tbuckley/cabot-search huggingface dataset:
<i>S</i> -Nitrosoglutathione Reductase Is Essential for Protecting the Female Heart From Ischemia-Reperfusion Injury
Authors: Kevin M. Casin, Jonathan Fallica, Nathan Mackowski, Ryne J. Veenema, Ashley Chan, Amanda St. Paul, Guangshuo Zhu, Djahida Bedja, Shyam Biswal, Mark J. Kohr
Journal: Circulation Research (2018)

Protein S-nitros(yl)ation (SNO) has been implicated as an essential mediator of nitric oxide-dependent cardioprotection. Compared with males, female hearts exhibit higher baseline levels of protein SNO and associated with this, reduced susceptibility to myocardial ischemia-reperfusion injury. Female hearts also exhibit enhanced S-nitrosoglutathione reductase (GSNO-R) activity, which would typically favor decreased SNO levels as GSNO-R mediates SNO catabolism. Because female hearts exhibit higher SNO levels, we hypothesized that GSNO-R is an essential component of sex-dependent cardioprotection in females. Male and female wild-type mouse hearts were subjected to ex vivo ischemia-reperfusion injury with or without GSNO-R inhibition (N6022). Control female hearts exhibited enhanced functional recovery and decreased infarct size versus control males. Interestingly, GSNO-R inhibition reversed this sex disparity, significantly reducing injury in male hearts, and exacerbating injury in females. Similar results were obtained with male and female GSNO-R-/- hearts using ex vivo and in vivo models of ischemia-reperfusion injury. Assessment of SNO levels using SNO-resin assisted capture revealed an increase in total SNO levels with GSNO-R inhibition in males, whereas total SNO levels remained unchanged in females. However, we found that although GSNO-R inhibition significantly increased SNO at the cardioprotective Cys39 residue of nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 3 in males, SNO-NADH dehydrogenase subunit 3 levels were surprisingly reduced in N6022-treated female hearts. Because GSNO-R also acts as a formaldehyde dehydrogenase, we examined postischemic formaldehyde levels and found that they were nearly 2-fold higher in N6022-treated female hearts compared with nontreated hearts. Importantly, the mitochondrial aldehyde dehydrogenase 2 activator, Alda-1, rescued the phenotype in GSNO-R-/- female hearts, significantly reducing infarct size. These striking findings point to GSNO-R as a critical sex-dependent mediator of myocardial protein SNO and formaldehyde levels and further suggest that different therapeutic strategies may be required to combat ischemic heart disease in males and females.
Patient Attitudes Toward Individualized Recommendations to Stop Low-Value Colorectal Cancer Screening
Authors: Marc S. Piper, Jennifer K. Maratt, Brian J. Zikmund-Fisher, Carmen Lewis, Jane Forman, Sandeep Vijan, Valbona Metko, Sameer D. Saini
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Guidelines for colorectal cancer (CRC) screening recommend an individualized approach in older adults that is informed by consideration of life expectancy and cancer risk. However, little is known about how patients perceive individualized screening recommendations. <h3>Objective</h3> To assess veterans' attitudes toward and comfort with cessation of low-value CRC screening (defined as screening in a patient for whom the benefit is expected to be small based on quantitative estimates from hypothetical risk calculators). <h3>Design, Setting, and Participants</h3> This survey study included patients older than 50 years who had undergone prior screening colonoscopy with normal results at the Veterans Affairs Ann Arbor Healthcare System. A total of 1500 surveys were mailed to potential participants from November 1, 2010, to January 1, 2012. Survey data were analyzed from January 1, 2016, to December 31, 2017. <h3>Main Outcomes and Measures</h3> Response to the question, "If you personally had serious health problems that were likely to shorten your life and your doctor did not think screening would be of much benefit based on the calculator, how comfortable would you be with not getting any more screening colonoscopies?" <h3>Results</h3> Of the 1500 surveys mailed, 85 were returned to sender, leaving 1415 potential respondents; 1054 of these respondents (median age range, 60-69 years; 884 [85.9%] white and 965 [94.2%] male) completed the survey (response rate, 74.5%). A total of 300 (28.7%) were not at all comfortable with cessation of low-value CRC screening, and 509 (49.3%) thought that age should never be used to decide when to stop screening. In addition, 332 (31.7%) thought it was not at all reasonable to use life expectancy calculators, and 255 (24.3%) thought it was not at all reasonable to use CRC risk calculators to guide these decisions. In ordered logistic regression analysis, factors associated with more comfort with screening cessation were (1) higher trust in physician (odds ratio [OR], 1.19; 95% CI, 1.07-1.32), (2) higher perceived health status (OR, 1.41; 95% CI, 1.23-1.61), and (3) higher barriers to screening (OR, 1.20; 95% CI, 1.11-1.30). Factors that were associated with less comfort with screening cessation included (1) greater perceived effectiveness of screening (OR, 0.86; 95% CI, 0.80-0.94) and (2) greater perceived threat of CRC (OR, 0.81; 95% CI, 0.73-0.89). <h3>Conclusions and Relevance</h3> The findings suggest that many veterans have strong preferences against screening cessation even when given detailed information about why the benefit may be low. Efforts to tailor screening recommendations may be met by resistance unless they are accompanied by efforts to address underlying perceptions about the benefit of screening.
Abstract 19898: In-vitro Assessment of Coronary Hemodynamics in 3D Printed Patient-specific Geometry
Authors: Guanglei Xiong, Kranthi Kolli, Hilary A Soohoo, James K Min
Journal: Circulation (2015)

Introduction: Recent advances in cardiac imaging permit detailed assessment of myocardial perfusion using Single Photon Emission Computed Tomography and integrated evaluation of coronary anatomy and myocardial perfusion using Computed Tomography [CT]. However, neither technique is adequate to evaluate coronary physiology on a per-vessel level, limiting diagnostic accuracy compared to invasive physiologic gold standards, e.g. fractional flow reserve (FFR). Recently, computational fluid dynamics (CFD) applied to CT imaging offers per-vessel hemodynamic analysis and has been shown to improve the diagnostic performance over CT alone compared to invasive FFR. In this study, we developed an alternative in-vitro method to quantify coronary hemodynamics in a 3D printed patient-specific geometry, replicating in-vivo physiologic conditions. Hypothesis: Our approach overcome inevitable numerical assumptions (rigid walls and unrealistic boundary conditions) made in CFD and can potentially lead to a more favorable diagnostic performance. Methods: In Figure 1, patient-specific replica was fabricated from segmented coronary arteries using high-resolution 3D printing. It was used to examine the hemodynamic variables (velocity, pressure and FFR) by a flow circulation system including a programmable flow pump, tunable flow impedances, pressure sensors, and particle image velocimetry. Results: Our initial experiments demonstrated the concordance of our in-vitro results to in in-vivo measurements. Instead of interrogating only one flow condition in CFD, our system allows for assessment of a given coronary lesion under a range of flow conditions from rest to maximal stress at no additional effort after initial setup. Conclusions: We expect our approach will provide a new competitive way to identify coronary lesion, and more importantly, the flow condition under which a given lesion becomes hemodynamically significant.
Abstract 17849: Association of Obstructive Sleep Apnea With Endothelial Dysfunction, Arterial Stiffness, and Markers of Subclinical Atherosclerosis
Authors: Daniel Shpilsky, Oluremi Ajala, Sebhat Erqou, Oladipupo Olafiranye, Kevin Kip, Aryan Aiyer, Steven Reis
Journal: Circulation (2016)

Introduction: Studies have reported associations between obstructive sleep apnea (OSA) and cardiovascular disease (CVD) outcomes. Proposed mechanisms include endothelial dysfunction and increased a...
Low-Dose Budesonide/Formoterol Counteracts Airway Inflammation and Improves Lung Function in Chronic Obstructive Pulmonary Disease
Authors: Amir Hakim, Younis Khan, Ignacio Esteban, Sally Meah, Anna Miller-Larsson, Peter J. Barnes, Omar S. Usmani
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Contribution of bone marrow-derived cells to in situ engineered tissue capsules in a rat model of chronic kidney disease
Authors: Taisiya Bezhaeva, Wouter J. Geelhoed, Dong Wang, Haoyong Yuan, Eric P. van der Veer, Carla M.A. van Alem, Febriyani F.R. Damanik, Xuefeng Qiu, Anton-Jan van Zonneveld, Lorenzo Moroni, Song Li, Joris I. Rotmans
Journal: Biomaterials (2018)
5‐Hydroxytryptamine Receptor 1D Aggravates Hepatocellular Carcinoma Progression Through FoxO6 in AKT‐Dependent and Independent Manners
Authors: Xueliang Zuo, Zhiqiang Chen, Juan Cai, Wen Gao, Yao Zhang, Guoyong Han, Liyong Pu, Zhengshan Wu, Wei You, Jianjie Qin, Xinzheng Dai, Hongbing Shen, Jindao Wu, Xuehao Wang
Journal: Hepatology (2018)

Serotonin and its receptors have been shown to play critical regulatory roles in cancer biology. Nevertheless, the contributions of 5‐hydroxytryptamine 1D (5‐HT1D), an indispensable member of the serotonergic system, to hepatocellular carcinoma (HCC) remain unknown. The present study demonstrated that the 5‐HT1D expression level was significantly up‐regulated in HCC tissues and cell lines. The 5‐HT1D expression level was closely correlated with unfavorable clinicopathological characteristics. Survival analyses show that elevated 5‐HT1D expression level predicts poor overall survival and high recurrence probability in HCC patients. Functional studies revealed that 5‐HT1D significantly promoted HCC proliferation, epithelial‐mesenchymal transition, and metastasis in vitro and in vivo . Mechanistically, 5‐HT1D could stabilize PIK3R1 by inhibiting its ubiquitin‐mediated degradation. The interaction between 5‐HT1D and phosphoinositide‐3‐kinase regulatory subunit 1 (PIK3R1) enhanced the expression of FoxO6 through the PI3K/Akt signaling pathway; FoxO6 could also be directly transcriptionally activated by 5‐HT1D in an Akt‐independent manner. MicroRNA‐599 was found to be an upstream suppressive modulator of 5‐HT1D. Additionally, 5‐HT1D could attenuate tryptophan hydroxylase 1 expression through the PI3K/Akt/cut‐like homeobox 1 axis in HCC. Conclusion : Herein, we uncovered the potent oncogenic effect of 5‐HT1D on HCC by interacting with PIK3R1 to activate the PI3K/Akt/FoxO6 pathway, and provided a potential therapeutic target for HCC.
Abstract 16350: Regulation of Gene Expression in Human Induced Pluripotent Stem Cell-derived Cardiomyocytes Using Magnetic Nanoparticles
Authors: Megan A Yamoah, Padmini Sirish, Janhavi Sharma, Wei Chun Chen, Jeong-Han Lee, Karen S Chavez, Wenying Wang, Deborah K Lieu, Javier E López, Xiaodong Zhang
Journal: Circulation (2015)

Background. Delivery of transgenes into human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) represents an important tool in cardiac regeneration and has potential for clinical applications. Gene transfection into hiPSC and hiPSC-CMs, however, is more difficult than for somatic cells. Despite multiple other methods (i.e. nucleofection, lipofectamine, and viral-based transduction), efficiency, cytotoxicity, safety and cost remain unsatisfactory. Increasingly, nanoparticles (NPs) have been used in biomedical research as a powerful tool in drug delivery and personalized medicine. The objective of this study is to examine the regulation of gene expression in hiPSC and hiPSC-CMs using magnetic NPs. Methods and Results. HiPSCs and hiPSC-CMs were transfected using magnetic NPs. Confocal microscopy and flow cytometry confirmed and quantitated the transfection efficiency. Enhanced green fluorescence protein (eGFP) and eGFP-fused membrane proteins served as positive controls. We compared the transfection efficiency of hiPSCs with that of human embryonic kidney cells (HEK 293). We observed that the averaged efficiency in hiPSCs is 43 ± 2 % compared to that of 62 ± 4% in HEK 293. Further analysis of the transfected hiPSCs showed that the pluripotency is not altered by NPs. NPs were also used to direct cardiac differentiation using cardiomyocyte-specific transcription factors. Finally, robust transfection of hiPSC-CMs was obtained using NPs to direct the expression of small-conductance Ca 2+ -activated K + (SK) channels. Patch-clamp recordings demonstrated successful maturation of hiPSC-CMs with respect to the resting membrane potentials and spontaneous action potentials. Conclusion. The difficult-to-transfect hiPSCs and hiPSC-CMs were efficiently transfected using magnetic NPs. Our study offers an enhanced approach to direct cardiac differentiation and maturation of hiPSC-CMs without the need for viral vector generation. Funded by AHA (14BGIA18870087 to XZ), NIH K12 (#UL1 TR000002 to JEL) and Harold Amos Medical Faculty Development Program, RWJ Foundation (to JEL), and California Institute of Regenerative Medicine (CIRM, RB4-05764 to DKL), and Fellowship Awards to PS and JS from CIRM Training Program to UC Davis.
Atherosclerotic Conditions Promote the Packaging of Functional MicroRNA-92a-3p Into Endothelial Microvesicles
Authors: Yangyang Liu, Qian Li, Mohammed Rabiul Hosen, Andreas Zietzer, Anna Flender, Paula Levermann, Theresa Schmitz, Daniel Frühwald, Philip Goody, Georg Nickenig, Nikos Werner, Felix Jansen
Journal: Circulation Research (2019)

Rationale: Microvesicle-incorporated microRNAs (miRs) are biomarkers and effectors of cardiovascular disease. Whether microvesicle-miR expression is regulated in coronary artery disease (CAD) or not is unknown. Objective: Here, we explore the expression of circulating microvesicle-miRs in patients with CAD and investigate the role of microvesicle-miR in endothelial cells. Methods and Results: Circulating microvesicles were isolated from patients’ plasma by using ultracentrifugation. Electron microscopy was used to determine the size of the microvesicles. A Taqman miR array revealed certain microvesicle-miRs are significantly regulated in patients with stable CAD compared with patients with ACS. To validate the miR array results, 180 patients with angiographically excluded CAD (n=41), stable CAD (n=77), and acute coronary syndrome (n=62) were prospectively studied. Nine miRs involved in regulation of vascular performance—miR-126-3p, miR-222-3p, miR-let-7d-5p, miR-21-5p, miR-26a-5p, miR-92a-3p, miR-139-5p, miR-30b-5p, and miR-199a-5p—were quantified in circulating microvesicles by real-time polymerase chain reaction (PCR). Among these, miR-92a-3p was significantly increased in patients with CAD compared with non-CAD patients. Microvesicle-sorting experiments showed endothelial cells (ECs) were the major cell source for microvesicles containing miR-92a-3p. In vitro oxLDL (oxidized low-density lipoprotein) and IL-6 (interleukin-6) stimulation increased miR-92a-3p expression in parent ECs and upregulated the expression level of endothelial microvesicle (EMV)-incorporated miR-92a-3p. Labeling of miR-92a-3p and EMVs demonstrated that functional miR-92a-3p was transported into recipient ECs, which accelerated cell migration and proliferation. Knockdown of miR-92a-3p in EMVs abrogated EMV-mediated effects on EC migration, proliferation, and blocked vascular network formation in a matrigel plug. Polymerase chain reaction–based gene profiling showed that the expression of THBS1 (thrombospondin 1) protein—a target of miR-92a-3p and an inhibitor of angiogenesis—was significantly reduced in ECs by EMVs. Knockdown of miR-92a-3p in EMVs abrogated EMV-mediated inhibition of the THBS1 gene and protein expression. Conclusions: Atherosclerotic conditions promote the packaging of endothelial miR-92a-3p into EMVs. EMV-mediated transfer of functional miR-92a-3p regulates angiogenesis in recipient ECs by a THBS1-dependent mechanism.
Flow cytometry for fast screening and automated risk assessment in systemic light-chain amyloidosis
Authors: Noemi Puig, Bruno Paiva, Marta Lasa, Leire Burgos, Jose J. Perez, Juana Merino, Cristina Moreno, Maria-Belen Vidriales, Dolores Gómez Toboso, Maria-Teresa Cedena, Enrique M. Ocio, Ramon Lecumberri, Alfonso García de Coca, Jorge Labrador, Maria-Esther Gonzalez, Luis Palomera, Mercedes Gironella, Valentin Cabañas, Maria Casanova, Albert Oriol, Isabel Krsnik, Albert Pérez-Montaña, Javier de la Rubia, Jose-Enrique de la Puerta, Felipe de Arriba, Felipe Prosper, Joaquin Martinez-Lopez, Quentin Lecrevisse, Javier Verde, Maria-Victoria Mateos, Juan-Jose Lahuerta, Alberto Orfao, Jesús F. San Miguel
Journal: Leukemia (2018)
Abstract 18641: Predictors of Emergency Medical Personnel’s Decision to Transmit or Not to Transmit the Prehospital 12-Lead ECG of Patients With Suspected Acute Myocardial Infarction
Authors: Amber DeSantis, Parker Landis, Mohammad Alrawashdeh, Christian Martin-Gill, Clifton Callaway, Salah S Al-Zaiti
Journal: Circulation (2017)

Introduction: Transmitting the prehospital 12-lead ECG has been shown to tremendously improve outcomes in patients with myocardial infarction (MI). Yet emergency personnel do not routinely transmit the 12-lead ECG to receiving facilities despite the availability of ECG acquisition and transmission capabilities. We sought to describe the behavior and predictors of emergency personnel’s decision to transmit or not to transmit the prehospital ECG of patients with suspected MI. Methods: This was a prospective, observational, cohort study that enrolled consecutive chest pain patients transported by Emergency Medical Services to participating UPMC facilities in Pittsburgh between 2013 and 2014. Prehospital and inhospital clinical data elements were collected from charts. The presence of MI was defined according to the universal definition of MI (detection of cardiac biomarkers plus evidence of ischemia). Paramedics’ impression of initial ECG was categorized as: normal sinus rhythm, ischemic ST changes, arrhythm...
Adrenomedullin Induces Cardiac Lymphangiogenesis After Myocardial Infarction and Regulates Cardiac Edema Via Connexin 43
Authors: Claire E. Trincot, Wenjing Xu, Hua Zhang, Molly R. Kulikauskas, Thomas G. Caranasos, Brian C. Jensen, Amélie Sabine, Tatiana V. Petrova, Kathleen M. Caron
Journal: Circulation Research (2019)

Cardiac lymphangiogenesis contributes to the reparative process post-myocardial infarction, but the factors and mechanisms regulating it are not well understood.To determine if epicardial-secreted factor AM (adrenomedullin; Adm=gene) improves cardiac lymphangiogenesis post-myocardial infarction via lateralization of Cx43 (connexin 43) in cardiac lymphatic vasculature.Firstly, we identified sex-dependent differences in cardiac lymphatic numbers in uninjured mice using light-sheet microscopy. Using a mouse model of Adm hi/hi ( Adm overexpression) and permanent left anterior descending ligation to induce myocardial infarction, we investigated cardiac lymphatic structure, growth, and function in injured murine hearts. Overexpression of Adm increased lymphangiogenesis and cardiac function post-myocardial infarction while suppressing cardiac edema and correlated with changes in Cx43 localization. Lymphatic function in response to AM treatment was attenuated in mice with a lymphatic-specific Cx43 deletion. In vitro experiments in cultured human lymphatic endothelial cells identified a novel mechanism to improve gap junction coupling by pharmaceutically targeting Cx43 with verapamil. Finally, we show that connexin protein expression in cardiac lymphatics is conserved between mouse and human.AM is an endogenous, epicardial-derived factor that drives reparative cardiac lymphangiogenesis and function via Cx43, and this represents a new therapeutic pathway for improving myocardial edema after injury.
Abstract 18978: Fractional Flow Reserve Derived From Coronary Computed Tomography Safely Defers Invasive Coronary Angiography in Patients With Stable Coronary Artery Disease
Authors: Mark G Rabbat, Brian Kauh, Ben Forrest, Souma Sengupta, Campbell Rogers, Khaled Dajani, Ari Goldberg, David Wilber, John Lopez
Journal: Circulation (2016)

Introduction: Fractional flow reserve (FFR) derived from coronary computed tomography datasets (FFRCT) has excellent accuracy to diagnose hemodynamically significant coronary artery disease (CAD) compared to invasive FFR as the reference standard. The recent PLATFORM Trial demonstrated that the use of FFRCT resulted in the safe cancellation of 61% of invasive coronary angiograms (ICA). In the United States, the real world feasibility of a diagnostic strategy using FFRCT is unknown. Thus, we sought to determine whether the use of a coronary computed tomography angiogram (CT) plus FFRCT guided strategy as compared to CT alone will reduce the rate of unnecessary ICA without increasing the occurrence of major cardiac events. Hypothesis: A combined CT/FFRCT guided diagnostic strategy will safely reduce the number of ICA compared to CT alone. Methods: 138 consecutive patients with suspected CAD referred for CT / FFRCT over a 9-month period without known CAD at Loyola University Chicago were included in the anal...
Mogamulizumab Monotherapy in the Treatment of Relapsed/Refractory Peripheral T-Cell Lymphoma or Cutaneous T-Cell Lymphoma Patients in Single-Institution Experience
Authors: Kazunori Murai, Hamada Hiroyuki, Akiyoshi Sato, Miyairi Yasuro, Yasuki Mori, Tsutomu Sakuma
Journal: Blood (2017)
The Evaluation of Residual Disease By Digital PCR, and TKI Duration Are Critical Predictive Factors for Molecular Recurrence after for Stopping Imatinib First-Line in Chronic Phase CML Patients: Results of the STIM2 Study.
Authors: Franck Emmanuel Nicolini, Stephanie Dulucq, Joelle Guilhot, Gabriel Etienne, Francois-Xavier Mahon
Journal: Blood (2018)
Urologic chronic pelvic pain syndrome: insights from the MAPP Research Network
Authors: J. Quentin Clemens, Chris Mullins, A. Lenore Ackerman, Tamara Bavendam, Adrie van Bokhoven, Benjamin M. Ellingson, Steven E. Harte, Jason J. Kutch, H. Henry Lai, Katherine T. Martucci, Robert Moldwin, Bruce D. Naliboff, Michel A. Pontari, Siobhan Sutcliffe, J. Richard Landis
Journal: Nature Reviews Urology (2018)
Black Lung Resurgence Raises New Challenges for Coal Country Physicians
Authors: Rebecca Voelker
Journal: JAMA (2018)

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