tbuckley/cabot-search huggingface dataset:
Lung-restricted inhibition of Janus kinase 1 is effective in rodent models of asthma
Authors: Hart S. Dengler, Xiumin Wu, Ivan Peng, Cornelia H. Rinderknecht, Youngsu Kwon, Eric Suto, Pawan Bir Kohli, Marya Liimatta, Kathy Barrett, Julia Lloyd, Gary Cain, Mike Briggs, Stephanie Addo, Gary Salmon, Savita Ubhayakar, Gauri Deshmukh, Sheerin K. Shahidi-Latham, Cristine M. Quiason-Huynh, Janet Jackman, John Liu, Nicholas C. Ray, Simon C. Goodacre, Adam Johnson, Brent S. McKenzie, Wyne P. Lee, Mark Zak, Jane R. Kenny, Nico Ghilardi
Journal: Science Translational Medicine (2018)

Inhalation of a Janus kinase 1 inhibitor suppressed lung inflammation without systemic side effects in rodent models of asthma.
Obstructive Sleep Apnea, Hypoxia, and Nonalcoholic Fatty Liver Disease
Authors: Omar A. Mesarwi, Rohit Loomba, Atul Malhotra
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Section:ChooseTop of pageAbstract <<Sleep-disordered Breathin...Mechanisms of Hypoxia-ind...Future DirectionsConclusionsReferencesCITING ARTICLES
Abstract 16488: Exploring the Functional Role of Exosomes in Stem Cell-mediated Cardiac Repair
Authors: Jennifer K Lang, Rebecca F Young, Hashmat Ashraf, John M Canty
Journal: Circulation (2015)

Numerous experimental and clinical studies have shown a beneficial effect of cardiosphere-derived cell (CDC) therapy on regeneration of injured myocardium. Paracrine signaling by CDC secreted exosomes is hypothesized to be the principal mediator of improved function, however the mechanism of exosome uptake, cell specificity, and information transfer has yet to be elucidated. Our aim was to define the role of physiologically secreted human CDC-derived exosomes on cardiac fibroblasts, endothelial cells and cardiomyocytes by employing a knockdown (KD) strategy against nSMase2 and Rab27a, two genes crucial in exosome secretion. Methods: Human CDCs (hCDCs) were grown from atrial tissue biopsy explant culture and characterized by flow cytometry and immunocytochemistry. CDC-derived exosomes were isolated and characterized by particle size, immunoblot analysis and electron microscopy. Protein concentration of exosome preparations was quantified by Bradford microassay. nSMase2 and Rab27a shRNAi lentivirus was generated and used to create stable CDC knockdown lines. Co-culture transwell in vitro assays were designed to assess target cell proliferation, migration, angiogenesis, and fibrotic gene expression. Results: hCDCs expressed CD105, CD90, GATA4 and Nkx2.5, and were CD45 and cardiac troponin T negative. hCDC-derived exosomes were immunoreactive for CD63 and HSP90 and negative for Cyctochrome c and EEA1. shRNAi KD of nSMase2 and Rab27a resulted in successful blockade of exosome release from hCDCs. HUVECs co-cultured with scrambled shRNAi CDCs versus shRNAi nSMase2 KD CDCs showed increased angiogenesis and migration without affecting proliferation. While TGF-β stimulation of human cardiac fibroblasts significantly increased collagen I (COLI) and collagen III (COLIII) gene expression, there was no significant decrease in COLI or COLIII after treatment with exosomes. Conclusions: Secretion of hCDC-derived exosomes was effectively inhibited by nSMase2 and Rab27a lentiviral KD. Exosome release contributed to the angiogenic and pro-migratory effects of hCDCs but did not play a role in the fibrotic gene expression of human cardiac fibroblasts, suggesting a role for physiological exosome secretion in stem cell-mediated cardiac repair.
High Frequency of the Ph-like PCB-ALL Subtype in Mexican Pediatric Patients. Experience in Two Institutions
Authors: Patricia Perez-Vera, Dafne Moreno Lorenzana, María Del Rocío Juárez-Velázquez, Daniel Alejandro Martínez-Anaya, Adriana Reyes-León, Adrián Hernández-Monterde, Maria Montserrat Aguilar, Oscar Soto Lerma, Martha Herrera-Almanza, Marta Zapata-Tarres, Luis Juarez-Villegas, Rocio Cardenas-Cardos, Roberto Rivera-Luna, Alberto Olaya-Vargas
Journal: Blood (2018)
Development and Preliminary Validation of the Lung Transplant Quality of Life (LT-QOL) Survey
Authors: Jonathan P. Singer, Allison Soong, Joan Chen, Pavan Shrestha, Hanjing Zhuo, Ying Gao, John R. Greenland, Steven R. Hays, Jasleen Kukreja, Jeffrey Golden, Steven E. Gregorich, Anita L. Stewart
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Although lung transplantation aims to improve health-related quality of life (HRQL), existing instruments fail to include health domains considered important in this population.Objectives: We aimed to develop a comprehensive lung transplant–specific instrument to address this shortcoming.Methods: We developed a pool of 126 candidate items addressing domains previously identified as important by lung transplant recipients. Through cognitive interviews conducted in 43 transplant recipients, items deemed irrelevant or redundant were dropped. The 84 remaining items were field tested in lung transplant recipients. Exploratory and confirmatory factor analyses were used to evaluate the factor structure, and scales were evaluated for internal consistency and construct validity.Measurements and Main Results: The 84-item preliminary survey was administered to 201 lung transplant recipients with a mean age of 57.9 (±12.7) years; 46% were female. After factor analyses and internal consistency evaluation, we retained 60 items comprising the Lung Transplant Quality of Life (LT-QOL) Survey. The LT-QOL contains 10 scales that measure symptoms, health perceptions, functioning, and well-being. The confirmatory factor analysis model had good approximate fit (comparative fit index = 0.990; standardized root-mean-square residual = 0.062). Cronbach αs for the 10 scales ranged from 0.75 to 0.95. Interscale correlations were consistent with hypothesized relationships. Subjects with severe chronic lung allograft dysfunction (n = 13) reported significantly worse HRQL than subjects without chronic lung allograft dysfunction (n = 168) on 6 of the 10 LT-QOL scales.Conclusions: The LT-QOL is a new, multidimensional instrument that characterizes and quantifies HRQL in lung transplant recipients.
Inhibition of BUB1 Kinase by BAY 1816032 Sensitizes Tumor Cells toward Taxanes, ATR, and PARP Inhibitors <i>In Vitro</i> and <i>In Vivo</i>
Authors: Gerhard Siemeister, Anne Mengel, Amaury E. Fernández-Montalván, Wilhelm Bone, Jens Schröder, Sabine Zitzmann-Kolbe, Hans Briem, Stefan Prechtl, Simon J. Holton, Ursula Mönning, Oliver von Ahsen, Sandra Johanssen, Arwed Cleve, Vera Pütter, Marion Hitchcock, Franz von Nussbaum, Michael Brands, Karl Ziegelbauer, Dominik Mumberg
Journal: Clinical Cancer Research (2018)

The catalytic function of BUB1 is required for chromosome arm resolution and positioning of the chromosomal passenger complex for resolution of spindle attachment errors and plays only a minor role in spindle assembly checkpoint activation. Here, we present the identification and preclinical pharmacologic profile of the first BUB1 kinase inhibitor with good bioavailability.The Bayer compound library was screened for BUB1 kinase inhibitors and medicinal chemistry efforts to improve target affinity and physicochemical and pharmacokinetic parameters resulting in the identification of BAY 1816032 were performed. BAY 1816032 was characterized for kinase selectivity, inhibition of BUB1 signaling, and inhibition of tumor cell proliferation alone and in combination with taxanes, ATR, and PARP inhibitors. Effects on tumor growth in vivo were evaluated using human triple-negative breast xenograft models.The highly selective compound BAY 1816032 showed long target residence time and induced chromosome mis-segregation upon combination with low concentrations of paclitaxel. It was synergistic or additive in combination with paclitaxel or docetaxel, as well as with ATR or PARP inhibitors in cellular assays. Tumor xenograft studies demonstrated a strong and statistically significant reduction of tumor size and excellent tolerability upon combination of BAY 1816032 with paclitaxel or olaparib as compared with the respective monotherapies.Our findings suggest clinical proof-of-concept studies evaluating BAY 1816032 in combination with taxanes or PARP inhibitors to enhance their efficacy and potentially overcome resistance.
Postpregnancy BMI in the Progression From Hypertensive Disorders of Pregnancy to Type 2 Diabetes
Authors: Simon Timpka, Jennifer J. Stuart, Lauren J. Tanz, Frank B. Hu, Paul W. Franks, Janet W. Rich-Edwards
Journal: Diabetes Care (2018)

OBJECTIVE To study the extent to which BMI after pregnancy adds to the elevated risk of postpregnancy type 2 diabetes in women with a history of hypertensive disorders of pregnancy (HDP) (preeclampsia or gestational hypertension). RESEARCH DESIGN AND METHODS We used data from the Nurses’ Health Study II, a prospective cohort study. In women aged 45–54 years without prior gestational diabetes mellitus, we investigated the interaction between BMI and HDP history on the risk of type 2 diabetes. For clinical and public health relevance, we focused on additive interaction. The main outcome measure was the relative excess risk due to interaction calculated from multivariable Cox proportional hazards models using normal weight as the reference group. RESULTS In total, 6,563 (11.7%) of 56,159 participants had a history of HDP and 1,341 women developed type 2 diabetes during 436,333 person-years. BMI was a strong risk factor for type 2 diabetes regardless of HDP history. However, there was evidence of an additive interaction between BMI and HDP for the risk of type 2 diabetes (P = 0.004). The attributable proportion of risk due to the interaction ranged from 0.12 (95% CI −0.22, 0.46) in women who were overweight to 0.36 (95% CI 0.13, 0.59) in women with obesity class I. CONCLUSIONS Maintaining a healthy weight may be of even greater importance in women with a history of HDP, compared with other women with a history of only normotensive pregnancies, to reduce midlife risk of type 2 diabetes.
Social Media Posts by Recreational Marijuana Companies and Administrative Code Regulations in Washington State
Authors: Megan A. Moreno, Aubrey D. Gower, Marina C. Jenkins, Josh Scheck, Jaymin Sohal, Bradley Kerr, Henry N. Young, Elizabeth Cox
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Recreational marijuana use was legalized in the state of Washington in 2012, and the Washington Administrative Code (WAC) 314-55-155 was implemented to limit the exposure of youths to marijuana advertisements. <h3>Objectives</h3> To evaluate the content of social media posts by marijuana companies and to assess the compliance of these posts with WAC regulations. <h3>Design, Setting, and Participants</h3> In a cross-sectional study, a content analysis of 1027 social media posts was conducted to identify and assess compliance of WAC regulations with the business pages of recreational marijuana companies located on Facebook and Twitter platforms in the state of Washington from December 1, 2015, through November 30, 2016. <h3>Main Outcomes and Measures</h3> Application of coding based on WAC regulations to focus on the prohibition of language that promoted the overconsumption of marijuana, that described its curative or therapeutic benefits, or that was designed to appeal to youths; and the requirements for warnings about intoxication, driving, health risks, and age restrictions for marijuana. <h3>Results</h3> Of the 1027 posts on Facebook and Twitter from business pages of 6 marijuana companies, Facebook followers ranged from 342 to 1592 persons and Twitter followers ranged from 374 to 2915 persons per company. Findings for WAC regulations included 17 posts (1.7%) that encouraged overconsumption; 137 posts (13.3%) that promoted therapeutic benefits; and 9 posts (0.01%) that appealed to youths. Requirements for warnings addressing intoxication, driving, health risks, and age restrictions were present on 110 posts (10.7%). Some businesses repeatedly violated particular regulations; 7 of 17 (41.2%) posts encouraging overconsumption derived from 1 marijuana company. <h3>Conclusions and Relevance</h3> Most social media posts by marijuana companies were consistent with WAC regulations that prohibit particular messages, but few companies provided required warning messages. Findings can be used toward implementation strategies for marijuana prevention to address these influential media messages.
The immune system profoundly restricts intratumor genetic heterogeneity
Authors: Idan Milo, Marie Bedora-Faure, Zacarias Garcia, Ronan Thibaut, Leïla Périé, Guy Shakhar, Ludovic Deriano, Philippe Bousso
Journal: Science Immunology (2018)

Tumors develop under the selective pressure of the immune system. However, it remains critical to establish how the immune system affects the clonal heterogeneity of tumors that often display cell-to-cell variation in genetic alterations and antigenic expression. To address these questions, we introduced a multicolor barcoding strategy to study the growth of a MYC-driven B cell lymphoma harboring a large degree of intratumor genetic diversity. Using intravital imaging, we visualized that lymphoma subclones grow as patches of sessile cells in the bone marrow, creating a spatially compartmentalized architecture for tumor diversity. Using multicolor barcoding and whole-exome sequencing, we demonstrated that immune responses strongly restrict intratumor genomic diversity and favor clonal dominance, a process mediated by the selective elimination of more immunogenic cells and amplified by epitope spreading. Anti-PD-1 treatment also narrowed intratumor diversity. Our results provide direct evidence that immune pressure shapes the level of intratumor genetic heterogeneity and have important implications for the design of therapeutic strategies.
Smartphone Photographs—Proceed, but With Caution
Authors: F. Thurston Drake
Journal: JAMA Surgery (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Measurable residual disease-guided treatment with azacitidine to prevent haematological relapse in patients with myelodysplastic syndrome and acute myeloid leukaemia (RELAZA2): an open-label, multicentre, phase 2 trial
Authors: Uwe Platzbecker, Jan Moritz Middeke, Katja Sockel, Regina Herbst, Dominik Wolf, Claudia D Baldus, Uta Oelschlägel, Anke Mütherig, Lars Fransecky, Richard Noppeney, Gesine Bug, Katharina S Götze, Alwin Krämer, Tilmann Bochtler, Matthias Stelljes, Christoph Groth, Antje Schubert, Marika Mende, Friedrich Stölzel, Christine Borkmann, Anne Sophie Kubasch, Malte von Bonin, Hubert Serve, Mathias Hänel, Ulrich Dührsen, Johannes Schetelig, Christoph Röllig, Michael Kramer, Gerhard Ehninger, Martin Bornhäuser, Christian Thiede
Journal: The Lancet Oncology (2018)
Radiomics and radiogenomics of primary liver cancers
Authors: Woo Kyoung Jeong, Neema Jamshidi, Ely Richard Felker, Steven Satish Raman, David Shinkuo Lu
Journal: Clinical and Molecular Hepatology (2018)

Concurrent advancements in imaging and genomic biomarkers have created opportunities to identify non-invasive imaging surrogates of molecular phenotypes. In order to develop such imaging surrogates radiomics and radiogenomics/imaging genomics will be necessary; there has been consistent progress in these fields for primary liver cancers. In this article we evaluate the current status of the field specifically with regards to hepatocellular carcinoma and intrahepatic cholangiocarcinoma, highlighting some of the up and coming results that were presented at the annual Radiological Society of North America Conference in 2017. There are an increasing number of studies in this area with a bias towards quantitative feature measurement, which is expected to benefit reproducibility of the findings and portends well for the future development of biomarkers for diagnosis, prognosis, and treatment response assessment. We review some of the advancements and look forward to some of the exciting future applications that are anticipated as the field develops.
Cardiovascular incidents in male professional football players with negative preparticipation cardiac screening results: an 8-year follow-up
Authors: Hilde Moseby Berge, Thor Einar Andersen, Roald Bahr
Journal: British Journal of Sports Medicine (2018)

Preparticipation cardiac screening of athletes aims to detect cardiovascular disease at an early stage to prevent sudden cardiac arrests and deaths. Few studies have described the cardiovascular outcomes in athletes classified as negative on screening.To identify cardiovascular incidents in a cohort of male professional football players who were cleared to play after a negative screening result.This is a retrospective 8-year follow-up study of 595 professional male football players in Norway who underwent preparticipation cardiac screening by experienced cardiologists, including electrocardiography (ECG) and echocardiography, in 2008. We performed a media search to identify sudden cardiovascular incidents between January 2008 and February 2016. Incidents were cross-checked with medical records.Six of the 595 players (1%), all classified as negative on cardiac screening, experienced severe cardiovascular incidents during follow-up. Retrospective review revealed abnormal ECG findings in one case, not recognised at the time of screening. Three players suffered a sudden cardiac arrest (all resuscitated successfully), one a myocardial infarction, one a transient ischaemic attack and one atrial flutter. Three of the players ignored chest pain, paresis, dyspnoea or near-syncope, two completed a match with symptoms before seeking medical assistance, one player's symptoms were misinterpreted and received inappropriate treatment initially, and two players were discharged from hospital without proper follow-up, despite having serious cardiovascular symptoms.A comprehensive preparticipation cardiac screening did not identify a subset of 6 of 595 players who experienced subsequent cardiovascular incidents as being at risk. It is important to remind athletes that a normal cardiac screening exam does not protect against all cardiac diseases. Timely reporting of symptoms is essential.
AB0104 Cartilage-like tissue generation by 3d-bioprinting of induced pluripotent stem cellsin a modified nanocellulose/alginate bioink
Authors: R. Castro-Viñuelas, A. Forsman, E. Karabulut, E. Romberg, C. Brantsing, M. Brittberg, A. Lindahl, P. Gatenholm, S. Simonsson
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Today, several hundreds of million people all over the world are suffering from different joint disorders; like osteoarthritis (OA). Further, traumatic cartilage lesions can develop into OA. Recent studies indicate that human-derived induced pluripotent stem cells (iPSCs) can be 3D bioprinted and directed to form cartilage-like tissue, thus offering new approaches to treat cartilage lessions.<sup>Nguyen <i>et al.</i> 2017</sup> The advantages of using an established iPSC line are unlimited cell source with regeneration capacity and chondrogenic differentiation potential. <h3>Objectives</h3> The aim of this study was to improve the generation of cartilage-like tissue when 3D bioprinting of iPSCs by using molecularly modified nanocelullose/alginate bioink to resemble natural environment found in the tissue. <h3>Methods</h3> In this study the chondrocyte-derived iPSC line "A2B" was used (Borestrom <i>et al.</i> 2014). These cells were bioprinted in combination with a modified nanocellulose and alginate bioink. Constructs obtained after the 3D bioprinting were cultured in chondrogenic medium in order to stimulate chondrogenic differentiation. Cell number and viability inside the prints was studied and histological analyses of the 3D printed constructs were performed. Furthermore, expression of pluripotency and chondrogenic specific genes was assessed by Taqman qPCR before and after differentiation. <h3>Results</h3> After 3D bioprinting high cell viability was found inside the constructs. 3D printed constructs were positively stained for alcian blue van gieson (AB-vG) staining, showing proteoglycans presence inside the prints (figure 1B). Molecular analyses showed high relative expression levels of the pluripotency-related gene Oct4 before starting the differentiation protocol. Cells inside the constructs express chondrogenic specific genes, such as collagen type 2 and Sox9 after 6 weeks of differentiation. Moreover, 3D printed constructs showed cartilage-resembles (figure 1A). <h3>Conclusions</h3> The 3D printing of the iPSc and the <i>in vitro</i> generation of cartilage-like tissue was successfully achieved using the modified nanocellulose/alginate bioink. This approach could be use in the future to model OA disease and to perform screenings of different therapeutic compounds. <h3>References</h3> [1] Nguyen D, et al. Cartilage Tissue Engineering by the 3D Bioprinting of iPS Cells in a Nanocellulose/Alginate Bioink. Sci Rep2017;7(1):658. [2] Borestrom C, et al. Footprint-free human induced pluripotent stem cells from articular cartilage with redifferentiation capacity: a first step toward a clinical-grade cell source. Stem Cells Transl Med2014;3;433–447. <h3>Disclosure of Interest</h3> None declared
Clinical experiences of cytotoxic chemotherapy in patients with lung cancer complicated by interstitial pneumonia who were treated with pirfenidone simultaneously: A retrospective observational study in single institution
Authors: Y. Yano, K. Nishida, M. Ishijima, T. Uenami, Y. Akazawa, T. Yamaguchi, M. Mori
Journal: Annals of Oncology (2018)
US doctors react to criticism from National Rifle Association
Authors: Owen Dyer
Journal: BMJ (2018)

Doctors across the United States reacted sharply when a tweet from the National Rifle Association suggested that they should “stay in their lane” rather than join the debate on gun control. The tweet, which came in response to a position paper from the American College of Physicians, was written just hours before a gunman killed 12 people at the Borderline Bar in Los Angeles.

The American College of Physicians’ paper was published in the Annals of Internal Medicine .1 The NRA first reacted with an editorial on its website, then with a tweet linking to that editorial. The tweet …
G3BP1 promotes DNA binding and activation of cGAS
Authors: Zhao-Shan Liu, Hong Cai, Wen Xue, Miao Wang, Tian Xia, Wan-Jin Li, Jia-Qing Xing, Ming Zhao, Yi-Jiao Huang, Shuai Chen, Sheng-Ming Wu, Xinzheng Wang, Xin Liu, Xue Pang, Zi-Yu Zhang, Tingting Li, Jiang Dai, Fangting Dong, Qing Xia, Ai-Ling Li, Tao Zhou, Zheng-gang Liu, Xue-Min Zhang, Tao Li
Journal: Nature Immunology (2018)