tbuckley/cabot-search huggingface dataset:
Abstract 428: Pharmacologic and Activated Fibroblast-specific Gβγ-GRK2 Inhibition is Protective Following Ischemia Reperfusion Injury
Authors: Joshua G Travers, Fadia A Kamal, Michelle L Nieman, Michelle A Sargent, Jeffery D Molkentin, Burns C Blaxall
Journal: Circulation Research (2016)

Heart failure is a devastating disease characterized by chamber remodeling, interstitial fibrosis and reduced ventricular compliance. Cardiac fibroblasts are responsible for extracellular matrix homeostasis, however upon injury or pathologic stimulation, these cells transform to a myofibroblast phenotype and play a fundamental role in myocardial fibrosis and remodeling. Chronic sympathetic overstimulation induces excess signaling through G protein βγ subunits and ultimately the pathologic activation of G protein-coupled receptor kinase 2 (GRK2). We hypothesized that Gβγ-GRK2 inhibition plays an important role in the cardiac fibroblast to attenuate pathologic myofibroblast activation and cardiac remodeling. To investigate this hypothesis, mice were subjected to ischemia/reperfusion (I/R) injury and treated with the small molecule Gβγ-GRK2 inhibitor gallein. While animals receiving vehicle demonstrated a reduction in overall cardiac function as measured by echocardiography, mice treated with gallein exhibited nearly complete preservation of cardiac function and reduced fibrotic scar formation. We next sought to establish the cell specificity of this compound by treating inducible cardiomyocyte- and activated fibroblast-specific GRK2 knockout mice post-I/R. Although we observed modest restoration in cardiac function in cardiomyocyte-specific GRK2 null mice, treatment of these mice with gallein resulted in further protection against myocardial dysfunction following injury, suggesting a functional role in other cardiac cell types, including fibroblasts. Activated fibroblast-specific GRK2 knockout mice were also subjected to ischemia/reperfusion injury; these animals displayed preserved myocardial function and reduced collagen deposition compared to littermate controls following injury. Furthermore, systemic Gβγ-GRK2 inhibition by gallein did not appear to confer further protection over activated fibroblast-specific GRK2 ablation alone. In summary, these findings suggest a potential therapeutic role for Gβγ-GRK2 inhibition in limiting pathologic myofibroblast activation, interstitial fibrosis and heart failure progression.
Integrative Cistromic and Transcriptomic Analyses Identify CREB Target Genes in Cystic Renal Epithelial Cells
Authors: Zhiheng Liu, Yunjing Liu, Lin Dang, Meijuan Geng, Yongzhan Sun, Yi Lu, Zhongze Fang, Hui Xiong, Yupeng Chen
Journal: Journal of the American Society of Nephrology (2021)

Genome-wide mapping of transcription factor (TF) binding sites is essential to identify a TF's direct target genes in kidney development and diseases. However, due to the cellular complexity of the kidney and limited numbers of a given cell type, it has been challenging to determine the binding sites of a TF in vivo. cAMP response element-binding protein (CREB) is phosphorylated and hyperactive in autosomal dominant polycystic kidney disease (ADPKD). We focus on CREB as an example to profile genomic loci bound by a TF and to identify its target genes using low numbers of specific kidney cells.Cleavage under targets and release using nuclease (CUT&RUN) assays were performed with Dolichos biflorus agglutinin (DBA)-positive tubular epithelial cells from normal and ADPKD mouse kidneys. Pharmacologic inhibition of CREB with 666-15 and genetic inhibition with A-CREB were undertaken using ADPKD mouse models.CUT&RUN to profile genome-wide distribution of phosphorylated CREB (p-CREB) indicated correlation of p-CREB binding with active histone modifications (H3K4me3 and H3K27ac) in cystic epithelial cells. Integrative analysis with CUT&RUN and RNA-sequencing revealed CREB direct targets, including genes involved in ribosome biogenesis and protein synthesis. Pharmacologic and genetic inhibition of CREB suppressed cyst growth in ADPKD mouse models.CREB promotes cystogenesis by activating ribosome biogenesis genes. CUT&RUN, coupled with transcriptomic analysis, enables interrogation of TF binding and identification of direct TF targets from a low number of specific kidney cells.
Human Induced Pluripotent Stem Cell‐Derived Neural Progenitor Cells Produce Distinct Neural 3D In Vitro Models Depending on Alginate/Gellan Gum/Laminin Hydrogel Blend Properties
Authors: Julia Kapr, Laura Petersilie, Thomas Distler, Ines Lauria, Farina Bendt, Clemens M. Sauter, Aldo R. Boccaccini, Christine R. Rose, Ellen Fritsche
Journal: Advanced Healthcare Materials (2021)

Abstract Stable and predictive neural cell culture models are a necessary premise for many research fields. However, conventional 2D models lack 3D cell‐material/‐cell interactions and hence do not reflect the complexity of the in vivo situation properly. Here two alginate/gellan gum/laminin (ALG/GG/LAM) hydrogel blends are presented for the fabrication of human induced pluripotent stem cell (hiPSC)‐based 3D neural models. For hydrogel embedding, hiPSC‐derived neural progenitor cells (hiNPCs) are used either directly or after 3D neural pre‐differentiation. It is shown that stiffness and stress relaxation of the gel blends, as well as the cell differentiation strategy influence 3D model development. The embedded hiNPCs differentiate into neurons and astrocytes within the gel blends and display spontaneous intracellular calcium signals. Two fit‐for‐purpose models valuable for i) applications requiring a high degree of complexity, but less throughput, such as disease modeling and long‐term exposure studies and ii) higher throughput applications, such as acute exposures or substance screenings are proposed. Due to their wide range of applications, adjustability, and printing capabilities, the ALG/GG/LAM based 3D neural models are of great potential for 3D neural modeling in the future.
Linking ecomechanical models and functional traits to understand phenotypic diversity
Authors: Timothy E. Higham, Lara A. Ferry, Lars Schmitz, Duncan J. Irschick, Samuel Starko, Philip S.L. Anderson, Philip J. Bergmann, Heather A. Jamniczky, Leandro R. Monteiro, Dina Navon, Julie Messier, Emily Carrington, Stacy C. Farina, Kara L. Feilich, L. Patricia Hernandez, Michele A. Johnson, Sandy M. Kawano, Chris J. Law, Sarah J. Longo, Christopher H. Martin, Patrick T. Martone, Alejandro Rico-Guevara, Sharlene E. Santana, Karl J. Niklas
Journal: Trends in Ecology & Evolution (2021)

Physical principles and laws determine the set of possible organismal phenotypes. Constraints arising from development, the environment, and evolutionary history then yield workable, integrated phenotypes. We propose a theoretical and practical framework that considers the role of changing environments. This 'ecomechanical approach' integrates functional organismal traits with the ecological variables. This approach informs our ability to predict species shifts in survival and distribution and provides critical insights into phenotypic diversity. We outline how to use the ecomechanical paradigm using drag-induced bending in trees as an example. Our approach can be incorporated into existing research and help build interdisciplinary bridges. Finally, we identify key factors needed for mass data collection, analysis, and the dissemination of models relevant to this framework.
Long-term safety and efficacy of emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV-1 pre-exposure prophylaxis: week 96 results from a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Onyema Ogbuagu, Peter J Ruane, Daniel Podzamczer, Laura C Salazar, Keith Henry, David M Asmuth, David Wohl, Richard Gilson, Yongwu Shao, Ramin Ebrahimi, Stephanie Cox, Alexander Kintu, Christoph Carter, Moupali Das, Jared M Baeten, Diana M Brainard, Gary Whitlock, Jason M Brunetta, Gitte Kronborg, Christoph D Spinner, Andrea Antinori, Vanessa Apea, David Asmuth, Ann Avery, Paul Benson, Colm Bergin, Mezgebe Berhe, Indira Brar, Cynthia Brinson, Jason Brunetta, Jeffrey Burack, Thomas Campbell, Michelle Cespedes, Amanda Clarke, Megan Coleman, Josep Coll, Manuel Crespo Casal, Catherine Creticos, Gordon Crofoot, Frederick Cruickshank, Eric Cua, Eric Daar, Joseph de Wet, Edwin DeJesus, Jorge Del Romero Guerrero, William Dinges, Susanne Doblecki-Lewis, Taylor Donovan, Olamide Dosekun, Jason Flamm, Joel Gallant, Jan Gerstoft, Richard Gilson, Jay Gladstein, Robert Grant, Robert Grossberg, Bernhard Haas, Jason Halperin, W. David Hardy, Charles Hare, Shawn Hassler, Richard Hengel, William Henry, Theo Hodge, Sybil Hosek, Christopher Hurt, Michelle Iandiorio, Heiko Jessen, Stephen Kegg, Gabriele Knecht, Gitte Kronborg, Ivanka Krznaric, Anthony LaMarca, Carsten Schade Larsen, Olav Ditlevsen Larsen, Adriano Lazzarin, Clifford Leen, Christopher Lucasti, Patrick Mallon, Sharon Mannheimer, Martin Markowitz, Claudia Martorell, Kenneth Mayer, Anthony Mills, Jean-Michel Molina, Sheldon Morris, Karam Mounzer, Nneka Nwokolo, Onyema Ogbuagu, Olayemi Osiyemi, Andrew Petroll, Patrick Philibert, John Phoenix, Gilles Pialoux, Daniel Podzamczer, Frank Post, Maria Prins, Moti Ramgopal, Bruce Rashbaum, Iain Reeves, Gary Richmond, Armin Rieger, Peter Ruane, Laura Salazar, Anthony Scarsella, Gabriel Schembri, Mia Scott, Peter Shalit, Gary Sinclair, Magdalena Sobieszczyk, Christoph Spinner, Jeffrey Stephens, Jason Szabo, Stephen Taylor, Melanie Thompson, Cecile Tremblay, Benoit Trottier, Gene Voskuhl, Barbara Wade, David Wohl, Kimberly Workowski, Sigal Yawetz, Benjamin Young
Journal: The Lancet HIV (2021)
Use of Preventive Aspirin Among Older US Adults With and Without Diabetes
Authors: Elizabeth Y. Liu, Mohammed E. Al-Sofiani, Hsin-Chieh Yeh, Justin B. Echouffo-Tcheugui, Joshua J. Joseph, Rita R. Kalyani
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The net benefit of aspirin for prevention of cardiovascular disease (CVD), particularly primary prevention, remains debated in people with and without diabetes. Recent studies suggest that the benefits of preventive aspirin may be outweighed by the potential for harm in older adults; therefore, it is important to monitor current aspirin use in order to minimize risk for future harm in the oldest segment of the population. <h3>Objective</h3> To determine the prevalence of preventive aspirin use in older US adults with and without diabetes for both primary and secondary prevention by age, sex, and CVD risk category. <h3>Design, Setting, and Participants</h3> This cross-sectional analysis used nationally representative data from the National Health and Nutrition Examination Survey from 2011 to 2018. A total of 7103 individuals 60 years or older with and without diabetes completed a questionnaire on preventive aspirin use. Statistical analyses were performed from July 1, 2019, to April 1, 2021. <h3>Main Outcomes and Measures</h3> Preventive aspirin use was defined as participants' self-reported use of low-dose aspirin therapy based on their physician's advice or their own decision. <h3>Results</h3> A total of 7103 individuals (mean [SD] age, 69.6 [0.1] years; 45.2% men; 75.8% White participants) were evaluated. Overall, 61.7% of older US adults with diabetes vs 42.2% without diabetes used aspirin. Among people with diabetes, in multivariable logistic models adjusting for race, sex, education, CVD risk category, and body mass index, the likelihood of aspirin use in older vs younger age categories (reference: 60-69 years) did not differ. Among people without diabetes, aspirin use was significantly greater in older age categories vs the reference (model 3, 70-79 years, odds ratio [OR], 1.50; 95% CI, 1.23-1.83; model 3, ≥80 years, OR, 1.59; 95% CI, 1.24-2.04). An estimated 9.9 million US adults 70 years or older with or without diabetes reported taking aspirin for primary prevention. The likelihood of aspirin use for primary prevention in those at high vs low risk for CVD did not differ among older adults with diabetes (model 3, OR, 1.69; 95% CI, 0.65-4.39) but was significantly higher in those without diabetes (model 3, OR, 2.46; 95% CI, 1.63-3.71). Women vs men with diabetes were less likely to be using aspirin for primary prevention (model 3, OR, 0.63; 95% CI, 0.48-0.83). <h3>Conclusions and Relevance</h3> This cross-sectional study found that preventive aspirin use was higher among older adults with diabetes than in those without diabetes. Results suggest that 9.9 million older US adults who previously took aspirin for primary prevention would not be recommended for its continued use, particularly among those with diabetes.
Inkjet Printed Textile Force Sensitive Resistors for Wearable and Healthcare Devices
Authors: Beomjun Ju, Inhwan Kim, Braden M. Li, Caitlin G. Knowles, Amanda Mills, Landon Grace, Jesse S. Jur
Journal: Advanced Healthcare Materials (2021)

Pressure sensors for wearable healthcare devices, particularly force sensitive resistors (FSRs) are widely used to monitor physiological signals and human motions. However, current FSRs are not suitable for integration into wearable platforms. This work presents a novel technique for developing textile FSRs (TFSRs) using a combination of inkjet printing of metal-organic decomposition silver inks and heat pressing for facile integration into textiles. The insulating void by a thermoplastic polyurethane (TPU) membrane between the top and bottom textile electrodes creates an architectured piezoresistive structure. The structure functions as a simple logic switch where under a threshold pressure the electrodes make contact to create conductive paths (on-state) and without pressure return to the prior insulated condition (off-state). The TFSR can be controlled by arranging the number of layers and hole diameters of the TPU spacer to specify a wide range of activation pressures from 4.9 kPa to 7.1 MPa. For a use-case scenario in wearable healthcare technologies, the TFSR connected with a readout circuit and a mobile app shows highly stable signal acquisition from finger movement. According to the on/off state of the TFSR with LED bulbs by different weights, it can be utilized as a textile switch showing tactile feedback.
Identification of Relapse Risk Using a Multiparameter Flow Cytometry-Based Detection of Minimal Residual Disease in Adult Patients with Acute Myeloid Leukemia at ELN Intermediate-Risk
Authors: Marco Chiarini, Viviana Giustini, Francesco Buccisano, Erika Borlenghi, Mirko Farina, Chiara Cattaneo, Diego Bertoli, Federico Serana, Alessandro Montanelli, Luisa Imberti, Aldo M. Roccaro, Maria Ilaria Del Principe, Luca Maurillo, Adriano Venditti, Giuseppe Rossi
Journal: Blood (2017)
Abstract #2984: Benzyl isothiocyanate induces heat shock protein 70 expression and inhibits NF-\#954;B activation in human pancreatic cancer cells
Authors: Sanjay Batra, Ravi Sahu, Sanjay Srivastava
Journal: Cancer Research (2009)

We have previously demonstrated that benzyl isothiocyanate (BITC) significantly reduces the survival of human pancreatic cancer cells by inducing cell cycle arrest and apoptosis without having any effect on normal pancreatic cells. In the present study, we found that BITC treatment for 24h caused significant decrease in the transcriptional activity of NF-\#954;B/p65 in Capan-2 human pancreatic cancer cells. Further, BITC treatment also decreased the phosphorylation of NF-\#954;B/p65 at Ser 536 as well as its DNA binding activity in the nuclear fraction of the cells. Current studies also reveal that treatment of Capan-2 cells with BITC significantly induced heat shock protein (Hsp70) expression. Heat shock proteins (Hsp\#8217;s) have been shown to be regulated by variety of stresses including chemical, UV radiation, ischemia, and free radicals. Our results nonetheless indicate the generation of ROS by BITC treatment. The kinetics of Hsp70 induction by BITC treatment correlated with the decreased nuclear translocation of NF-\#954;B/p65. For example, induction in Hsp70 expression appears to be associated with decreased nuclear translocation of NF-\#954;B/p65, 8h after BITC treatment. Co-immunoprecipitation studies revealed about 4 fold increased association of NF-\#954;B/p65 with Hsp70 in Capan-2 cells treated with 10 µM BITC for 24h. In addition, BITC treatment also caused concentration and time dependent decrease in histone deacetylase 3 (HDAC3) expression in Capan-2 cells. HDACs are known to play role in the regulation of NF-\#954;B/p65. Decrease in HDAC3 expression and increase in Hsp70 expression by BITC may be attributed to the inactivation of NF-\#954;B thus implicating multi-level regulation of NF-\#954;B in Capan-2 cells. Further studies on silencing of Hsp70 expression using SiRNA are in progress to delineate the molecular mechanisms of BITC [Supported in part by RO1 grant CA106953 (to S.K.S.) awarded by National Cancer Institute].  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2984.
心筋梗塞後のn-3多価不飽和脂肪酸とビタミンEの食事補給:GISSI-Prevenzione試験の結果
Authors: Marchioli R, Valagussa F, Franzosi M G, Geraci E, Mininni N, Nicolosi G L, Santini M, Tavazzi L, Vecchio C
Journal: The Lancet (1999)
Anti-NKG2C/IL-15/anti-CD33 killer engager directs primary and iPSC-derived NKG2C+ NK cells to target myeloid leukemia
Authors: Emily Chiu, Martin Felices, Frank Cichocki, Zachary Davis, Hongbo Wang, Katie Tuninga, Daniel A. Vallera, Tom Lee, Ryan Bjordahl, Karl Johan Malmberg, Bahram Valamehr, Jeffrey S. Miller
Journal: Molecular Therapy (2021)

Natural killer (NK) cells mediate the cytolysis of transformed cells and are currently used as an adoptive cellular therapy to treat cancer. Infection with human cytomegalovirus has been shown to expand a subset of "adaptive" NK cells expressing the activation receptor NKG2C that have preferred functional attributes distinct from conventional NK cells. Because NKG2C delivers a strong activating signal to NK cells, we hypothesized that NKG2C could specifically trigger NK-cell-mediated antitumor responses. To elicit a tumor-directed response from NKG2C+ NK cells, we created an anti-NKG2C/IL-15/anti-CD33 killer engager called NKG2C-KE that directs NKG2C+ cells to target CD33+ cells and tumor-associated antigen expressed by acute myelogenous leukemia cells. The NKG2C-KE induced specific degranulation, interferon-γ production, and proliferation of NKG2C-expressing NK cells from patients who reactivated cytomegalovirus after allogeneic transplantation. The NKG2C-KE was also tested in a more homogeneous system using induced pluripotent stem cell (iPSC)-derived NK (iNK) cells that have been engineered to express NKG2C at high levels. The NKG2C-KE triggered iNK-cell-mediated cytotoxicity against CD33+ cells and primary AML blasts. The NKG2C-KE-specific interaction with adaptive NK and NKG2C+ iNK cells represents a new immunotherapeutic paradigm that uniquely engages highly active NK cells to induce cytotoxicity against AML through redirected targeting.
Governance aspects of large-scale implementation of automated surveillance of healthcare-associated infections
Authors: Stephanie M. van Rooden, Olov Aspevall, Elena Carrara, Sophie Gubbels, Anders Johansson, Jean-Christophe Lucet, Siddharth Mookerjee, Zaira R. Palacios-Baena, Elisabeth Presterl, Evelina Tacconelli, Mohamed Abbas, Michael Behnke, Petra Gastmeier, Maaike S.M. van Mourik
Journal: Clinical Microbiology and Infection (2021)

Surveillance of healthcare-associated infections (HAI) is increasingly automated by applying algorithms to routine-care data stored in electronic health records. Hitherto, initiatives have mainly been confined to single healthcare facilities and research settings, leading to heterogeneity in design. The PRAISE network - Providing a Roadmap for Automated Infection Surveillance in Europe - designed a roadmap to provide guidance on how to move automated surveillance (AS) from the research setting to large-scale implementation. Supplementary to this roadmap, we here discuss the governance aspects of automated HAI surveillance within networks, aiming to support both the coordinating centres and participating healthcare facilities as they set up governance structures and to enhance involvement of legal specialists.This article is based on PRAISE network discussions during two workshops. A taskforce was installed that further elaborated governance aspects for AS networks by reviewing documents and websites, consulting experts and organizing teleconferences. Finally, the article has been reviewed by an independent panel of international experts.Strict governance is indispensable in surveillance networks, especially when manual decisions are replaced by algorithms and electronically stored routine-care data are reused for the purpose of surveillance. For endorsement of AS networks, governance aspects specifically related to AS networks need to be addressed. Key considerations include enabling participation and inclusion, trust in the collection, use and quality of data (including data protection), accountability and transparency.This article on governance aspects can be used by coordinating centres and healthcare facilities participating in an AS network as a starting point to set up governance structures. Involvement of main stakeholders and legal specialists early in the development of an AS network is important for endorsement, inclusivity and compliance with the laws and regulations that apply.
Immune checkpoint inhibitor treatment and atherosclerotic cardiovascular disease: an emerging clinical problem
Authors: Kikkie Poels, Suzanne I.M. Neppelenbroek, Marie José Kersten, M. Louisa Antoni, Esther Lutgens, Tom T.P. Seijkens
Journal: Journal for ImmunoTherapy of Cancer (2021)

Antibody-mediated blockade of co-inhibitory molecules such as cytotoxic T lymphocyte-associated protein 4, PD1 and PDL1 elicits potent antitumor responses and improves the prognosis of many patients with cancer. As these immune checkpoint inhibitors (ICIs) are increasingly prescribed to a diverse patient population, a broad range of adverse effects is emerging. Atherosclerosis, a lipid-driven chronic inflammatory disease of the large arteries, may be aggravated by ICI treatment. In this review, we discuss recent clinical studies that analyze the correlation between ICI use and atherosclerotic cardiovascular disease (CVD). Indeed, several studies report an increased incidence of atherosclerotic CVD after ICI administration, with the occurrence of pathologies such as myocardial infarction, ischemic stroke and coronary artery disease significantly higher after ICI use. Increased awareness and better monitoring of ICI-treated patients can elucidate risk factors that contribute to ICI-induced aggravation of atherosclerosis and identify promising treatment strategies. For now, optimal cardiovascular risk assessment is required to protect ICI-receiving patients and long-term survivors of cancer from the detrimental effects of ICI therapy on atherosclerotic CVD.
Why musical hierarchies?
Authors: Courtney B. Hilton, Rie Asano, Cedric Boeckx
Journal: Behavioral and Brain Sciences (2021)

Abstract Credible signaling may have provided a selection pressure for producing and discriminating increasingly elaborate proto-musical signals. But, why evolve them to have hierarchical structure? We argue that the hierarchality of tonality and meter is a byproduct of domain-general mechanisms evolved for reasons other than credible signaling.