tbuckley/cabot-search huggingface dataset:
Phase Ib Safety, Two-Dose Study of MultiGeneAngio in Patients with Chronic Critical Limb Ischemia
Authors: Moshe Y. Flugelman, Moshe Halak, Boris Yoffe, Jacob Schneiderman, Chen Rubinstein, Allan-Isaac Bloom, Eran Weinmann, Ilya Goldin, Victor Ginzburg, Olga Mayzler, Aaron Hoffman, Belly Koren, Diana Gershtein, Michal Inbar, Marina Hutoran, Adili Tsaba
Journal: Molecular Therapy (2017)

Critical limb ischemia (CLI) is the most severe presentation of peripheral arterial disease. We developed cell-based therapy entailing intra-arterial injection of autologous venous endothelial cells (ECs) modified to express angiopoietin 1, combined with autologous venous smooth muscle cells (SMCs) modified to express vascular endothelial growth factor. This combination promoted arteriogenesis in animal models and was safe in patients with limiting claudication. In an open-label, phase Ib study, we assessed the safety and efficacy of this therapy in CLI patients who failed or were unsuitable for surgery or intravascular intervention. Of 23 patients enrolled, 18 with rest pain or non-healing ulcers (Rutherford categories 4 and 5) were treated according to protocol, and 5 with significant tissue loss (Rutherford 6) were treated under compassionate treatment. Patients were assigned randomly to receive 1 × 107 or 5 × 107 (EC-to-SMC ratio, 1:1) of the cell combination. One-year amputation-free survival rate was 72% (13/18) for Rutherford 4 and 5 patients; all 5 patients with Rutherford 6 underwent amputation. Of the 12 with unhealing ulcers at dosing, 6 had complete healing and 2 others had >66% reduction in ulcer size. Outcomes did not differ between the dose groups. No severe adverse events were observed related to the therapy.
Phase I Trial of the Targeted Alpha-Particle Nano-Generator Actinium-225 (225Ac)-Lintuzumab (Anti-CD33; HuM195) in Acute Myeloid Leukemia (AML)
Authors: Joseph G. Jurcic, Todd L. Rosenblat, Michael R. McDevitt, Neeta Pandit-Taskar, Jorge A. Carrasquillo, Suzanne M. Chanel, Kevin Zikaras, Mark G. Frattini, Peter G. Maslak, Dragan Cicic, Steven M. Larson, David A. Scheinberg
Journal: Blood (2011)
Th17 Cells Blood Proportions Are Influenced by Factors Associated with CRP Serum Level Increase and with NOD2/CARD15 Gene Mutation
Authors: Andrzej Lange, Sylwia Mizia, Jolanta Bochenska, Przemyslaw Czajka, Janusz Lange, Monika Mordak, Dorota Dlubek
Journal: Blood (2012)
Landmark Analyses of DNMT3A Mutations in Hematological Malignancies
Authors: Vera Grossmann, Alexander Kohlmann, Claudia Haferlach, Tamara Alpermann, Melanie Wild, Sandra Weissmann, Christiane Eder, Frank Dicker, Wolfgang Kern, Susanne Schnittger, Torsten Haferlach
Journal: Blood (2011)
Laminin α4 Deficiency Results in Impaired Hematopoietic Recovery Accompanied with Altered Bone Marrow Niche after Myelosuppression
Authors: Makoto Kondo, Pingnan Xiao, Lakshmi Sandhow, Monika Dolinska, Thibault Bouderlique, Anne-Sofie Johansson, Hong Qian
Journal: Blood (2016)
Perifosine, an Oral Bioactive Novel Akt Inhibitor, Induces In Vitro and In Vivo Antitumor Activity in Waldenstrom Macroglobulinemia.
Authors: Xavier Leleu, Xiaoying Jia, Anne-Sophie Moreau, Evdoxia Hatjiharisi, Hai Ngo, Garrett O’Sullivan, Daisy Moreno, Tanyel Kiziltepe, Enrique Ocio, Allen Ho, Thierry Facon, Steven Treon, Teru Hideshima, Kenneth Anderson, Irene Ghobrial
Journal: Blood (2006)
High flow nasal cannula (HFNC) versus nasal continuous positive airway pressure (nCPAP) for the initial respiratory management of acute viral bronchiolitis in young infants: a multicenter randomized controlled trial (TRAMONTANE study)
Authors: Christophe Milési, Sandrine Essouri, Robin Pouyau, Jean-Michel Liet, Mickael Afanetti, Aurélie Portefaix, Julien Baleine, Sabine Durand, Clémentine Combes, Aymeric Douillard, Gilles Cambonie
Journal: Intensive Care Medicine (2017)
Reply
Authors: P J Hainsworth, T W J Lennard
Journal: Gut (1994)

Imaging of the common bile duct EDITOR,-The finding by Hainsworth et al, that the combination of clinical history, liver function tests, and ultrasonography generated a negative predictive value of 91% in the age range 21-88 (unit A) (Gut 1994; 35: 991-5), implies that, in subgroups such as the elderly, characterised by a high degree of prior probability of cholelithiasis,l and, hence, choledocholithiasis,2 the negative predictive value of these diagnostic criteria might well be lower, because the negative predictive power is inversely correlated with the prevalence of the condition under diagnostic considera- tion.3 4 With increasing age, therefore, there should be greater justification for routine imaging of the common bile duct either by ERCP or by cystic duct cholangiography, in prospective candidates for laparoscopic cholecystectomy.
Identification of tumor biomarkers for sunitinib in advanced renal cell carcinoma (RCC).
Authors: Hongyue Dai, Mayer N. Fishman, Keith A. Ching, James Andrew Williams, Jamie K. Teer, Patricia A. English, Yonghong Zhang, Brion W. Murray, Naveen Kumar, Shane Huntsman, Anders E. Berglund, William S. Dalton, Ewa Matczak, Jean-Francois Martini
Journal: Journal of Clinical Oncology (2015)

470 Background: Sunitinib is a standard of care for advanced RCC. Despite efforts to identify predictive molecular markers for patient selection, none are available, likely due to multiple resistance mechanisms. Using the Total Cancer Care (TCC) database, which integrates patient clinical, molecular, and biospecimen data, we devised a tumor genomics and transcriptomics experiment to identify differences between RCC patients who derive prolonged clinical benefit from sunitinib versus those who are resistant. Methods: A discovery set of 34 RCC patients treated with sunitinib at the approved regimen were identified in the TCC database (n=16 treated for ≤6 months, having primarily discontinued for reasons other than tolerability; n=18 treated for ≥18 months). Tumor samples were analyzed by whole exome sequencing (WES) and by parallel 400-gene expression profiling. Following gene mutation identification and supervised gene expression analysis, molecular differences between the two groups were identified and tested for potential association with treatment duration. Results: Of the 34 cases identified, 24 remained for analysis following sample QC failure and clinical review (n=10 and 14 treated for ≤6 and ≥18 months, respectively). Gene expression analysis revealed a 37-gene signature associated with treatment duration: MAPK8 (JNK1) was a leading candidate biomarker (Pearson correlation with log [treatment duration]=–0.70; p=0.06 after Bonferroni multiplicity correction). Pathway-based WES analyses identified 25 potential variants of interest, none remaining statistically significant after correction. However, following genome-wide analysis, a single variant in an intronic region of ING3 was statistically associated with treatment duration (p=0.02). Conclusions: Activation of the PI3K/AKT pathway was a marker of resistance to sunitinib. In contrast, activation of the angiogenic, NOTCH, or JAK-STAT pathways was, to some degree, associated with sensitivity to therapy. However, neither VHL alteration nor lack of expression, nor alteration in chromatin-rearrangement genes, was associated with sunitinib treatment duration. These findings require further validation in a larger and independent cohort.
Transposable Element-Mediated Balancing Selection at <i>Hsp90</i> Underlies Embryo Developmental Variation
Authors: Bing Chen, Bo Zhang, Lingling Xu, Qing Li, Feng Jiang, Pengcheng Yang, Yanan Xu, Le Kang
Journal: Molecular Biology and Evolution (2017)

Understanding the roles of transposable elements (TEs) in the evolution of genome and adaptation is a long-sought goal. Here, we present a new model of TE co-option, in which a TE is harnessed by an essential gene and confers local adaptation through heterozygote advantage. We characterized a human Alu-like TE family, the Lm1 elements, in the genome of the migratory locust Locusta migratoria that harbors 0.7 million copies of the elements. Scanning Lm1 insertions in the natural locust populations revealed the widespread high polymorphism of Lm1. An Lm1 was recruited into the coding region of Heat-shock protein 90 (Hsp90), an important molecular chaperone for diverse signal transduction and developmental pathways. Only heterozygotes of the allele are present in natural populations. Allele frequency increases with decreased latitudes in east coastal China, even increasing up to 76% in southern populations. Regions flanking the Lm1 insertion display clear signatures of a selective sweep linked to Lm1. The Lm1-mediated Hsp90 mutation is consequential for the embryonic development of locust. Heterozygous embryos develop faster than the wild type, particularly when cued by long-day parental photoperiod. The heterozygotes also present a reduced within-population variation in embryonic development, i.e., high developmental synchrony of embryos. The naturally occurring Hsp90 mutation could facilitate multivoltinism and developmental synchronization of the locust in southern tropical region. These results revealed a genetic mechanism behind microevolutionary changes in which balancing selection may have acted to maintain the heterozygote advantage through TE co-option in essential genes.
Brain Emboli After Left Ventricular Endocardial Ablation
Authors: Isaac R. Whitman, Rachel A. Gladstone, Nitish Badhwar, Henry H. Hsia, Byron K. Lee, S. Andrew Josephson, Karl M. Meisel, William P. Dillon, Christopher P. Hess, Edward P. Gerstenfeld, Gregory M. Marcus
Journal: Circulation (2017)

Catheter ablation for ventricular tachycardia and premature ventricular complexes (PVCs) is common. Catheter ablation of atrial fibrillation is associated with a risk of cerebral emboli attributed to cardioversions and numerous ablation lesions in the low-flow left atrium, but cerebral embolic risk in ventricular ablation has not been evaluated.We enrolled 18 consecutive patients meeting study criteria scheduled for ventricular tachycardia or PVC ablation over a 9-month period. Patients undergoing left ventricular (LV) ablation were compared with a control group of those undergoing right ventricular ablation only. Patients were excluded if they had implantable cardioverter defibrillators or permanent pacemakers. Radiofrequency energy was used for ablation in all cases and heparin was administered with goal-activated clotting times of 300 to 400 seconds for all LV procedures. Pre- and postprocedural brain MRI was performed on each patient within a week of the ablation procedure. Embolic infarcts were defined as new foci of reduced diffusion and high signal intensity on fluid-attenuated inversion recovery brain MRI within a vascular distribution.The mean age was 58 years, half of the patients were men, half had a history of hypertension, and the majority had no known vascular disease or heart failure. LV ablation was performed in 12 patients (ventricular tachycardia, n=2; PVC, n=10) and right ventricular ablation was performed exclusively in 6 patients (ventricular tachycardia, n=1; PVC, n=5). Seven patients (58%) undergoing LV ablation experienced a total of 16 cerebral emboli, in comparison with zero patients undergoing right ventricular ablation (P=0.04). Seven of 11 patients (63%) undergoing a retrograde approach to the LV developed at least 1 new brain lesion.More than half of patients undergoing routine LV ablation procedures (predominately PVC ablations) experienced new brain emboli after the procedure. Future research is critical to understanding the long-term consequences of these lesions and to determining optimal strategies to avoid them.
Comparison of Novel Markers in Prediction of Coronary Heart Disease Risk: the Rotterdam Study
Authors: Maryam Kavousi, Suzette Elias-Smale, Joost H. Rutten, Rozemarijn Vliegenthart Proenca, Matthijs Oudkerk, Moniek P. de Maat, Albert Hofman, Ewout Steyerberg, Anton H. van den Meiracker, Jacqueline C. Witteman
Journal: Circulation (2010)
Outcome of Therapy-Related Acute Promyelocytic Leukemia (t-APL) with or without Arsenic Trioxide (ATO) as a Component of Frontline Therapy.
Authors: Farshid Dayyani, Hagop M. Kantarjian, Susan O'Brien, Sherry Pierce, Stefan Faderl, Guillermo Garcia-Manero, Jorge Cortes-Franco, Farhad Ravandi
Journal: Blood (2009)
Minimizing Therapy for Patients with Acute Promyelocytic Leukemia: Efficacy of Single Cycle of Arsenic-Based Consolidation Therapy.
Authors: Steven D. Gore, Lawrence Morris, Ivana Gojo, Marcel P. Devetten, Katarzyna Jamieson, Mikkael A. Sekeres, Robert J. Arceci, Robert L. Redner, Tianna Dauses, Esther L Schachter-Tokarz, Ibitayo Owoeye, Robert E. Gallagher
Journal: Blood (2008)
Influence of risk factors for renal cell carcinoma (RCC) on outcome of patients (pts) with metastatic disease treated with sunitinib.
Authors: Daniel Keizman, Maya Ish-Shalom, Jason David Taksey, Roberto Pili, Hans J. Hammers, Mario A. Eisenberger, Ben Boursi, Raanan Berger, Natalie Maimon, Maya Gottfried, Henry Hayat, Avivit Peer, Svetlana Kovel, Avishay Sella, Michael Anthony Carducci
Journal: Journal of Clinical Oncology (2012)

437 Background: Obesity, smoking, hypertension (HTN) and diabetes (DM) are risk factors for RCC development. Their presence has been associated with a worse outcome of therapy (tx) in various metastatic cancers. We sought to determine their influence on the progression free survival (PFS) and overall survival (OS) of Su tx in mRCC. Methods: We performed a multicentre retrospective study of pts with mRCC, who were treated with Su. We analyzed the pre-tx status of smoking (active vs past vs never), BMI (obese=BMI≥30 vs overweight=BMI 25-29.9 vs normal weight=BMI &lt;25), HTN, DM, and known prognostic factors including past nephrectomy, clear cell/non clear cell histology, time from initial diagnosis to Su tx, &gt; 2 metastasis (mets) sites, lung/liver/bone mets, ECOG performance status, anemia, calcium level &gt; 10 mg/dL, elevated alkaline phosphatase (AP), platelets count, pre-tx neutrophil to lymphocyte ratio (NLR) &gt;3, Su induced HTN, use of angiotensin system inhibitors (ASIs), past cytokines/targeted tx, and mean Su dose/cycle. PFS and OS were determined by the Kaplan-Meier method. Multivariate analyses using Cox Regression model were performed to determine their independent effect. Results: Between 2004-2011, 209 pts with mRCC were treated with Su. 40 pts were active smoker, 51 obese, 55 diabetic, and 122 had pre-tx HTN. In the entire pt cohort, median PFS was 8 months (mos) and OS 15 mos. Factors associated with PFS were active smoking (HR 2.5, p= 0.005, median PFS 4 vs 10 mos in past smokers vs 10 mos in never smokers), non clear cell histology (HR 1.8, p=0.023), pre-tx NLR &gt;3 (HR 0.2, p&lt;0.0001) and the use of ASIs (HR 1.66, p=0.028). Factors associated with OS were were active smoking (HR 2.1, p= 0.03, median OS 8.5 vs 18 mos in past smokers vs 18 mos in never smokers), AP (HR 1.76, p=0.049), pre-tx NLR &gt;3 (HR 0.294, p&lt;0.0001), and liver mets (HR 0.553, p=0.04). BMI, DM, and pre-tx HTN were not associated with PFS or OS. Conclusions: Active smoking may decrease the PFS and OS of pts with mRCC that are treated with Su. BMI, DM, and pre-tx HTN were not found to be associated with outcome. These results should be investigated prospectively, and if validated applied in clinical practice and clinical trials.
Registry-Based Prospective, Active Surveillance of Medical-Device Safety
Authors: Frederic S. Resnic, Arjun Majithia, Danica Marinac-Dabic, Susan Robbins, Henry Ssemaganda, Kathleen Hewitt, Angelo Ponirakis, Nilsa Loyo-Berrios, Issam Moussa, Joseph Drozda, Sharon-Lise Normand, Michael E. Matheny
Journal: New England Journal of Medicine (2017)

The process of assuring the safety of medical devices is constrained by reliance on voluntary reporting of adverse events. We evaluated a strategy of prospective, active surveillance of a national clinical registry to monitor the safety of an implantable vascular-closure device that had a suspected association with increased adverse events after percutaneous coronary intervention (PCI).We used an integrated clinical-data surveillance system to conduct a prospective, propensity-matched analysis of the safety of the Mynx vascular-closure device, as compared with alternative approved vascular-closure devices, with data from the CathPCI Registry of the National Cardiovascular Data Registry. The primary outcome was any vascular complication, which was a composite of access-site bleeding, access-site hematoma, retroperitoneal bleeding, or any vascular complication requiring intervention. Secondary safety end points were access-site bleeding requiring treatment and postprocedural blood transfusion.We analyzed data from 73,124 patients who had received Mynx devices after PCI procedures with femoral access from January 1, 2011, to September 30, 2013. The Mynx device was associated with a significantly greater risk of any vascular complication than were alternative vascular-closure devices (absolute risk, 1.2% vs. 0.8%; relative risk, 1.59; 95% confidence interval [CI], 1.42 to 1.78; P<0.001); there was also a significantly greater risk of access-site bleeding (absolute risk, 0.4% vs. 0.3%; relative risk, 1.34; 95% CI, 1.10 to 1.62; P=0.001) and transfusion (absolute risk, 1.8% vs. 1.5%; relative risk, 1.23; 95% CI, 1.13 to 1.34; P<0.001). The initial alerts occurred within the first 12 months of monitoring. Relative risks were greater in three prespecified high-risk subgroups: patients with diabetes, those 70 years of age or older, and women. All safety alerts were confirmed in an independent sample of 48,992 patients from April 1, 2014, to September 30, 2015.A strategy of prospective, active surveillance of a clinical registry rapidly identified potential safety signals among recipients of an implantable vascular-closure device, with initial alerts occurring within the first 12 months of monitoring. (Funded by the Food and Drug Administration and others.).
Role of NOD1 in Heart Failure Progression via Regulation of Ca 2+ Handling
Authors: Almudena Val-Blasco, María Jose G.M. Piedras, Gema Ruiz-Hurtado, Natalia Suarez, Patricia Prieto, Silvia Gonzalez-Ramos, Nieves Gómez-Hurtado, Carmen Delgado, Laetitia Pereira, Gemma Benito, Carlos Zaragoza, Nieves Domenech, María Generosa Crespo-Leiro, Daniel Vasquez-Echeverri, Gabriel Nuñez, Eduardo Lopez-Collazo, Lisardo Boscá, María Fernández-Velasco
Journal: Journal of the American College of Cardiology (2017)
Angiogenesis Assays for the Evaluation of Angiogenic Properties of Orthopaedic Biomaterials – A General Review
Authors: Wai Ching Liu, Shihui Chen, Lizhen Zheng, Ling Qin
Journal: Advanced Healthcare Materials (2017)

Vascularization is an essential process in bone formation, remodeling and regeneration during both bone development and fracture repair. Vascularization remains a big challenge directly leading to the final success of newly regenerated bone. In this review, the advantages and disadvantages of different angiogenesis assays and bone defect models are described in details for investigating revascularization of materials of interest. Unlike conventional angiogenesis study with growth factors or pharmaceutical molecules performed in two‐dimension, special considerations are taken into account whether these assays can be translated for testing three‐dimensional implantable devices. Over the years, accurate and quantifiable in vitro, ex vivo and in vivo assays have been extensively demonstrated to be useful in examining how new blood vessels grow. These methods can contribute to the fundamental understanding of angiogenic properties of the materials, but a bone defect model is still pivotal in order to understand the cascade actions of angiogenesis along with bone formation. Finally, angiogenesis and osteogenesis are both complex processes interacting with each other, the choice of which assay to be performed should adequately address the clinical relevance and reflect the sequence of responses of revascularization of the test materials.
Postmortem Genetic Testing for Sudden Unexpected Death
Authors: Steven J. Schrodi
Journal: JAMA (2017)

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Abstract P222: Significant Inverse Association of Blood Levels of Marine Omega-3 Fatty Acids with Coronary Artery Calcification in Men in Japan
Authors: Akira Sekikawa, Marnie Bertolet, Abhishek Vishnu, Vasudha Ahuja, Rhobert W Evans, Lewis H Kuller, Akira Fujiyoshi, Takashi Hisamatsu, Takashi Kadowaki, Aya Kadota, Sayaka Kadowaki, Hisatomi Arima, Katsuyuki Miura, Hirotsugu Ueshima
Journal: Circulation (2016)

Background: Coronary artery calcification (CAC) is an established biomarker of coronary atherosclerosis and predicts future cardiovascular (CV) events. Basic science shows that marine omega-3 fatty acids (OM3) have anti-atherogenic properties yet previous studies in Western countries reported that dietary intake of OM3 had no significant association with CAC. Dietary intake of OM3 in Japan is &gt;10x higher than in the US. We hypothesize that blood levels of OM3 in Japanese have a significant inverse association with CAC. Methods: A population-based sample of 982 men in Kusatsu, Shiga, Japan without CV disease was examined for blood levels of OM3, CV risk factors, and CAC. CAC was assessed by electron-beam tomography and quantified using the Agatston method. OM3 was measured by gas-liquid chromatography. We analyzed the association of OM3 with CAC scores at 67th and 80th percentiles adjusting for CV risk factors using quantile regression as the distribution of CAC scores is highly skewed. Results: Mean (SD) age of the participants was 58.7 (10.9). Rates (%) of hypertension, diabetes, current smoker were 47.3, 16.3, and 38.4, respectively. Mean (SD) LDL-C and OM3 was 127.8 (33.6) mg/dL and 10.2 (3.2) %, respectively. CAC scores were 0, 2, 19, 83, and 476 at 33th, 50th, 67th, 80th, and 95th percentiles, respectively. Blood levels of OM3 had significant inverse associations with CAC both at 67th and 80th percentiles after adjusting for CV risk factors (Table). Conclusions: This cross sectional study of Japanese whose blood levels of OM3 are 2-fold higher compared to the US shows that OM3 had a significant inverse association with atherosclerosis, suggesting that high blood levels of OM3 may have anti-atherogenic properties.