tbuckley/cabot-search huggingface dataset:
P535Identification of specific profiles of small non-coding RNAs derived from microvesicles of CTEPH patients
Authors: C Lipps, P Northe, R Figueiredo, M Rohde, C Liebetrau, T Keller, O Doerr, H M Nef, C W Hamm, C Troidl
Journal: Cardiovascular Research (2018)

enhanced cholesterol efflux capacity and may underline the improved HDL functionality after RYGB.Reduced sphingosine-1-phosphate (S1P) content is a known mediator of HDL dysfunction.Indeed, S1P content was also increased in small HDL-1Y after RYGB.Total HDL cholesterol concentration was increased post RYGB.Conclusions: Small HDL-1Y after RYGB are increased and have enhanced cholesterol efflux capacity.Elevated content in PC, PS, PA and their lyso-forms as well as increased S1P levels may contribute to the improved athero-protective function of small HDL-1Y after RYGB.RYGB seems to achieve a dual benefit increasing the concentration and function of HDL.
DNA Repair Deficiency and Immunotherapy Response
Authors: Kent W. Mouw, Alan D. D’Andrea
Journal: Journal of Clinical Oncology (2018)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Alterations in DNA Damage Response and Repair Genes as Potential Marker of Clinical Benefit From PD-1/PD-L1 Blockade in Advanced Urothelial Cancers. February 28, 2018 ARTICLE CITATION DOI: 10.1200/JCO.2018.78.2425 Journal of Clinical Oncology - published online before print April 23, 2018 PMID: 29683789 DNA Repair Deficiency and Immunotherapy Response Kent W. MouwxKent W. MouwSearch for articles by this author and Alan D. D'AndreaxAlan D. D'AndreaSearch for articles by this author Show More Kent W. Mouw, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston, MA; and Alan D. D'Andrea, Dana-Farber Cancer Institute, Boston, MA https://doi.org/10.1200/JCO.2018.78.2425 First Page Full Text PDF Figures and Tables © 2018 by American Society of Clinical Oncology Companion Alterations in DNA Damage Response and Repair Genes as Potential Marker of Clinical Benefit From PD-1/PD-L1 Blockade in Advanced Urothelial Cancers
Abstract 13847: Impact of the Unzipping Technique on Pulmonary Artery Structure and Growth
Authors: Luke Lamers, Cole Nygard, Rachel Luehrs, Alejandro Roldan, Melissa Bates
Journal: Circulation (2016)

Introduction: With the unzipping technique, small diameter stents are implanted to relieve pulmonary artery (PA) stenosis, subsequently dilated, fractured and re-stented with large stents dilatable to adult PA diameters. The unzipping technique is utilized in clinical practice with undefined long term results. This study assessed the impact of unzipping on PA structure and growth. Methods: Twelve piglets with left PA (LPA) stenosis underwent the unzipping sequence at 6, 10 and 18 weeks of age and were compared to normal controls and controls with untreated LPA stenosis. 2D and 3D rotational angiography pre/post interventions and PA histology was performed on all animals. Results: Eleven of twelve animals completed the three catheterizations. One stent (4 mm implant diameter) could not be crossed at the second procedure. Following the interventions, the diameter of the unzipped LPA was similar to the proximal LPA of normal controls (14 mm ± 1.2 vs 14.7 mm ± 1, p = 0.19). The diameter of the distal LPA was larger in normal controls, compared to interventions and controls with untreated LPA stenosis (14.6 mm ± 0.9 vs 11.6 mm ± 1.9, vs 10 mm ± 1.2, p &lt; .01). Diameters of six 1 st order LPA branches were similar between normal controls and interventions, and larger than the branch diameters in the stenosis controls. Right PA (RPA) dimensions were larger in controls with untreated stenosis, compared to normal controls and interventions (17.8 mm ± 1.2 vs 16.2 mm ± .9 vs 16 ± 1.7 mm p&lt;0.05). RPA 1 st order branching diameters were similar for normal controls and interventions. RPA 1 st order branch diameters in stenosis controls were larger for 3 of 6 branches compared to normal controls and 1 of 6 compared to interventions. Histologically, the distal LPA displayed uniform fibrointimal proliferation and smooth muscle hypertrophy in pigs with both interventions and untreated stenosis. Focal RPA fibrointimal proliferation was noted in stenosis and intervention animals. Conclusion: PA growth distal to the unzipped segment is partially compromised, yet 1 st order branch diameters are normal and significantly larger, compared to untreated stenosis. Histological vascular abnormalities are noted bilaterally in stenosis animals which do not normalize following the unzipping technique.
P326New signaling pathways potentially involved in human mitral valve prolapse
Authors: P Songia, V Myasoedova, P Gripari, V Valerio, L Fusini, L Cavallotti, G Tamborini, M Pepi, P Poggio
Journal: Cardiovascular Research (2018)

genotype-phenotype correlation in large families.Our data highlights the importance of AC cascade genetic screening to determine the clinical significance of rare genetic variants.
Comment on Chan et al. FGF23 Concentration and <i>APOL1</i> Genotype Are Novel Predictors of Mortality in African Americans With Type 2 Diabetes. Diabetes Care 2018;41:178–186
Authors: Ying Zheng, Zhen Wang
Journal: Diabetes Care (2018)

We read with great interest the article by Chan et al. (1) demonstrating that fibroblast growth factor 23 (FGF23) concentration is a novel predictor of mortality in African Americans with type 2 diabetes. FGF23 is the main hormone mediating serum phosphorus concentration through inhibiting tubular reabsorption of phosphorus from the urine (2). Meanwhile, serum phosphorus is the main stimulus for FGF23 secretion. In progressive chronic kidney disease …
Blockade of Myeloid-Derived Suppressor Cell Expansion with All-<i>Trans</i> Retinoic Acid Increases the Efficacy of Antiangiogenic Therapy
Authors: Raimund Bauer, Florian Udonta, Mark Wroblewski, Isabel Ben-Batalla, Ines Miranda Santos, Federico Taverna, Meike Kuhlencord, Victoria Gensch, Sarina Päsler, Stefan Vinckier, Johanna M. Brandner, Klaus Pantel, Carsten Bokemeyer, Thomas Vogl, Johannes Roth, Peter Carmeliet, Sonja Loges
Journal: Cancer Research (2018)

Intrinsic and adaptive resistance hampers the success of antiangiogenic therapies (AAT), especially in breast cancer where this treatment modality has proven largely ineffective. Therefore, novel strategies to improve the efficacy of AAT are warranted. Solid tumors such as breast cancer are characterized by a high infiltration of myeloid-derived suppressor cells (MDSC), which are key drivers of resistance to AAT. Therefore, we hypothesized that all-trans retinoic acid (ATRA), which induces differentiation of MDSC into mature cells, could improve the therapeutic effect of AAT. ATRA increased the efficacy of anti-VEGFR2 antibodies alone and in combination with chemotherapy in preclinical breast cancer models. ATRA reverted the anti-VEGFR2-induced accumulation of intratumoral MDSC, alleviated hypoxia, and counteracted the disorganization of tumor microvessels. Mechanistic studies indicate that ATRA treatment blocked the AAT-induced expansion of MDSC secreting high levels of vessel-destabilizing S100A8. Thus, concomitant treatment with ATRA holds the potential to improve AAT in breast cancer and possibly other tumor types.Significance: Increasing the therapeutic efficiency of antiangiogenic drugs by reducing resistance-conferring myeloid-derived suppressor cells might improve breast cancer treatment.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/12/3220/F1.large.jpg Cancer Res; 78(12); 3220-32. ©2018 AACR.
Real life efficacy of ledipasvir/sofosbuvir in hepatitis C genotype 4–infected patients with advanced liver fibrosis and decompensated cirrhosis
Authors: Faisal M. Sanai, Ibrahim H. Altraif, Khalid Alswat, Adnan AlZanbagi, Mohamed A. Babatin, Abdallah AlMousa, Nawaf H Almutairi, Mohammed S. Aljawad, Abdullah S. Alghamdi, Abdulrahman A. Aljumah, Abduljaleel M. Alalwan, Waleed K. Al-Hamoudi, Abdullah M. Assiri, Yaser Dahlan, Ashwaq Alsahafi, Hammad S. Alothmani, Mohammed S. AlSaleemi, Waleed A. Mousa, Ali Albenmousa, Abdelrahman Awny, Haziz Albiladi, Ayman A. Abdo, Hamdan AlGhamdi
Journal: Journal of Infection (2018)
Unicentric Castleman’s Disease Revealed by 18F-FDG PET/CT and Somatostatin Receptor Scintigraphy With 99mTc-HYNIC-TOC
Authors: Yaping Luo, Ling Wang, Qingqing Pan, Yanru Ma, Fang Li
Journal: Clinical Nuclear Medicine (2018)

A 51-year-old woman with a history of hypertension and abdominal pain was found with a retroperitoneal mass. The mass had intense enhancement in contrast-enhanced CT, and it showed a moderate degree of increased FDG uptake in PET/CT. The mass was also positive in somatostatin receptor scintigraphy with Tc-HYNIC-TOC, but it was negative in I-MIBG scan. The histopathological result after surgical resection of the mass confirmed the diagnosis of Castleman's disease, the hyaline vascular variant.
Notch-effector CSL promotes squamous cell carcinoma by repressing histone demethylase KDM6B
Authors: Dania Al Labban, Seung-Hee Jo, Paola Ostano, Chiara Saglietti, Massimo Bongiovanni, Renato Panizzon, G. Paolo Dotto
Journal: Journal of Clinical Investigation (2018)

Notch 1/2 genes play tumor-suppressing functions in squamous cell carcinoma (SCC), a very common malignancy in skin and internal organs. In contrast with Notch, we show that the transcription factor CSL (also known as RBP-Jκ), a key effector of canonical Notch signaling endowed with intrinsic transcription-repressive functions, plays a tumor-promoting function in SCC development. Expression of this gene decreased in upper epidermal layers and human keratinocytes (HKCs) undergoing differentiation, while it increased in premalignant and malignant SCC lesions from skin, head/neck, and lung. Increased CSL levels enhanced the proliferative potential of HKCs and SCC cells, while silencing of CSL induced growth arrest and apoptosis. In vivo, SCC cells with increased CSL levels gave rise to rapidly expanding tumors, while cells with silenced CSL formed smaller and more differentiated tumors with enhanced inflammatory infiltrate. Global transcriptomic analysis of HKCs and SCC cells with silenced CSL revealed major modulation of apoptotic, cell-cycle, and proinflammatory genes. We also show that the histone demethylase KDM6B is a direct CSL-negative target, with inverse roles of CSL in HKC and SCC proliferative capacity, tumorigenesis, and tumor-associated inflammatory reaction. CSL/KDM6B protein expression could be used as a biomarker of SCC development and indicator of cancer treatment.
Testing Ashkenazi Jewish Women for Mutations Predisposing to Breast Cancer in Genes Other Than <i>BRCA1</i> and <i>BRCA2</i>—Reply
Authors: Mary-Claire King, Tom Walsh
Journal: JAMA Oncology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Biomarker‐based phenotyping of myocardial fibrosis identifies patients with heart failure with preserved ejection fraction resistant to the beneficial effects of spironolactone: results from the Aldo‐DHF trial
Authors: Susana Ravassa, Tobias Trippel, Doris Bach, Diana Bachran, Arantxa González, Begoña López, Rolf Wachter, Gerd Hasenfuss, Christian Delles, Anna F. Dominiczak, Burkert Pieske, Javier Díez, Frank Edelmann
Journal: European Journal of Heart Failure (2018)
Cervical Pessary and Spontaneous Preterm Birth
Authors: Jim Thornton
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Inhibition of YAP activation induces cell senescence and autophagy while blocking cell proliferation in cholangiocarcinoma (CCA)
Authors: M. Cadamuro, G. Casati, T. Stecca, S. Brivio, C. Milani, V. Mariotti, E. Kaffe, C. Spirli, M. Amenduni, R. Fiorotto, U. Cillo, G. Maria, L. Fabris, M. Strazzabosco
Journal: Journal of Hepatology (2018)
Randomised controlled trial of GM-CSF in critically ill patients with impaired neutrophil phagocytosis
Authors: Emma M Pinder, Anthony J Rostron, Thomas P Hellyer, Marie-Helene Ruchaud-Sparagano, Jonathan Scott, James G Macfarlane, Sarah Wiscombe, John D Widdrington, Alistair I Roy, Vanessa C Linnett, Simon V Baudouin, Stephen E Wright, Thomas Chadwick, Tony Fouweather, Jatinder K Juss, Edwin R Chilvers, Susan A Bowett, Jennie Parker, Daniel F McAuley, Andrew Conway Morris, A John Simpson
Journal: Thorax (2018)

Background Critically ill patients with impaired neutrophil phagocytosis have significantly increased risk of nosocomial infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) improves phagocytosis by neutrophils ex vivo. This study tested the hypothesis that GM-CSF improves neutrophil phagocytosis in critically ill patients in whom phagocytosis is known to be impaired. Methods This was a multicentre, phase IIa randomised, placebo-controlled clinical trial. Using a personalised medicine approach, only critically ill patients with impaired neutrophil phagocytosis were included. Patients were randomised 1:1 to subcutaneous GM-CSF (3 μg/kg/day) or placebo, once daily for 4 days. The primary outcome measure was neutrophil phagocytosis 2 days after initiation of GM-CSF. Secondary outcomes included neutrophil phagocytosis over time, neutrophil functions other than phagocytosis, monocyte HLA-DR expression and safety. Results Thirty-eight patients were recruited from five intensive care units (17 randomised to GM-CSF). Mean neutrophil phagocytosis at day 2 was 57.2% (SD 13.2%) in the GM-CSF group and 49.8% (13.4%) in the placebo group, p=0.73. The proportion of patients with neutrophil phagocytosis≥50% at day 2, and monocyte HLA-DR, appeared significantly higher in the GM-CSF group. Neutrophil functions other than phagocytosis did not appear significantly different between the groups. The most common adverse event associated with GM-CSF was fever. Conclusions GM-CSF did not improve mean neutrophil phagocytosis at day 2, but was safe and appeared to increase the proportion of patients with adequate phagocytosis. The study suggests proof of principle for a pharmacological effect on neutrophil function in a subset of critically ill patients.
Preliminary analysis of the Prime Study; A randomized controlled trial comparing the hepatitis C care cascade in primary care vs. tertiary care
Authors: A. Wade, J. Doyle, E. Gane, C. Stedman, B. Draper, D. Iser, S. Roberts, W. Kemp, D. Petrie, N. Scott, P. Higgs, P. Agius, J. Roney, L. Stothers, A. Thompson, M. Hellard
Journal: Journal of Hepatology (2018)
Weighing the risks of valproate in women who could become pregnant
Authors: Heather Angus-Leppan, Rebecca S N Liu
Journal: BMJ (2018)

Despite international consensus on the harmful effects of valproate during pregnancy, women should not be denied the human right to make their own decisions after fully informed discussion, say <b>Heather Angus-Leppan</b> and <b>Rebecca Liu</b>
SCANPY: large-scale single-cell gene expression data analysis
Authors: F. Alexander Wolf, Philipp Angerer, Fabian J. Theis
Journal: Genome biology (2018)

Scanpy is a scalable toolkit for analyzing single-cell gene expression data. It includes methods for preprocessing, visualization, clustering, pseudotime and trajectory inference, differential expression testing, and simulation of gene regulatory networks. Its Python-based implementation efficiently deals with data sets of more than one million cells ( https://github.com/theislab/Scanpy ). Along with Scanpy, we present AnnData, a generic class for handling annotated data matrices ( https://github.com/theislab/anndata ).
TCTAP A-041 Impact of Pulsed Central Pressure and Its Amplification on Coronary Lesions and In-stent Restenosis
Authors: Mohamed Abed Bouraghda, Nazim Megherbi, Said Benghezel, Wathik Takdemt, Redouane Nedjar, Mohamed Chettibi, Mohamed Tahar Chafik Bouafia
Journal: Journal of the American College of Cardiology (2018)
Selective RET kinase inhibition for patients with RET-altered cancers
Authors: V. Subbiah, V. Velcheti, B.B. Tuch, K. Ebata, N.L. Busaidy, M.E. Cabanillas, L.J. Wirth, S. Stock, S. Smith, V. Lauriault, S. Corsi-Travali, D. Henry, M. Burkard, R. Hamor, K. Bouhana, S. Winski, R.D. Wallace, D. Hartley, S. Rhodes, M. Reddy, B.J. Brandhuber, S. Andrews, S.M. Rothenberg, A. Drilon
Journal: Annals of Oncology (2018)

BackgroundAlterations involving the RET kinase are implicated in the pathogenesis of lung, thyroid and other cancers. However, the clinical activity of multikinase inhibitors (MKIs) with anti-RET activity in RET-altered patients appears limited, calling into question the therapeutic potential of targeting RET. LOXO-292 is a selective RET inhibitor designed to inhibit diverse RET fusions, activating mutations and acquired resistance mutations.Patients and methodsPotent anti-RET activity, high selectivity, and central nervous system coverage were confirmed preclinically using a variety of in vitro and in vivo RET-dependent tumor models. Due to clinical urgency, two patients with RET-altered, MKI-resistant cancers were treated with LOXO-292, utilizing rapid dose-titration guided by real-time pharmacokinetic assessments to achieve meaningful clinical exposures safely and rapidly.ResultsLOXO-292 demonstrated potent and selective anti-RET activity preclinically against human cancer cell lines harboring endogenous RET gene alterations; cells engineered to express a KIF5B-RET fusion protein −/+ the RET V804M gatekeeper resistance mutation or the common RET activating mutation M918T; and RET-altered human cancer cell line and patient-derived xenografts, including a patient-derived RET fusion-positive xenograft injected orthotopically into the brain. A patient with RET M918T-mutant medullary thyroid cancer metastatic to the liver and an acquired RET V804M gatekeeper resistance mutation, previously treated with six MKI regimens, experienced rapid reductions in tumor calcitonin, CEA and cell-free DNA, resolution of painful hepatomegaly and tumor-related diarrhea and a confirmed tumor response. A second patient with KIF5B-RET fusion-positive lung cancer, acquired resistance to alectinib and symptomatic brain metastases experienced a dramatic response in the brain, and her symptoms resolved.ConclusionsThese results provide proof-of-concept of the clinical actionability of RET alterations, and identify selective RET inhibition by LOXO-292 as a promising treatment in heavily pretreated, multikinase inhibitor-experienced patients with diverse RET-altered tumors.
Rediagnosis of Lung Cancer as NUT Midline Carcinoma Based on Clues From Tumor Genomic Profiling
Authors: Alexander S. Baras, Jarushka Naidoo, Christine L. Hann, Peter B. Illei, Charles W. Reninger, Josh Lauring
Journal: Journal of the National Comprehensive Cancer Network (2018)

Tumor DNA sequencing can identify rare driver genomic alterations that suggest targets for cancer therapy, even when these drivers cannot be suspected on clinical grounds. In some cases, genomic alterations identified in the tumor can lead to a change in diagnosis with implications for prognosis and therapy. This report describes a case in which evaluation of tumor sequencing results by a molecular tumor board (MTB) led to rediagnosis of a non–small cell lung cancer as highly aggressive NUT midline carcinoma, with implications for targeted therapy using an investigational bromodomain and extraterminal (BET) inhibitor. We discuss the molecular biology and diagnosis of this rare tumor, and suggest how improved annotation of tumor sequencing reports and multidisciplinary expertise of MTBs can facilitate timely diagnosis of rare tumors and application of potential targeted therapies.
TCTAP A-149 Impact of Beta-blocker on Long-term Outcomes After Percutaneous Coronary Intervention for Chronic Total Occlusion: Data from Decision-CTO Registry
Authors: Minsoo Kim, Yong-Hoon Yoon, Sang Yong Om, Hanbit Park, Sang-Cheol Cho, Sangwoo Park, Tae-Oh Kim, Sun Hack Lee, Osung Kwon, Kyusup Lee, Do-Yoon Kang, Jung-Min Ahn, Duk-Woo Park, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2018)