95.2%. The study also showed that the proportion of “correct” audio and visual feedback of the SAM 450P CPR Rate Feedback algorithm versus the accelerometer rate (CPM) was 87.5% due to underestimation of some measures in the non-ICG based device. Conclusions: Therefore it could be concluded that an Impedance Cardiogram based feedback device is highly sensitive to end user chest compression rate over a wide range of rates (40 to 180 compressions-per-minute).
Crizotinib in patients (pts) with MET-amplified non-small cell lung cancer (NSCLC): Updated safety and efficacy findings from a phase 1 trial.
Authors: D. Ross Camidge, Gregory Alan Otterson, Jeffrey W. Clark, Sai-Hong Ignatius Ou, Jared Weiss, Steven Ades, Umberto Conte, Yiyun Tang, Sherry Chia-E Wang, Danielle Murphy, Keith D. Wilner, Liza Cosca Villaruz
Journal: Journal of Clinical Oncology (2018)

9062 Background: MET amplification (amp) has been reported in a subset of NSCLC with the frequency varying depending on the definition used. Crizotinib, an ALK/ROS1/MET inhibitor approved in ALK- or ROS1-positive NSCLC, also has proven clinical activity in cases of MET exon 14 alterations and MET amp. Here we present an updated analysis of crizotinib in pts with low, medium (med), and high (hi) levels of MET amp in advanced NSCLC. Methods: In this ongoing, open-label, multicenter, phase 1 trial (NCT00585195), MET amp was locally tested; pts with MET/CEP7 ratios ≥1.8 were eligible. Pts received crizotinib 250 mg BID and were assigned to categories based on low (≥1.8–≤2.2), med ( > 2.2– < 5), or hi (≥5) MET/CEP7 ratios. The latter 2 thresholds were revised to > 2.2– < 4 and ≥4; data were then reanalyzed to better delineate predictive biomarkers of response. Selected endpoints included best overall response (BOR) per RECIST v1.0, time to tumor response (TTR), progression-free survival (PFS), duration of response (DOR) and safety. Results: At data cutoff (31 Oct 2017), 40 pts were treated; 3 had no MET amp. Baseline characteristics were comparable among the revised amp categories. Median TTR was 8.0 wk (range, 7.1–9.1). BOR, DOR, and PFS are shown in the. 3 MET hi pts remain on treatment. The adverse event profile in this cohort was consistent with the established safety profile of crizotinib. Conclusions: Pts with NSCLC with hi MET amp (MET/CEP7 ≥4) showed clinically meaningful antitumor activity with rapid and durable responses. Crizotinib was generally well tolerated. Coincidence with MET exon 14 alterations and other targets of crizotinib is being explored. Clinical trial information: NCT00585195.MET/CEP7 Category Low (N =3) Med (N =14) Hi (N =20) Response evaluable n = 3 n = 14 n = 20 Objective response rate, %a (95% CI) 33.3 (0.8, 90.6) 14.3 (1.8, 42.8) 40.0 (19.1, 63.9) Complete response, n 0 0 2 Partial response, n 1 2 6 Stable disease, n 0 4 6 Progressive disease (PD), n 1 4 3 Early death, n 1 3 1 Indeterminate, n 0 1 2 Median DOR, mo (range)b 12.1 (12.1–12.1) 3.7 (3.7–3.7) 5.5 (3.3–25.8) Median PFS, mo (95% CI)c 1.8 (0.8, 14.0) 1.9 (1.3, 5.5) 6.7 (3.4, 7.4) aResponse-evaluable populationbObjective responderscBased on Kaplan-Meier method
Prevention of Ebola virus disease through vaccination: where we are in 2018
Authors: Yves Lévy, Clifford Lane, Peter Piot, Abdul Habib Beavogui, Mark Kieh, Bailah Leigh, Seydou Doumbia, Eric D'Ortenzio, Claire Lévy-Marchal, Jerome Pierson, Deborah Watson-Jones, Vinh-Kim Nguyen, Heidi Larson, Julia Lysander, Christine Lacabaratz, Rodolphe Thiebaut, Augustin Augier, David Ishola, Stephen Kennedy, Geneviève Chêne, Brian Greenwood, James Neaton, Yazdan Yazdanpanah
Journal: The Lancet (2018)
Angiotensin II Potentiates Vascular Endothelial Growth Factor–Induced Angiogenic Activity in Retinal Microcapillary Endothelial Cells
Authors: AtsushiOtani, HitoshiTakagi, KiyoshiSuzuma, YoshihitoHonda
Journal: Circulation Research (1998)

Abstract—Angiotensin II (Ang II) plays a role in the development of many vascular diseases. In the present study, we have investigated the effect of Ang II on vascular endothelial growth factor (VEGF) receptor expression and VEGF-induced angiogenic activity in bovine retinal microcapillary endothelial cells (BRECs). Ang II induced a significant increase of kinase domain–containing receptor/total liver kinase (KDR/Flk-1) mRNA in a time- and dose-dependent manner, with a maximal 4.3±0.8-fold increase after a 4-hour stimulation. Ang II increased the rate of KDR gene transcription by 5.4-fold, whereas the half-life of KDR mRNA was not increased significantly. The increase depended partially on new protein synthesis. The Ang II–induced KDR mRNA increase was inhibited by either [Sar1,Ile8]angiotensin or angiotensin type 1 receptor antagonists but was not significantly altered by angiotensin type 2 receptor antagonists. The PKC inhibitor reduced Ang II–induced KDR mRNA expression by 70±15%. The tyrosine kinase i...
Abstract 20572: Exercise-Mediated Wall Shear Stress Induces Mitochondrial Remodeling and Prevents Angiotensin II-Induced High Blood Pressure
Authors: Boa Kim, Brittany Wilson, Steven J Forrester, Ji-Seok Kim, Keisuke Kawata, Hojun Lee, Mayra C Santiago, Michael D Brown, Satoru Eguchi, Joon-Young Park
Journal: Circulation (2014)

Objective: Regular practice of exercise is one of the most effective non-pharmacological interventions that improve vascular health, which is thought to be mediated by a repeated exposure of vessel...
Abstract 4273: Identification of RNA-seq shape abnormality
Authors: Hyo Young Choi, David N. Hayes, James S. Marron
Journal: Cancer Research (2018)

Abstract A substantial proportion of human genes differ in function through different forms of shape changes in read coverage of RNA-seq. For example, tumor-suppressor genes lose their function through various changes in expression such as aberrant splicing, frameshift indel, large deletions, or overexpression of noncoding RNAs. Although previous studies have examined mutational effect on such shape changes, it has been observed that a large fraction of shape aberration occurs in the absence of mutations. We hypothesize that read coverage shapes would show rich information on various forms of abnormality in RNA-seq data, which may have been missed in current mutation callers. We have developed a statistical method to systematically detect abnormal RNA-seq samples using read coverage data alone independently of mutational analysis. We model the underlying mechanism possibly generating aberrant shapes by multiple unknown mixture distributions, recasting the problem as high-dimensional latent variables framework. Based on this underlying mechanism, we normalize the read coverage to adjust different library sizes, extract the latent information in a robust way, and determine the cases that are strongly involved in abnormality. This approach allows us to detect not only local changes in expression such as alternative splicing events and frameshift indel but also landscape changes such as fusion and a wide range of deletions. This methodology can be applied genome-widely to detect key genes with strong shape aberrations, prioritizing genes for further investigation. We analyzed 522 TCGA head and neck squamous cell carcinomas RNA-seq tumor samples. At several known tumor-suppressor genes, we identified the cases with novel structural changes including alternative splicing, intragenic deletion, and fusion with/without mutations reported as well as the cases with no evidence of changes despite presence of mutations known for altering shapes. Notably, some of the identified shape changes in TP53 and CDKN2A were confirmed as being the outcomes of missing genetic variants near splice sites (exon-intron junctions). The genome-wide study with carefully chosen significance level provided a set of key genes with strong evidence of shape abnormality including TP53, CDKN2A, and FAT1 that are known for the most alternative splicing events. We also analyzed how often such shape changes arise with or without certain mutations in genome-wide scans. To conclude, our results provide a new statistical framework for various forms of RNA-seq shape changes and a tool for systematic discovery of such abnormal samples, and give insights into mutational effect on shape aberration. Citation Format: Hyo Young Choi, David N. Hayes, James S. Marron. Identification of RNA-seq shape abnormality [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 4273.
Jujuboside A promotes Aβ clearance and ameliorates cognitive deficiency in Alzheimer's disease through activating Axl/HSP90/PPARγ pathway
Authors: Mu Zhang, Cheng Qian, Zu-Guo Zheng, Fei Qian, Yanyan Wang, Pyone Myat Thu, Xin Zhang, Yaping Zhou, Lifan Tu, Qingling Liu, Hui-Jun Li, Hua Yang, Ping Li, Xiaojun Xu
Journal: Theranostics (2018)

Rationale: It has been reported that peroxisome proliferator activated receptor γ (PPARγ) level decreases significantly in the brains of Alzheimer's disease (AD) patients and mice models, while the mechanism is unclear.This study aims to unravel the mechanism that amyloid β (Aβ) decreases PPARγ and attempted to discover lead compound that preserves PPARγ. Methods:In APP/PS1 transgenic mice and Aβ treated microglia, the interaction between HSP90 and PPARγ were analyzed by western blot.Using a PPRE (PPARγ responsive element) containing reporter cell line, compounds that activate PPARγ activity were identified.After genetic ablation or pharmacological inhibition of potential target pathways, the target of jujuboside A (JuA) was discovered through Axl/HSP90β.After oral administration or intrathecal injection, the anti-AD activity of JuA was evaluated by Morris water maze (MWM) test and object recognition test.Soluble Aβ42 levels and plaque numbers after JuA treatment were detected by thioflavin S staining, and the activation of microglia was assayed by immunofluorescence staining against Iba-1. Results:We found that Aβ stress decreased heat shock protein 90 β (HSP90β), subsequently reduced the abundance of PPARγ, and down-regulated Aβ clearance-related genes in BV2 cells and primary microglia.We identified that JuA stimulated the expression of HSP90β, strengthened the interaction between HSP90β and PPARγ, preserved PPARγ levels, and thus effectively promoted the clearance of Aβ42.We demonstrated that JuA increased HSP90β expression through Axl/ERK pathway.JuA significantly ameliorated cognitive deficiency in APP/PS1 transgenic mice, meanwhile, JuA significantly reduced the soluble Aβ42 levels and plaque numbers in the brain.Notably, the therapeutic effects of JuA were dampened by R428, an Axl inhibitor. Conclusions:This study suggests that the up-regulation of HSP90β by JuA through Axl is a potential therapeutic strategy to facilitate Aβ42 clearance and ameliorate cognitive deficiency in AD.
Endothelium-Dependent Relaxation of Collateral Microvessels After Intramuscular Gene Transfer of Vascular Endothelial Growth Factor in a Rat Model of Hindlimb Ischemia
Authors: SatoshiTakeshita, TakaakiIsshiki, MasahikoOchiai, KojiEto, HidezoMori, EtsuroTanaka, KeijiUmetani, TomohideSato
Journal: Circulation (1998)

Background—Recent investigations have demonstrated the ability of vascular endothelial growth factor (VEGF) to augment the development of collateral arteries in vivo. In vitro studies have suggested that the use of VEGF also improves the endothelium-dependent relaxation of collaterals at the microvascular level. The purpose of this study was to determine in vivo the extent to which vasomotor responses of collateral microvessels are altered after VEGF treatment. Methods and Results—Ischemia was induced in the hindlimb of 35 rats by excision of the femoral artery. Immediately thereafter, 400 μg of a plasmid encoding VEGF or β-galactosidase (control) was transfected into limb muscles. Four weeks later, synchrotron radiation microangiography, with a spatial resolution of 30 μm, was performed to document the reactivity of collateral microvessels. Administration of the endothelium-dependent vasodilator acetylcholine failed to induce dilation of collateral microvessels in control animals. By contrast, profound d...
Mechanisms of resistance to trastuzumab as neoadjuvant therapy in women with HER2-overexpressing operable breast cancer.
Authors: Hiromitsu Jinno, Tomomi Sato, Tetsu Hayashida, Maiko Takahashi, Shigemichi Hirose, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2012)

e11060 Background: Despite clinical usefulness of trastuzumab, intrinsic or acquired resistance is a common clinical phenomenon. Potential mechanisms of resistance include aberrant downstream signaling caused by loss of PTEN and/or PIK3CA mutation, alternative signaling from IGF-1R and masking with MUC4. Methods: Patients with operable breast cancer received 12 cycles of weekly paclitaxel (80 mg/m2 IV) plus weekly trastuzumab (4mg/kg loading dose followed by 2 mg/kg IV) before surgery. All tumors were HER2-positive by immunohistochemistry (IHC) or fluorescence in situ hybridization. Expressions of ER, PgR, Ki67, PTEN, phosphorylated IGF-1R (pIGF-1R) and MUC4 were performed by IHC in core needle biopsy samples at baseline. ER and PgR status was assessed using Allred score. For Ki67 labeling index, a total of 400 cells were counted from three consecutive high-power magnifications. PTEN, pIGF-1R and MUC4 expression level was scored semiquantitatively based on staining intensity. PIK3CA mutation status was evaluated by sequencing of PIK3CA exons 9 and 20 using PCR amplification and direct sequencing. Results: Thirty-seven patients were enrolled and assessable for clinical and pathologic responses. The pCR rate was 48.6% (18/37). ER and PgR were positive in 18 (48.6%) and 16 (43.2%) patients, respectively. Negative, moderate and strong membranous expression of MUC4 was observed in 3 (8.1%), 18 (48.6%) and 12 (32.4%) patients, respectively. Membranous staining for pIGF1-R was negative in 24 (64.9%) patients. PTEN loss was observed in 33.3% (8/24) of the tumor examined. PIK3CA sequence analysis of the 13 tumors identified 2 mutations in exon 20 and 2 mutations in exon 9, corresponding to a PIK3CA mutation frequency of 30.8%. MUC4 and pIGF1-R status did not affect the pCR rate. PTEN loss and/or PIK3CA mutation were not significantly associated with pCR rate. pCR rate was significantly correlated with PgR negativity (p=0.004) and higher Ki67 (p=0.01). Conclusions: These data indicate that aberrant downstream signaling caused by loss of PTEN and/or PIK3CA mutation, alternative signaling from IGF-1R and masking with MUC4 were not important mechanisms of resistance to trastuzumab.
Natural History of Rheumatic Aortic Regurgitation
Authors: Mariospagnuolo, Howardkloth, Angelotaranta, Eugeniedoyle, Bernardpasternack
Journal: Circulation (1971)

The medical courses of 174 young patients with aortic regurgitation were followed prospectively for a median of 10 years. The data were analyzed by life-table methods; congestive failure and angina, as well as death, were considered as end points, since the occurrence of the former is considered sufficient indication for aortic valve replacement. Thirty-one patients developed the triad of moderate or marked left ventricular enlargement, two or three electrocardiographic abnormalities, and abnormal blood pressure. Thirty-three percent of these patients either died or had failure or angina within 1 year, 48% within 2 years, 65% within 3 years, and 87% within 6 years from the acquisition of the triad. The 71 patients with none of the above features had uneventful courses. Of the 71 patients with one or two features only seven either died (three) or became symptomatic. These data are useful for patient selection for surgery before symptoms appear.