tbuckley/cabot-search huggingface dataset:
Melanoma models for the next generation of therapies
Authors: E. Elizabeth Patton, Kristen L. Mueller, David J. Adams, Niroshana Anandasabapathy, Andrew E. Aplin, Corine Bertolotto, Marcus Bosenberg, Craig J. Ceol, Christin E. Burd, Ping Chi, Meenhard Herlyn, Sheri L. Holmen, Florian A. Karreth, Charles K. Kaufman, Shaheen Khan, Sebastian Kobold, Eleonora Leucci, Carmit Levy, David B. Lombard, Amanda W. Lund, Kerrie L. Marie, Jean-Christophe Marine, Richard Marais, Martin McMahon, Carla Daniela Robles-Espinoza, Ze'ev A. Ronai, Yardena Samuels, Maria S. Soengas, Jessie Villanueva, Ashani T. Weeraratna, Richard M. White, Iwei Yeh, Jiyue Zhu, Leonard I. Zon, Marc S. Hurlbert, Glenn Merlino
Journal: Cancer Cell (2021)
Essential role of smooth muscle Rac1 in severe asthma-associated airway remodelling
Authors: Florian Dilasser, Lindsay Rose, Dorian Hassoun, Martin Klein, Morgane Rousselle, Carole Brosseau, Christophe Guignabert, Camille Taillé, Marie Christine Dombret, Leonarda Di Candia, Nicolas Heddebaut, Gregory Bouchaud, Marina Pretolani, Antoine Magnan, Gervaise Loirand, Vincent Sauzeau
Journal: Thorax (2021)

Background Severe asthma is a chronic lung disease characterised by inflammation, airway hyperresponsiveness (AHR) and airway remodelling. The molecular mechanisms underlying uncontrolled airway smooth muscle cell (aSMC) proliferation involved in pulmonary remodelling are still largely unknown. Small G proteins of the Rho family (RhoA, Rac1 and Cdc42) are key regulators of smooth muscle functions and we recently demonstrated that Rac1 is activated in aSMC from allergic mice. The objective of this study was to assess the role of Rac1 in severe asthma-associated airway remodelling. Methods and results Immunofluorescence analysis in human bronchial biopsies revealed an increased Rac1 activity in aSMC from patients with severe asthma compared with control subjects. Inhibition of Rac1 by EHT1864 showed that Rac1 signalling controlled human aSMC proliferation induced by mitogenic stimuli through the signal transducer and activator of transcription 3 (STAT3) signalling pathway. In vivo, specific deletion of Rac1 in SMC or pharmacological inhibition of Rac1 by nebulisation of NSC23766 prevented AHR and aSMC hyperplasia in a mouse model of severe asthma. Moreover, the Rac1 inhibitor prevented goblet cell hyperplasia and epithelial cell hypertrophy whereas treatment with corticosteroids had less effect. Nebulisation of NSC23766 also decreased eosinophil accumulation in the bronchoalveolar lavage of asthmatic mice. Conclusion This study demonstrates that Rac1 is overactive in the airways of patients with severe asthma and is essential for aSMC proliferation. It also provides evidence that Rac1 is causally involved in AHR and airway remodelling. Rac1 may represent as an interesting target for treating both AHR and airway remodelling of patients with severe asthma.
Annals Graphic Medicine - A Series of Unfortunate Events
Authors: Abey K. Thomas
Journal: Annals of Internal Medicine (2021)

Web ExclusivesFebruary 2021Annals Graphic Medicine - A Series of Unfortunate EventsFREEAbey K. Thomas, MDAbey K. Thomas, MDUT Southwestern Medical Center, Dallas, Texas (A.K.T.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G20-0009 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: UT Southwestern Medical Center, Dallas, Texas (A.K.T.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmjeConflictOfInterestForms.do?msNum=G20-0009.Author/Illustrator Information: Abey K. Thomas, MD, is an internal medicine hospitalist and a mentor to medical students at the University of Texas Southwestern Medical Center in Dallas, Texas (e-mail, abeyk.[email protected]edu; Twitter, @abeythomas).This article was published at Annals.org on 9 February 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics February 2021Volume 174, Issue 2Page: W22-W23 ePublished: 9 February 2021 Issue Published: February 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Screening for Carotid Artery Stenosis
Authors: Jill Jin
Journal: JAMA (2021)

US Preventive Services Task Force; Alex H. Krist, MD, MPH; Karina W. Davidson, PhD, MASc; Carol M. Mangione, MD, MSPH; Michael J. Barry, MD; Michael Cabana, MD, MA, MPH; Aaron B. Caughey, MD, PhD; Katrina Donahue, MD, MPH; Chyke A. Doubeni, MD, MPH; John W. Epling Jr, MD, MSEd; Martha Kubik, PhD, RN; Gbenga Ogedegbe, MD, MPH; Lori Pbert, PhD; Michael Silverstein, MD, MPH; Melissa A. Simon, MD, MPH; Chien-Wen Tseng, MD, MPH, MSEE; John B. Wong, MD
Autoimmune susceptibility gene <i>PTPN2</i> is required for clearance of adherent-invasive <i>Escherichia coli</i> by integrating bacterial uptake and lysosomal defence
Authors: Marianne Rebecca Spalinger, Ali Shawki, Pritha Chatterjee, Vinicius Canale, Alina Santos, Anica Sayoc-Becerra, Michael Scharl, Michel L Tremblay, James Borneman, Declan F McCole
Journal: Gut (2021)

Objectives Alterations in the intestinal microbiota are linked with a wide range of autoimmune and inflammatory conditions, including inflammatory bowel diseases (IBD), where pathobionts penetrate the intestinal barrier and promote inflammatory reactions. In patients with IBD, the ability of intestinal macrophages to efficiently clear invading pathogens is compromised resulting in increased bacterial translocation and excessive immune reactions. Here, we investigated how an IBD-associated loss-of-function variant in the protein tyrosine phosphatase non-receptor type 2 ( PTPN2 ) gene, or loss of PTPN2 expression affected the ability of macrophages to respond to invading bacteria. Design IBD patient-derived macrophages with wild-type (WT) PTPN2 or carrying the IBD-associated PTPN2 SNP, peritoneal macrophages from WT and constitutive PTPN2-knockout mice, as well as mice specifically lacking PTPN2 in macrophages were infected with non-invasive K12 Escherichia coli , the human adherent-invasive E. coli (AIEC) LF82 , or a novel mouse AIEC ( m AIEC) strain. Results Loss of PTPN2 severely compromises the ability of macrophages to clear invading bacteria. Specifically, loss of functional PTPN2 promoted pathobiont invasion/uptake into macrophages and intracellular survival/proliferation by three distinct mechanisms: Increased bacterial uptake was mediated by enhanced expression of carcinoembryonic antigen cellular adhesion molecule (CEACAM)1 and CEACAM6 in PTPN2 -deficient cells, while reduced bacterial clearance resulted from defects in autophagy coupled with compromised lysosomal acidification. In vivo, mice lacking PTPN2 in macrophages were more susceptible to m AIEC infection and m AIEC-induced disease. Conclusions Our findings reveal a tripartite regulatory mechanism by which PTPN2 preserves macrophage antibacterial function, thus crucially contributing to host defence against invading bacteria.
Decoding the Evolution of Melanin in Vertebrates
Authors: M.E. McNamara, V. Rossi, T.S. Slater, C.S. Rogers, A.-L. Ducrest, S. Dubey, A. Roulin
Journal: Trends in Ecology & Evolution (2021)

Melanins are widespread pigments in vertebrates, with important roles in visual signaling, UV protection, and homeostasis. Fossil evidence of melanin and melanin-bearing organelles - melanosomes - in ancient vertebrates may illuminate the evolution of melanin and its functions, but macroevolutionary trends are poorly resolved. Here, we integrate fossil data with current understanding of melanin function, biochemistry, and genetics. Mapping key genes onto phenotypic attributes of fossil vertebrates identifies potential genomic controls on melanin evolution. Taxonomic trends in the anatomical location, geometry, and chemistry of vertebrate melanosomes are linked to the evolution of endothermy. These shifts in melanin biology suggest fundamental links between melanization and vertebrate ecology. Tissue-specific and taxonomic trends in melanin chemistry support evidence for evolutionary tradeoffs between function and cytotoxicity.
選択的PCI術後の周術期心筋梗塞(PMI)の三次元血管内超音波後方散乱波解析の予測因子
Authors: Ohta Masaya, Ozaki Yukio, Hashimoto Yousuke, Ishikawa Masato, Okumura Masanori, Muramatsu Takashi, Naruse Hiroyuki, Ishii Jyunichi
Journal: Circulation (2015)
Abstract P156: Assessing the Effect of the Heart of New Ulm Project: a Population-Based Program to Reduce Cardiovascular Disease
Authors: Abbey C Sidebottom, Arthur Sillah, David M Vock, Michael M Miedema, Raquel Pereira, Gretchen Benson, Rebecca Lindberg, Jackie L Boucher, Thomas Knickelbine, Jeffrey J VanWormer
Journal: Circulation (2017)

Background: Despite a highly recognized priority for public health and healthcare to implement population-level strategies to reduce the burden of cardiovascular disease (CVD), limited evidence exists on the most effective strategies. Data collection and evaluation of large scale, community based-prevention programs can be challenging and costly to achieve. The Heart of New Ulm (HONU) Project, begun in 2009, is a population-based initiative with healthcare, community, and workplace interventions addressing multiple levels of the social-ecological model designed to reduce modifiable CVD risk factors in rural New Ulm, MN. The community is served by one health system, enabling the use of electronic health record (EHR) data for surveillance. Objective: To assess trends for CVD risk factors, events, and healthcare utilization for New Ulm residents compared to a matched control population. Methods: We matched New Ulm residents (n = 4,077) with controls (n = 4,077) from a regional community served by the same health system using refined covariate balance techniques to match on baseline demographics, CVD risk factors, and health care utilization. Mixed effects longitudinal models with adjustment for age and gender, and an interaction for time by community, were run. Model based estimates were constructed for the entire cohort at each time period. Results: Over the first 6 years of the HONU Project,blood pressure, LDL, total cholesterol, and triglycerides were managed better in New Ulm than the matched comparison community. The proportion of New Ulm residents with controlled blood pressure increased by 6.2 percentage points while the control group increased by 2 points. 10-year ASCVD risk scores showed less decline for New Ulm residents than controls (16 vs. 18.4). The intervention and control groups did not differ with regard to inpatient stays, CVD events, smoking, or glucose. Conclusions: Compared to a matched control population, we found improved control of CVD risk factors in the New Ulm Population exposed to the HONU Project.
Nursing Burnout and Patient Safety—Reply
Authors: Linda H. Aiken, Sean P. Clarke, Douglas M. Sloane, Julie Sochalski, Jeffrey H. Silber
Journal: JAMA (2003)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Vaccine advertising: preach to the converted or to the unaware?
Authors: Masha Krupenkin, Elad Yom-Tov, David Rothschild
Journal: npj Digital Medicine (2021)

Abstract Encouraging people to vaccinate is a challenging endeavor, but one which has tremendous public health benefits. Doing so requires overcoming barriers of awareness, availability, and (sometimes) vaccine hesitancy. Here we focus on nudging people to vaccinate through online advertising. We conducted a pre-registered online ads campaign encouraging people to vaccinate against three diseases: influenza, human papillomavirus, and herpes zoster. Ads were shown to ~69,000 people and were compared to similar ads shown to 8.6 million people. Outcome measures were clicks on ads and future searches for relevant terms. We find that ads have two main effects: First, a congruence effect whereby ads increase the likelihood of clicks and future searches by up to 116% in people who express an interest in the disease or the vaccine. Most commercial vaccine advertising is aimed entirely at this population. Second, we observed a priming effect, where ads shown to people who were searching for terms unrelated to the vaccine could be encouraged to click on them (odds ratios of 7.5–33.0) and, more often, search for the vaccine later (hazard ratios of 6.9–157.3). We provide analysis for optimizing vaccine advertising campaign budgets to balance the two populations. These findings demonstrate that digital advertising campaigns should consider not just advertising to direct keywords or to individuals that look exactly like existing customers, but consider tangential keywords that draw a wider target population who are likely earlier in their conversion funnel, thus increasing the number of people who vaccinate and maximizing vaccines uptake.
The effect of chemical structure of carboxylate molecules on hydroxyapatite nanoparticles. A structural and morphological study
Authors: Lorenzo Degli Esposti, Alessio Adamiano, Dritan Siliqi, Cinzia Giannini, Michele Iafisco
Journal: Bioactive Materials (2021)

Being the most abundant non-macromolecular organic component of bone, the role of citrate (Cit) in hydroxyapatite (HA) crystallization is of high relevance. In this work we have investigated the influence of hydroxycitrate (CitOH) and glutarate (Glr) on HA crystallization in terms of particle growth, composition, and morphology in comparison to Cit. CitOH and Glr have been selected for this work because they share the same backbone structure of Cit but bear different functional groups in the central region. Our data has revealed that CitOH strongly inhibits HA crystallization more efficiently than Cit. CitOH-HA nanoparticles are composed of platy, elongated particles similar to those of Cit-HA but they are ca. twice smaller and have a lower crystal order. On the other hand, Glr does not inhibit HA crystallization as Cit, but leads to the formation of OCP platelets that convert with maturation time to HA nanorods with larger aspect ratio than Cit-HA. In comparison to Cit-HA samples, Glr-HA nanoparticles have bigger dimensions, and higher structural order. Overall, our data reveal that the central carboxyl group of Cit is involved in the selective binding with HA crystal surface and in regulating HA crystal growth. The results of this work highlight new possibilities to control the formation of HA for designing advanced bioactive materials and give new insights on the role of the structure of Cit in regulating the HA morphology.
Relax, Keep Walking — A Practical Guide to Continuous Phylogeographic Inference with BEAST
Authors: Simon Dellicour, Mandev S Gill, Nuno R Faria, Andrew Rambaut, Oliver G Pybus, Marc A Suchard, Philippe Lemey
Journal: Molecular Biology and Evolution (2021)

Spatially explicit phylogeographic analyses can be performed with an inference framework that employs relaxed random walks to reconstruct phylogenetic dispersal histories in continuous space. This core model was first implemented 10 years ago and has opened up new opportunities in the field of phylodynamics, allowing researchers to map and analyze the spatial dissemination of rapidly evolving pathogens. We here provide a detailed and step-by-step guide on how to set up, run, and interpret continuous phylogeographic analyses using the programs BEAUti, BEAST, Tracer, and TreeAnnotator.
Epidemiology of Hypertension
Journal: BMJ (1952)

INTRODUCTION Blood pressure (BP) is a quantitative trait with a normal, continuous, bell-shaped (Gaussian) distribution pattern, skewed to the upper end in any general population (Figure 1.1), and hypertension represents a clinical definition of the upper part of the distribution curve. Figure 1.1 shows a distribution curve for diastolic BP plotted using BP measurements in 158,906 individuals aged 30-69 years screened for the Hypertension Detection and Follow-up Program in the United States (1).
Mutation of SPINOPHILIN (PPP1R9B) found in human tumors promotes the tumorigenic and stemness properties of cells
Authors: Eva M Verdugo-Sivianes, Ana M Rojas, Sandra Muñoz-Galván, Daniel Otero-Albiol, Amancio Carnero
Journal: Theranostics (2021)

Rationale: SPINOPHILIN (SPN, PPP1R9B) is an important tumor suppressor involved in the progression and malignancy of different tumors depending on its association with protein phosphatase 1 (PP1) and the ability of the PP1-SPN holoenzyme to dephosphorylate retinoblastoma (pRB).Methods: We performed a mutational analysis of SPN in human tumors, focusing on the region of interaction with PP1 and pRB.We explored the effect of the SPN-A566V mutation in an immortalized non-tumorigenic cell line of epithelial breast tissue, MCF10A, and in two different p53-mutated breast cancer cells lines, T47D and MDA-MB-468.Results: We characterized an oncogenic mutation of SPN found in human tumor samples, SPN-A566V, that affects both the SPN-PP1 interaction and its phosphatase activity.The SPN-A566V mutation does not affect the interaction of the PP1-SPN holoenzyme with pocket proteins pRB, p107 and p130, but it affects its ability to dephosphorylate them during G0/G1 and G1, indicating that the PP1-SPN holoenzyme regulates cell cycle progression.SPN-A566V also promoted stemness, establishing a connection between the cell cycle and stem cell biology via pocket proteins and PP1-SPN regulation.However, only cells with both SPN-A566V and mutant p53 have increased tumorigenic and stemness properties.Conclusions: SPN-A566V, or other equivalent mutations, could be late events that promote tumor progression by increasing the CSC pool and, eventually, the malignant behavior of the tumor.
Transcriptomic Analysis of Laser Capture Microdissected Tumors Reveals Cancer- and Stromal-Specific Molecular Subtypes of Pancreatic Ductal Adenocarcinoma
Authors: David J. Birnbaum, Sebastian K.S. Begg, Pascal Finetti, Charles Vanderburg, Anupriya S. Kulkarni, Azfar Neyaz, Thomas Hank, Eric Tai, Vikram Deshpande, François Bertucci, Daniel Birnbaum, Keith D. Lillemoe, Andrew L. Warshaw, Mari Mino-Kenudson, Carlos Fernandez-Del Castillo, David T. Ting, Andrew S. Liss
Journal: Clinical Cancer Research (2021)

Pancreatic ductal adenocarcinoma (PDAC) lethality is multifactorial; although studies have identified transcriptional and genetic subsets of tumors with different prognostic significance, there is limited understanding of features associated with the minority of patients who have durable remission after surgical resection. In this study, we performed laser capture microdissection (LCM) of PDAC samples to define their cancer- and stroma-specific molecular subtypes and identify a prognostic gene expression signature for short-term and long-term survival. LCM and RNA sequencing (RNA-seq) analysis of cancer and adjacent stroma of 19 treatment-naïve PDAC tumors was performed. Gene expression signatures were tested for their robustness in a large independent validation set. An RNA-ISH assay with pooled probes for genes associated with disease-free survival (DFS) was developed to probe 111 PDAC tumor samples. Gene expression profiling identified four subtypes of cancer cells (C1-C4) and three subtypes of cancer-adjacent stroma (S1-S3). These stroma-specific subtypes were associated with DFS (P = 5.55E-07), with S1 associated with better prognoses when paired with C1 and C2. Thirteen genes were found to be predominantly expressed in cancer cells and corresponded with DFS in a validation using existing RNA-seq datasets. A second validation on an independent cohort of patients using RNA-ISH probes to six of these prognostic genes demonstrated significant association with overall survival (median 17 vs. 25 months; P < 0.02). Our results identified specific signatures from the epithelial and the stroma components of PDAC, which add clarity to the nature of PDAC molecular subtypes and may help predict survival.
Abstract 13654: Effects of Therapeutic Lowering of Non-High Density Lipoprotein Cholesterol on Cardiovascular Outcomes Among Women versus Men: A Meta- Regression Analysis
Authors: Safi U Khan, Adeel Arshad, Muhammad Z Khan, Mohammad S Khan, Victor Okunrintemi, Eve-Marie Benson, Roger S Blumenthal, Erin D Michos
Journal: Circulation (2019)

Introduction: Non-high density lipoprotein cholesterol (non-HDL-C) and triglyceride levels are stronger risk factors for atherosclerotic cardiovascular disease (ASCVD) in women than in men. However...