tbuckley/cabot-search huggingface dataset:
Bidirectional transcription initiation marks accessible chromatin and is not specific to enhancers
Authors: Robert S. Young, Yatendra Kumar, Wendy A. Bickmore, Martin S. Taylor
Journal: Genome biology (2017)

Enhancers are modular regulatory elements that are central to the spatial and temporal regulation of gene expression. Bidirectional transcription initiating at enhancers has been proposed to mark active enhancers and as such has been utilized to experimentally identify active enhancers de novo. Here, we show that bidirectional transcription initiation is a pervasive feature of accessible chromatin, including at enhancers, promoters, and other DNase hypersensitive regions not marked with canonical histone modification profiles. Transcription is less predictive for enhancer activity than epigenetic modifications such as H3K4me1 or the accessibility of DNA when measured both in enhancer assays and at endogenous loci. The stability of enhancer initiated transcripts does not influence measures of enhancer activity and we cannot detect evidence of purifying selection on the resulting enhancer RNAs within the human population. Our results indicate that bidirectional transcription initiation from accessible chromatin is not sufficient for, nor specific to, enhancer activity. Transcription initiating at enhancers may be a frequent by-product of promiscuous RNA polymerase initiation at accessible chromatin and is unlikely to generally play a functional role in enhancer activity.
Recurrently Mutated Genes Differ between Leptomeningeal and Solid Lung Cancer Brain Metastases
Authors: Yingmei Li, Boxiang Liu, Ian David Connolly, Bina Wasunga Kakusa, Wenying Pan, Seema Nagpal, Stephen B. Montgomery, Melanie Hayden Gephart
Journal: Journal of Thoracic Oncology (2018)
Generalizable representations of pain, cognitive control, and negative emotion in medial frontal cortex
Authors: Philip A. Kragel, Michiko Kano, Lukas Van Oudenhove, Huynh Giao Ly, Patrick Dupont, Amandine Rubio, Chantal Delon-Martin, Bruno L. Bonaz, Stephen B. Manuck, Peter J. Gianaros, Marta Ceko, Elizabeth A. Reynolds Losin, Choong-Wan Woo, Thomas E. Nichols, Tor D. Wager
Journal: Nature Neuroscience (2017)
Nerve Regeneration: Human Periodontal Ligament‐ and Gingiva‐derived Mesenchymal Stem Cells Promote Nerve Regeneration When Encapsulated in Alginate/Hyaluronic Acid 3D Scaffold (Adv. Healthcare Mater. 24/2017)
Authors: Sahar Ansari, Ivana M. Diniz, Chider Chen, Patricia Sarrion, Ali Tamayol, Benjamin M. Wu, Alireza Moshaverinia
Journal: Advanced Healthcare Materials (2017)

Sahar Ansari and co-workers fabricate a 3D delivery system based on alginate/hyaluronic hydrogel in article number 1700670. The Encapsulated Periodontal Ligament Stem Cells and Gingival Mesenchymal Stem Cells demonstrate positive β-tubulin III staining after four weeks of in vitro differentiation in the presence of recombinant human nerve growth factor (β-NGF) and high levels of gene expression related to neurogenic differentiation. This system has the potential to be used for cell therapy in the repair or regeneration of damaged nerves.
Purse-string transoral outlet reduction (TORe) is effective at inducing weight loss and improvement in metabolic comorbidities after Roux-en-Y gastric bypass
Authors: Pichamol Jirapinyo, Paul Kröner, Christopher Thompson
Journal: Endoscopy (2017)

Abstract Background and study aims Transoral outlet reduction (TORe), performed using a traditional interrupted or a recently described purse-string suture pattern, is effective at inducing short- and mid-term weight loss in patients with weight regain after Roux-en-Y gastric bypass (RYGB). We aimed to determine the technical feasibility and safety of purse-string TORe and to assess its impact on weight and metabolic profiles. Patients and methods RYGB patients undergoing purse-string TORe were included. The gastrojejunal anastomosis (GJA) was ablated using argon plasma coagulation or dissected using endoscopic submucosal dissection. A suture was used to place stitches around the GJA in a continuous ring fashion. The suture was cinched over a balloon (8 – 12 mm). The primary outcome was technical feasibility. Secondary outcomes were the percentage of total body weight lost (%TWL), adverse events, impact on comorbidities, and predictors of weight loss. Results 252 RYGB patients underwent 260 purse-string TORes. They had regained 52.6 ± 46.4 % of lost weight and weighed 107.6 ± 24.6 kg. The technical success rate was 100 %. At 6 and 12 months, %TWL was 9.6 ± 6.3 and 8.4 ± 8.2. Two serious adverse events (0.8 %) occurred: gastrointestinal bleeding and GJA stenosis. At 12 months, blood pressure, hemoglobin A1c, and ALT had improved. Prior weight regain was associated with %TWL at 12 months (β = 0.07, P = 0.007) after controlling for BMI, pouch size, and number of purse-string rings. Conclusion Purse-string TORe to treat weight regain after RYGB is technically feasible and safe. Additionally, it is associated with improvement in weight and comorbidity profiles up to 12 months post-procedure.
Abstract 14186: Is Mitral Valve Repair Superior to Mitral Valve Replacement in Elderly Patients? Short and Long-term Outcomes From the Past Two Decades
Authors: Miriam Silaschi, Sanjay Chaubey, Mohammad M Uzzamann, Habib Khan, Mrinal Singh, Ranjit Deshpande, Max Baghai, Olaf Wendler
Journal: Circulation (2015)

Background: Due to demographic changes a growing number of elderly patients present with mitral valve (MV) disease. Mitral Valve Repair (MV-repair) is the gold-standard treatment option for patients with MV disease. Nevertheless, in elderly patients there is still controversy if MV-repair improves outcomes of patients compared to mitral valve replacement (MVR). We reviewed results after MV surgery in elderly patients treated at our institution over the past 20 years. Methods: Our in-hospital database was explored for patients who underwent MV surgery between 1994 and 2015. A comparative survival-analysis was performed for MV-repair vs. MVR patients. Cox-regression was applied to adjust for age, valve pathology, ejection fraction (EF) and combined procedures. Results: Of the 1776 patients identified, 356 (20.0%) were aged ≥75 years and received either MV-repair (n=224, 62.9%) or MVR (n=132, 37.1%). Patients with repeat cardiac surgery, endocarditis and concomitant aortic valve replacement were excluded. In 55.8% of MV-repair and 46.2% of MVR procedures were combined (p=0.10). Mean age was 79.3±3.1yrs (MV-repair) vs 78.4±2.9yrs (MVR: p=0.02). Logistic EuroSCORE was 14.8±1.3% (MV-repair) vs. 15.3±16.1% (MVR: p=0.77). Median survival of all patients was 7.4years (95%CI: 6.8-8.1) compared to a survival of 8.5years (95%CI: 8.2-9.4) in the age matched UK population (Ratio 0.87; p=0.01). Thirty-day mortality was 6.3% (MV-repair) vs. 10.6% (MVR, p=0.16). Length of ICU-stay was 1.1±1.6 days vs. 1.0±1.0days (p=0.43). Overall 1-, 2-, 5- and 8-year survival after MV-repair (90.7%, 89.0%, 77.0% and 45.9% vs. 79.5%, 76.5%, 58.9% and 41.4%, p[logrank]=0.02) as well as adjusted survival at 1-, 2-, 5- and 8-years were significantly improved after MV-repair (91.1%, 90.2%, 81.0% and 52.5% vs. 77.7%, 76.1%, 56.2%, 37.0%, p&lt;0.01). After MV-repair, impaired EF was an independent predictor of adverse outcome (p&lt;0.01). Conclusion: Mitral valve surgery is a reliable treatment option with excellent long-term outcomes in elderly patients. Long-term outcomes can be improved in this patient group if mitral valves are repaired.
An Endogenous Vaccine Based on Fluorophores and Multivalent Immunoadjuvants Regulates Tumor Micro-Environment for Synergistic Photothermal and Immunotherapy
Authors: Ling Li, Suleixin Yang, Linjiang Song, Yan Zeng, Tao He, Ning Wang, Chuan Yu, Tao Yin, Li Liu, Xiawei Wei, Qinjie Wu, Yuquan Wei, Li Yang, Changyang Gong
Journal: Theranostics (2017)

Recently, near-infrared (NIR) light-based photothermal therapy (PTT) has been widely applied in cancer treatment. However, in most cases, the tissue penetration depth of NIR light is not sufficient and thus photothermal therapy is unable to completely eradicate deep, seated tumors inevitably leading to recurrence of the tumor. Due to this significant limitation of NIR, improved therapeutic strategies are urgently needed. Methods: We developed an endogenous vaccine based on a novel nanoparticle platform for combinatorial photothermal ablation and immunotherapy. The design was based on fluorophore-loaded liposomes (IR-7-lipo) coated with a multivalent immunoadjuvant (HA-CpG). In vitro PTT potency was assessed in cells by LIVE/DEAD and Annexin V-FITC/PI assays. The effect on bone marrow-derived dendritic cells (BMDC) maturation and antigen presentation was evaluated by flow cytometry (FCM) with specific antibodies. After treatment, the immune cell populations in tumor micro-environment and the cytokines in the serum were detected by FCM and Elisa assay, respectively. Finally, the therapeutic outcome was investigated in an animal model. Results: Upon irradiation with 808 nm laser, IR-7-lipo induced tumor cell necrosis and released tumor-associated antigens, while the multivalent immunoadjuvant improved the expression of co-stimulatory molecules on BMDC and promoted antigen presentation. The combination therapy of PTT and immunotherapy regulated the tumor micro-environment, decreased immunosuppression, and potentiated host antitumor immunity. Most significantly, due to an enhanced antitumor immune response, combined photothermal immunotherapy was effective in eradicating tumors in mice and inhibiting tumor metastasis. Conclusion: This endogenous vaccination strategy based on synergistic photothermal and immunotherapy may provide a potentially effective approach for treatment of cancers, especially those difficult to be surgically removed.
Intraoperative endoscopy prevents technical defect related leaks in laparoscopic Roux-en-Y gastric bypass: A randomized control trial
Authors: Carlos Valenzuela-Salazar, Martin E. Rojano-Rodríguez, Sujey Romero-Loera, Mario E. Trejo-Ávila, Joseph Bañuelos-Mancilla, Roberto Delano-Alonso, Mucio Moreno-Portillo
Journal: International Journal of Surgery (2017)
Re: Richard J. Sylvester, Maurizio A. Brausi, Wim J. Kirkels, et al Long-Term Efficacy Results of EORTC Genito-Urinary Group Randomized Phase 3 Study 30911 Comparing Intravesical Instillations of Epirubicin, Bacillus Calmette-Guerin, and Bacillus Calmette-Guerin plus Isoniazid in Patients with Intermediate- and High-Risk Stage Ta T1 Urothelial Carcinoma of the Bladder. Eur Urol 2010;57:766-73 Reply
Authors: Richard J. Sylvester, Maurizio A. Brausi, Ziya Kirkali, Theo M. de Reijke
Journal: European Urology (2010)
Advances in Magnetic Nanoparticles for Biomedical Applications
Authors: Vanessa Fernandes Cardoso, António Francesko, Clarisse Ribeiro, Manuel Bañobre‐López, Pedro Martins, Senentxu Lanceros‐Mendez
Journal: Advanced Healthcare Materials (2017)

Abstract Magnetic nanoparticles (NPs) are emerging as an important class of biomedical functional nanomaterials in areas such as hyperthermia, drug release, tissue engineering, theranostic, and lab‐on‐a‐chip, due to their exclusive chemical and physical properties. Although some works can be found reviewing the main application of magnetic NPs in the area of biomedical engineering, recent and intense progress on magnetic nanoparticle research, from synthesis to surface functionalization strategies, demands for a work that includes, summarizes, and debates current directions and ongoing advancements in this research field. Thus, the present work addresses the structure, synthesis, properties, and the incorporation of magnetic NPs in nanocomposites, highlighting the most relevant effects of the synthesis on the magnetic and structural properties of the magnetic NPs and how these effects limit their utilization in the biomedical area. Furthermore, this review next focuses on the application of magnetic NPs on the biomedical field. Finally, a discussion of the main challenges and an outlook of the future developments in the use of magnetic NPs for advanced biomedical applications are critically provided.
Development of GPC3-Specific Chimeric Antigen Receptor-Engineered Natural Killer Cells for the Treatment of Hepatocellular Carcinoma
Authors: Min Yu, Hong Luo, Mingliang Fan, Xiuqi Wu, Bizhi Shi, Shengmeng Di, Ying Liu, Zeyan Pan, Hua Jiang, Zonghai Li
Journal: Molecular Therapy (2017)

Chimeric antigen receptor (CAR)-modified natural killer (NK) cells represent a promising immunotherapeutic modality for cancer treatment. However, their potential utilities have not been explored in hepatocellular carcinoma (HCC). Glypian-3 (GPC3) is a rational immunotherapeutic target for HCC. In this study, we developed GPC3-specific NK cells and explored their potential in the treatment of HCC. The NK-92/9.28.z cell line was established by engineering NK-92, a highly cytotoxic NK cell line with second-generation GPC3-specific CAR. Exposure of GPC3+ HCC cells to this engineered cell line resulted in significant in vitro cytotoxicity and cytokine production. In addition, soluble GPC3 and TGF-β did not significantly inhibit the cytotoxicity of NK-92/9.28.z cells in vitro, and no significant difference in anti-tumor activities was observed in hypoxic (1%) conditions. Potent anti-tumor activities of NK-92/9.28.z cells were observed in multiple HCC xenografts with both high and low GPC3 expression, but not in those without GPC3 expression. Obvious infiltration of NK-92/9.28.z cells, decreased tumor proliferation, and increased tumor apoptosis were observed in the GPC3+ HCC xenografts. Similarly, efficient retargeting on primary NK cells was achieved. These results justified clinical translation of this GPC3-specific, NK cell-based therapeutic as a novel treatment option for patients with GPC3+ HCC. Chimeric antigen receptor (CAR)-modified natural killer (NK) cells represent a promising immunotherapeutic modality for cancer treatment. However, their potential utilities have not been explored in hepatocellular carcinoma (HCC). Glypian-3 (GPC3) is a rational immunotherapeutic target for HCC. In this study, we developed GPC3-specific NK cells and explored their potential in the treatment of HCC. The NK-92/9.28.z cell line was established by engineering NK-92, a highly cytotoxic NK cell line with second-generation GPC3-specific CAR. Exposure of GPC3+ HCC cells to this engineered cell line resulted in significant in vitro cytotoxicity and cytokine production. In addition, soluble GPC3 and TGF-β did not significantly inhibit the cytotoxicity of NK-92/9.28.z cells in vitro, and no significant difference in anti-tumor activities was observed in hypoxic (1%) conditions. Potent anti-tumor activities of NK-92/9.28.z cells were observed in multiple HCC xenografts with both high and low GPC3 expression, but not in those without GPC3 expression. Obvious infiltration of NK-92/9.28.z cells, decreased tumor proliferation, and increased tumor apoptosis were observed in the GPC3+ HCC xenografts. Similarly, efficient retargeting on primary NK cells was achieved. These results justified clinical translation of this GPC3-specific, NK cell-based therapeutic as a novel treatment option for patients with GPC3+ HCC.
Abstract 15755: Clinical Trials Associated With Heart Failure Guidelines Are Not Generalizable to Black Populations
Authors: Lonnie T Sullivan, Tiffany Randolph, Chidiebube Egwim, Peter Merrill, Kevin L Thomas
Journal: Circulation (2016)

Introduction: Black individuals have a higher incidence of heart failure (HF) and suffer worse outcomes relative to white individuals. Inclusion of black patients in major randomized clinical trial...
Abstract 14139: New Criteria of Electrocardiographic Diagnosis of Left Ventricular Hypertrophy Were Associated With Cardiovascular Events in Japanese Patients: Japan Morning Surge Home Blood Pressure (J-HOP) Study
Authors: Yusuke Ishiyama, Tomoyuki Kabutoya, Satoshi Hoshide, Kazuomi Kario
Journal: Circulation (2016)

Introduction:  The Cornell product (CP) is an electrocardiographic marker of left ventricular hypertrophy(LVH), but has a high false-negative rate. The relationships between the CP and cardiovascular(CV) event may differ between genders or among ethnicities.   Hypothesis:  We hypothesized that a new modified CP (MCP) would be associated with a poor prognosis in Japanese patients with CV risk factors.   Methods:  Subjects were 3,380 patients enrolled in the Japan Morning Surge Home Blood Pressure Study who had one or more CV risk factors. A CP of ≥2440 mmхms was used to diagnose electrocardiographic LVH (CP-LVH). We also calculated the product of (RaVL+SV3) xQRS (MCP) without adjusting for female gender by adding 8 mm to the sum of (RaVL+SV3). We divided patients into quintiles by the product of MCP, and compared the prognosis of subjects in the highest quintile of MCP (male≥2000 mmхms, female ≥1666 mmхms) with those in the other four quintiles in males and females. The primary endpoints were fatal/nonfatal CV events (myocardial infarction, stroke, hospitalization for heart failure).   Results:  During the mean follow-up period of 48±39 months, there were 139 CV events (88 in males, 51 in females). The CV event incidence was not significantly different between subjects with/without CP-LVH either in males (log rank 1.24, p=0.27) or females (log rank 0.16, p=0.69). In male, subjects in the highest quintile (N=315) were more likely to suffer CV events than those in the other four quintiles of MCP (N=1262; log rank 6.10, p=0.014). A Cox proportional hazards model including age, smoking, drinking, hypertension, dyslipidemia and diabetes revealed that the highest quintile of MCP was an independent predictor of CV events in male (hazard ratio 1.76, 95%CI 1.12-2.75). In female, CV events were similar between the highest quintile (N=361) and the other four quintiles of MCP (N=1442).   Conclusions:  The highest quintile of MCP was associated with CV events in Japanese male patients with CV risk.
Abstract 18374: TCF21 and Aryl-Hydrocarbon Receptor Gene Cooperate to Activate a Pro-Atherosclerotic Gene Expression Program
Authors: Juyong B Kim, Milos Pjanic, Olga Sazanova, Tina Wang, Trieu Nguyen, Clint Miller, Lars Maegdefessel, Ulf Hedin, Thomas Quertermous
Journal: Circulation (2016)

Background:  Recently, the  TCF21  gene was linked to the highly replicated coronary artery disease (CAD) associated polymorphism in the 6q23 locus. We previously reported Aryl Hydrocarbon Receptor ( AHR ) to be a downstream target of TCF21.  AHR  is a ligand-activated transcription factor that mediates the cellular response to environmental contaminants, including dioxin and polycyclic aromatic hydrocarbons (e.g. cigarette), and has recently been associated with CAD in mice and humans. We further characterized the interaction between TCF21 and AHR.   Methods:  The co-regulatory role of TCF21 and AHR on transcription was tested using dual luciferase assay. Luciferase reporter vector containing TCF21 and AHR binding motifs were transfected into HEK293 cells, with or without  TCF21  expressing plasmid. These cells were then treated with 2,3,7,8-Tetrachlorodibenxo- p -dioxin (TCDD) or control. Laser capture microdissection (LCM) was performed on atherosclerotic plaque of  Apoe  (-/-) mouse on high fat diet for 12 weeks. Previously performed ChIP-Seq and ATAC-Seq (Assay for Transposase-Accessible Chromatin using sequencing) data from human coronary artery smooth muscle cells (HCASMC) were analyzed. Position weight matrix for TCF21 and AHR were obtained from the  JASPAR  database.   Results:  We found that  TCF21  over-expression and  AHR  pathway activation additively increased downstream transcription using reporter assay. Furthermore, we found  AHR  level to be higher in plaque in human and mouse atherosclerotic plaques. The TCF21 and AHR binding sites co-localized genome-wide to open chromatin regions of HCASMC, and genes near the overlapped binding sites enriched for pathways relevant to atherosclerosis, including cytokine production, migration and ossification. Using published ChIP-Seq data, we also found that common peaks of AHR-ARNT and TCF21 ChIP-Seq enriched for GWAS SNPs related to coronary artery disease.   Conclusion:  The binding sites of two TFs ,  TCF21  and  AHR , co-localize in HCASMC, and cooperate in transcriptional activation of downstream genes relevant to atherosclerosis. The functional link between TCF21 and AHR provides an opportunity to explore gene by environment interactions in the pathogenesis of CAD.
BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients (vol 17, pg 341, 1997)
Authors: A. Petrij-Bosch, T. Peelen, M. van Vliet, R. van Eijk, R. Olmer, M. Drusedau, F. B. L. Hogervorst, S. Hageman, P. J. W. Arts, M. J. L. Ligtenberg, H. Meijers-Heijboer, J. G. M. Klijn, H. F. A. Vasen, C. J. Cornelisse, L. J. van't Veer, E. Bakker, G. J. van Ommen, P. Devilee
Journal: Nature Genetics (1997)
Abstract 15878: Pulse Pressure and Intraluminal Mean Pressure Regulate Endothelium-Dependent Flow-Mediated Dilation in Cerebral Arteries of Dyslipidemic Mice
Authors: Adeline Raignault, Virginie Bolduc, Frédéric Lesage, Eric Thorin
Journal: Circulation (2014)

Introduction:  In vivo, resting arterial blood pressure in cerebral arteries is pulsatile; however, whether pulse pressure (PP) regulates endothelial shear stress (SS) sensitivity is unknown. The aim of this study was to design a computer-controlled pneumatic system mounted in series with a small vessel pressure myograph generating a PP to test its impact on endothelium-dependent flow-mediated dilatation (FMD) in cerebral arteries from C57Bl/6J (WT) mice and dyslipidemic (LDLR-/-;hApoB+/+, ATX) 3-mo mice.   Methods:  Isolated posterior cerebral arteries (n=10 per group) were pressurized at a mean physiological (60 mm Hg) or high (80 mm Hg) pressure either in static (SP) or PP condition of ±15 mm Hg, at a rate of 550 pulses per minute mimicking resting heart rate in conscious mice. Varying SS (2 to 20 dyn/cm2) was applied to pre-constricted vessels and endothelial sensitivity was assessed by measuring FMD (% of max diameter).   Results:  In arteries isolated from WT mice, FMD was similar in SP and PP conditions for SS up to 15 dyn/cm2. However, starting at 20 dyn/cm2, PP increased FMD (Table). In contrast, at a pressure of 80 mm Hg, FMD (20 dyn/cm2) were reduced, however more in PP than in SP condition. In both SP and PP conditions, cerebral arteries did not dilate (p   Conclusion:  Endothelial SS sensitivity is sensitive to the intraluminal pressure and is regulated by PP, even in the presence of a dysfunctional endothelium.
Tension‐Activated Delivery of Small Molecules and Proteins from Superhydrophobic Composites
Authors: Julia Wang, Yolonda L. Colson, Mark W. Grinstaff
Journal: Advanced Healthcare Materials (2017)

Abstract The fabrication and performance of mechanically responsive multilayer superhydrophobic composites are reported. The application of tensile strain triggers the release of small molecules and proteins from these composites, with different tensile strain magnitudes and coating thickness influencing agent release. These mechanoresponsive composites consist of an absorbent drug core surrounded by an electrosprayed superhydrophobic protective coating that limits drug release in the absence of tensile strain. Coating thickness and applied tensile strain control release of chemotherapeutic cisplatin and enzyme β‐galactosidase, as measured by atomic absorption and UV–vis spectrophotometry, respectively, with preserved in vitro activity. Such mechanically responsive drug delivery devices, when coupled to existing dynamic mechanical forces in the body or integrated with mechanical medical devices, such as stents, will provide local controlled dosing.
Abstract 16279: Measurements of ROS in Subcellular Compartments in Adult Cardiomyocytes in a Model of Heart Failure and Sudden Cardiac Death
Authors: Swati Dey, Deeptankar DeMazumder, Brian O’Rourke
Journal: Circulation (2016)

Intro: Reactive oxygen species (ROS) are central to the pathophysiology of heart failure (HF) and sudden cardiac death (SCD), but the effects of ROS depend on where and how ROS are generated. Inves...