tbuckley/cabot-search huggingface dataset:
Abstract 303: C/ebpβ Plays a Crucial Role in Protecting the Heart From Ischemic Injury Through its Phosphorylation at Thr299
Authors: Jihoon Nah, Yasuhiro Maejima, Peiyong Zhai, Narayani Nagarajan, Junichi Sadoshima
Journal: Circulation Research (2017)

CCAAT-enhancer-binding protein (C/EBP)β is a basic-leucine zipper transcription factor family member that regulates various cellular mechanisms, including cell differentiation, proliferation, cell death and survival, and inflammation. Post-translational modifications of C/EBPβ, such as phosphorylation, acetylation, and SUMOylation, play an important role in regulating the function of C/EBPβ under stress conditions. However, the function of C/EBPβ in cardiomyocytes is not fully understood. Here, we investigated the role of C/EBPβ in the heart under stress. C/EBPβ is phosphorylated at Thr299 in response to oxidative stress in cardiomyocytes in vitro and Mst1, a serine/threonine kinase, mediates this phosphorylation. C/EBPβ is also phosphorylated at Thr299 in the heart during three-hour myocardial ischemia. Overexpression of C/EBPβ and its phosphomimetic mutant (T299E) increases expression of antioxidant-genes, including catalase and MnSOD, and decreases pro-apoptotic genes, such as NOXA, in cardiomyocytes. To elucidate the role of phosphorylation of C/EBPβ at Thr299 in mediating cardiac function during cardiac stress, we generated C/EBPβ-T250E knock-in mice (Thr250 in mice corresponds to Thr299 in humans). C/EBPβ-T250E knock-in mice are born with a normal Mendelian ratio and no apparent basal phenotype. However, similar to the findings in cardiomyocytes, heterozygous C/EBPβ-T250E knock-in mice showed increased expression of anti-oxidant genes, including catalase (1.93±1.0-fold vs. wild-type mice) and MnSOD (5.93±3.24-fold vs. wild-type mice), in the heart at baseline. Moreover, heterozygous C/EBPβ-T250E knock-in mice showed protective effects against three-hour ischemia (% infarct size per AAR: 39.88±3.25 vs. 32.90±2.79). These results indicate that phosphorylation of C/EBPβ at Thr299 plays a crucial role in protecting the heart during ischemic injury by regulating both antioxidant and pro-apoptotic gene expression.
The preventive strategy for pandemics in the elderly is to collect in advance samples &amp; data to counteract chronic inflammation (inflammaging)
Authors: Georg Fuellen, Oliver Liesenfeld, Axel Kowald, Israel Barrantes, Manuela Bastian, Andreas Simm, Ludger Jansen, Alexander Tietz-Latza, Dagmar Quandt, Claudio Franceschi, Michael Walter
Journal: Ageing Research Reviews (2020)
Abstract 12012: Maltohexaose-indocyanine Green (mh-icg) for Near Infrared Imaging of Bacterial Endocarditis
Authors: Kiyoko Takemiya, Joachim J Roeise, Maomao He, Chung Taing, Alexander G Rodriguez, Niren Murthy, Mark M Goodman, W Robert R Taylor
Journal: Circulation (2019)

Background: Early diagnosis of endocarditis has been a clinical challenge, especially with prosthetic valve endocarditis. We have previously shown that maltodextrin-based imaging probes are interna...
Heterogenous Populations of Tissue-Resident CD8+ T Cells Are Generated in Response to Infection and Malignancy
Authors: J. Justin Milner, Clara Toma, Zhaoren He, Nadia S. Kurd, Quynh P. Nguyen, Bryan McDonald, Lauren Quezada, Christella E. Widjaja, Deborah A. Witherden, John T. Crowl, Laura A. Shaw, Gene W. Yeo, John T. Chang, Kyla D. Omilusik, Ananda W. Goldrath
Journal: Immunity (2020)
138O CNS metastases in HER2-positive metastatic breast cancer treated with trastuzumab deruxtecan: DESTINY-Breast01 subgroup analyses
Authors: G. Jerusalem, Y.H. Park, T. Yamashita, S.A. Hurvitz, S. Chen, J. Cathcart, C. Lee, C. Perrin
Journal: Annals of Oncology (2020)
A phase II, randomized, double‐blind, placebo‐controlled, dose‐ranging study to evaluate the efficacy and safety of VT‐1161 oral tablets in the treatment of patients with distal and lateral subungual onychomycosis of the toenail*
Authors: B. Elewski, S. Brand, T. Degenhardt, S. Curelop, R. Pollak, R. Schotzinger, A. Tavakkol, Javier Alonso‐Llamazares, Scott J. Ashton, Neal Bhatia, Michael Billings, Andrew Blauvelt, Norman Bystol, Brandt Dodson, Michael H. Gold, Kimberly Grande, Michael Jarratt, Terry S. Jones, Maria A. Kasper, Steven E. Kempers, Brock McConnehey, Michael Noss, David Pariser, Lawrence Parish, Phoebe Rich, Joseph Ahmad Samady, Joel Schlessinger, Doug Schumacher, Kenneth Stein, Cynthia Strout, Eduardo Tschen, John H. Tu, Max Weisfeld
Journal: British Journal of Dermatology (2020)

Onychomycosis is a fungal disease that affects the fingernails and toenails and is predominantly caused by dermatophytes. VT-1161 is a novel inhibitor of fungal CYP51 through the inhibition of lanosterol demethylase, and has demonstrated potent activity against Trichophyton rubrum and Trichophyton mentagrophytes.To evaluate the safety and efficacy of four dosing regimens of orally administered VT-1161 compared with placebo in patients with moderate-to-severe distal and lateral subungual onychomycosis of the toenail.This was a phase II, randomized, double-blind, placebo-controlled, multicentre study (ClinicalTrials.gov identifier NCT02267356). Patients aged 18-70 years (n = 259) who had 25-75% mycotic involvement were randomized to five treatment groups. They received 300 mg VT-1161 as a 2-week daily dose, followed by a once-weekly dose for either 10 or 22 weeks, or 600 mg VT-1161 as a 2-week daily dose, followed by a once-weekly dose for either 10 or 22 weeks. All treatments were followed by a nontreatment period of 36 weeks. A matching placebo arm was included.In the intent-to-treat population, at week 48 the complete cure rates were 0% in the placebo group and ranged from 32% to 42% in the VT-1161 treatment groups (P < 0·001 vs. placebo). VT-1161 was well tolerated, with no evidence of an adverse effect on liver function or QT intervals.VT-1161 treatment led to high nail clearance rates and a favourable safety profile. VT-1161 exhibits characteristics that appear promising for the treatment of this chronic and difficult-to-treat condition and warrants further evaluation in larger studies.
104P Cost and healthcare resource utilization (HCRU) for patients receiving neoadjuvant therapy for early-stage triple-negative breast cancer (ESTNBC)
Authors: W.C. Rhodes, S. Gautam, A. Haiderali, M. Huang, J. Sieluk, K.E. Skinner, L.S. Schwartzberg
Journal: Annals of Oncology (2020)
CERVICAL CORD INJURY
Authors: H P AIDEM, L D BAKER
Journal: JAMA (1964)

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Firearm-Related Injury and Death: A U.S. Health Care Crisis in Need of Health Care Professionals
Authors: Darren B. Taichman, Howard Bauchner, Jeffrey M. Drazen, Christine Laine, Larry Peiperl
Journal: PLoS Medicine (2017)

What would happen if on one day more than 50 people died and over 10 times that many were harmed by an infectious disease in the United States?Likely, our nation's esteemed and highly capable public health infrastructure would gear up to care for those harmed and study the problem.There would be a rush to identify the cause, develop interventions, and refine them continually until the threat is eliminated or at least contained.In light of the risks to public health (after all, over 500 people have been harmed already!), health care professionals would sound the alarm.We would demand funding.We would go to conferences to learn what is known and what we should do.We would form committees at our institutions to plan local responses to protect our communities.The United States would spend millions or more in short order to assure public safety, and no elected officials would conceive of getting in the way.Rather, they would compete to be calling the loudest for the funds and focus required to protect our people.Americans should be proud of our prowess at and commitment to addressing public health crises.Yet, here we are again with another editorial about the public health crisis of firearm-related injury and death following what used to be unthinkable, this time a mass murder and casualties at a concert in Las Vegas.We've written it all before.The staggering numbers killed annually.The numbers left permanently disabled.The families left to cope with the loss of loved ones or to care for those broken but not killed by a bullet.As health care professionals, we seem powerless.This public health crisis seems beyond the reach of our tools.Is there really nothing health care professionals can do?We think there is a lot.We need to each ask ourselves what we have done to apply our knowledge and skills to help address the problem since the moment of silence that followed the last mass shooting.More silence is not the answer.Have we demanded funding to adequately study the problem and test solutions?Have we participated in such studies?Have we mobilized forces at our institutions to plan strategies to lower the risks in our communities?Have we talked to our patients about gun safety and effectively challenged policies that would enforce our silence on this matter?Some of our colleagues have.We should be proud of them, but they need all of our help.And so do our patients.Here's a short list of how health care professionals can use our skills and voices to fight the threat that firearms present to health in the United States.Educate yourself.Read the background materials and proposals for sensible firearm legislation from health care professional organizations.
An Eclectic Cast of Cellular Actors Orchestrates Innate Immune Responses in the Mechanisms Driving Obesity and Metabolic Perturbation
Authors: Lakshmi Arivazhagan, Henry H. Ruiz, Robin A. Wilson, Michaele B. Manigrasso, Paul F. Gugger, Edward A. Fisher, Kathryn J. Moore, Ravichandran Ramasamy, Ann Marie Schmidt
Journal: Circulation Research (2020)

The escalating problem of obesity and its multiple metabolic and cardiovascular complications threatens the health and longevity of humans throughout the world. The cause of obesity and one of its chief complications, insulin resistance, involves the participation of multiple distinct organs and cell types. From the brain to the periphery, cell-intrinsic and intercellular networks converge to stimulate and propagate increases in body mass and adiposity, as well as disturbances of insulin sensitivity. This review focuses on the roles of the cadre of innate immune cells, both those that are resident in metabolic organs and those that are recruited into these organs in response to cues elicited by stressors such as overnutrition and reduced physical activity. Beyond the typical cast of innate immune characters invoked in the mechanisms of metabolic perturbation in these settings, such as neutrophils and monocytes/macrophages, these actors are joined by bone marrow-derived cells, such as eosinophils and mast cells and the intriguing innate lymphoid cells, which are present in the circulation and in metabolic organ depots. Upon high-fat feeding or reduced physical activity, phenotypic modulation of the cast of plastic innate immune cells ensues, leading to the production of mediators that affect inflammation, lipid handling, and metabolic signaling. Furthermore, their consequent interactions with adaptive immune cells, including myriad T-cell and B-cell subsets, compound these complexities. Notably, many of these innate immune cell-elicited signals in overnutrition may be modulated by weight loss, such as that induced by bariatric surgery. Recently, exciting insights into the biology and pathobiology of these cell type-specific niches are being uncovered by state-of-the-art techniques such as single-cell RNA-sequencing. This review considers the evolution of this field of research on innate immunity in obesity and metabolic perturbation, as well as future directions.
Abstract 16214: Quantification of Viscoelastic Properties of Porcine Myocardium Extracellular Matrix
Authors: Nicolas Gallo, Gene Kim, Nir Uriel, John Georgiadis, Marcella K Vaicik
Journal: Circulation (2018)

Introduction: In failing myocardium, cardiac tissue remodels and can result in changes in composition, structure, and function. Myocardial extracellular matrix (ECM) plays an important role in remo...
iTRAQ‐based proteomic analysis reveals potential serum biomarkers of allergic and nonallergic asthma
Authors: Juan José Nieto‐Fontarigo, Francisco Javier González‐Barcala, Luis Juan Andrade‐Bulos, María Esther San‐José, María Jesús Cruz, Luis Valdés‐Cuadrado, Rosa María Crujeiras, Pilar Arias, Francisco Javier Salgado
Journal: Allergy (2020)

Abstract Background Asthma is heterogeneous disease with different phenotypes, endotypes and severities. Definition of these subgroups requires the identification of biomarkers in biological samples, and serum proteomics is a useful and minimally invasive method for this purpose. Therefore, the aim of this study was to detect serum proteins whose abundance is distinctively associated with different asthma phenotypes (allergic vs nonallergic) or severities. Methods For each group of donors (32 healthy controls, 43 allergic rhinitis patients and 192 asthmatics with different phenotypes and severities), we generated two pools of sera that were analysed by a shotgun MS approach based on combinatorial peptide ligand libraries and iTRAQ‐LC‐MS/MS. Results MS analyses identified 18 proteins with a differential abundance. Functional/network study of these proteins identified key processes for asthma pathogenesis, such as complement activation, extracellular matrix organization, platelet activation and degranulation, or post‐translational protein phosphorylation. Furthermore, our results highlighted an enrichment of the “ Regulation of Insulin‐like Growth Factor (IGF) transport and uptake by Insulin‐like Growth Factor Binding Proteins (IGFBPs) ” route in allergic asthma and the lectin pathway of complement activation in nonallergic asthma. Thus, several proteins (eg IGFALS, HSPG2, FCN2 or MASP1) displayed a differential abundance between the different groups of donors. Particularly, our results revealed IGFALS as a useful biomarker for moderate‐severe allergic asthma. Conclusion Our data suggest a set of serum biomarkers, especially IGFALS, capable of differentiating allergic from nonallergic asthma. These proteins reveal different pathophysiological mechanisms and may be useful in the future for diagnosis, prognosis or targeted therapy purposes.
Hormone Replacement Therapy and the Risk for First Hip Fracture
Authors: Tord Naessén, Ingemar Persson, Hans-Olov Adami, Reinhold Bergström, Leif Bergkvist
Journal: Annals of Internal Medicine (2020)

Abstract Objective:To determine the relative risk for sustaining a first hip fracture after hormone replacement therapy. Design:Prospective population-based cohort study with an average observation...
Reactive cutaneous capillary endothelial proliferation in advanced hepatocellular carcinoma patients treated with camrelizumab: data derived from a multicenter phase 2 trial
Authors: Feng Wang, Shukui Qin, Xinchen Sun, Zhenggang Ren, Zhiqiang Meng, Zhendong Chen, Xiaoli Chai, Jianping Xiong, Yuxian Bai, Lin Yang, Hong Zhu, Weijia Fang, Xiaoyan Lin, Xiaoming Chen, Enxiao Li, Linna Wang, Ping Yan, Jianjun Zou
Journal: Journal of Hematology & Oncology (2020)

Abstract Background Association of immune-related adverse events with tumor response has been reported. Reactive cutaneous capillary endothelial proliferation (RCCEP) is the most common adverse event related to camrelizumab, an immune checkpoint inhibitor, but lack of comprehensive analyses. In this study, we conducted comprehensive analyses on RCCEP in advanced hepatocellular carcinoma (HCC) patients treated with camrelizumab monotherapy. Methods Data were derived from a Chinese nationwide, multicenter phase 2 trial of camrelizumab in pre-treated advanced HCC. The occurrence, clinicopathological characteristics, and prognostic value of RCCEP were analyzed. Results With a median follow-up of 12.5 months, 145 of the 217 camrelizumab-treated patients (66.8%) experienced RCCEP (all grade 1 or 2). RCCEP occurred on the skin surface, mainly on the skin surface of head, face, and trunk. RCCEP could be divided into 5 types including “red-nevus-like,” “pearl-like,” “mulberry-like,” “patch-like,” and “tumor-like,” according to the morphological features. RCCEP biopsy and pathology showed capillary endothelial hyperplasia and capillary hyperplasia in dermis. Significant association between RCCEP occurrence with higher objective response rate was observed (19.3% vs. 5.6%; one-sided p = 0.0044). Compared with those without RCCEP, patients with RCCEP had prolonged progression-free survival (median PFS; 3.2 months vs. 1.9 months; one-sided p &lt; 0.0001) and overall survival (median OS; 17.0 months vs. 5.8 months; one-sided p &lt; 0.0001). In multivariable analyses, the development of RCCEP was significantly associated with prolonged PFS and OS after adjusting for baseline covariates. In addition, the landmark analyses of PFS and OS were consistent with the unadjusted analysis. Conclusions RCCEP occurred on the skin surface and was an immune response of skin capillary endothelial cells. RCCEP occurrence positively associated with outcomes of camrelizumab in advanced HCC.
Collateral Toxicity Limits the Evolution of Bacterial Release Factor 2 toward Total Omnipotence
Authors: Hind Abdalaal, Shreya Pundir, Xueliang Ge, Suparna Sanyal, Joakim Näsvall
Journal: Molecular Biology and Evolution (2020)

Abstract When new genes evolve through modification of existing genes, there are often tradeoffs between the new and original functions, making gene duplication and amplification necessary to buffer deleterious effects on the original function. We have used experimental evolution of a bacterial strain lacking peptide release factor 1 (RF1) in order to study how peptide release factor 2 (RF2) evolves to compensate the loss of RF1. As expected, amplification of the RF2-encoding gene prfB to high copy number was a rapid initial response, followed by the appearance of mutations in RF2 and other components of the translation machinery. Characterization of the evolved RF2 variants by their effects on bacterial growth rate, reporter gene expression, and in vitro translation termination reveals a complex picture of reduced discrimination between the cognate and near-cognate stop codons and highlights a functional tradeoff that we term “collateral toxicity.” We suggest that this type of tradeoff may be a more serious obstacle in new gene evolution than the more commonly discussed evolutionary tradeoffs between “old” and “new” functions of a gene, as it cannot be overcome by gene copy number changes. Further, we suggest a model for how RF2 autoregulation responds to alterations in the demand not only for RF2 activity but also for RF1 activity.
Diagnostic dilemma of perioperative myocardial infarction after coronary artery bypass grafting: A review
Authors: Viola Weidenmann, N. Bryce Robinson, Lisa Q. Rong, Irbaz Hameed, Ajita Naik, Mahmoud Morsi, Philippe Grieshaber, Andreas Böning, Leonard N. Girardi, Mario Gaudino
Journal: International Journal of Surgery (2020)
Phenotypic and functional translation of IL33 genetics in asthma
Authors: Maria E. Ketelaar, Michael A. Portelli, F. Nicole Dijk, Nick Shrine, Alen Faiz, Cornelis J. Vermeulen, Cheng J. Xu, Jenny Hankinson, Sangita Bhaker, Amanda P. Henry, Charlote K. Billington, Dominick E. Shaw, Simon R. Johnson, Andrew V. Benest, Vincent Pang, David O. Bates, Z.E.K. Pogson, Andrew Fogarty, Tricia M. McKeever, Amisha Singapuri, Liam G. Heaney, Adel H. Mansur, Rekha Chaudhuri, Neil C. Thomson, John W. Holloway, Gabrielle A. Lockett, Peter H. Howarth, Robert Niven, Angela Simpson, Martin D. Tobin, Ian P. Hall, Louise V. Wain, John D. Blakey, Christopher E. Brightling, Ma'en Obeidat, Don D. Sin, David C. Nickle, Yohan Bossé, Judith M. Vonk, Maarten van den Berge, Gerard H. Koppelman, Ian Sayers, Martijn C. Nawijn
Journal: Journal of Allergy and Clinical Immunology (2020)
Role of Ambulatory and Home Blood Pressure Monitoring in Clinical Practice
Authors: Daichi Shimbo, Marwah Abdalla, Louise Falzon, Raymond R. Townsend, Paul Muntner
Journal: Annals of Internal Medicine (2015)

This review describes ambulatory blood pressure monitoring (ABPM) and home blood pressure monitoring (HBPM), the blood pressure phenotypic measurements that can be ascertained, and the evidence tha...
Baldness and myocardial infarction
Authors: B. Kleinmuntz
Journal: JAMA (1993)

<h3>In Reply.</h3> —There are inaccuracies in Dr Kleinmuntz's letter, and he appears not to understand case-control methods. The 218 men with gastrointestinal disorders were not excluded at all: they were included (as controls). As was stated in the article, men (cases and controls) with a history of rheumatic heart disease, cardiomyopathy, or prior cardiac surgery were not eligible. Only men with a first MI who were under 55 years of age were included as cases; none had preexisting congestive heart failure. In addition, history of angina pectoris was controlled for in the analysis. Ninety-five percent CIs are commonly used in reporting results of epidemiologic studies and are compatible with the conventional definition of statistical significance (<i>P</i>&lt;.05). The<i>P</i>value of &lt;.01 was derived from a test for trend and had nothing to do with the estimation of CIs. With regard to Kleinmuntz's remaining comments, we stated that our nurse-interviewers