tbuckley/cabot-search huggingface dataset:
Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis
Authors: Laura B Nellums, Hayley Thompson, Alison Holmes, Enrique Castro-Sánchez, Jonathan A Otter, Marie Norredam, Jon S Friedland, Sally Hargreaves
Journal: The Lancet Infectious Diseases (2018)

Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings.
Abstract PR01: Modeling colorectal cancer in vivo through CRISPR-based genome editing
Authors: Teng Han, Emma M. Schatoff, Charles Murphy, Maria Paz Zafra, John Wilkinson, Olivier Elemento, Lukas E. Dow
Journal: Cancer Research (2018)

Abstract In addition to activating and inactivating mutations in protein coding genes, cancer cells commonly show gross structural abnormalities in their genomes. These include deletions, duplications, inversions, and translocations. Unfortunately, conventional gene targeting- and RNAi-based approaches are not easily applied to study chromosome rearrangements. To enable this, we developed flexible CRISPR-based in vivo models systems that drive the generation of targeted genomic breaks, and the induction of gross chromosomal aberrations, without the need for viral delivery of CRISPR components. Using this approach we have produced novel transgenic systems to recapitulate two recurrent genomic rearrangements observed in human colorectal cancer and provide the first evidence that these events are sufficient to initiate tumor development. Further, we show that these tumors, while histologically similar to Apc mutant CRC, are molecularly distinct and are exquisitely sensitive to therapies targeting the Wnt pathway. We are now using this and other genome-editing platforms to systematically investigate the role of other recurrent genetic alterations in GI malignancies. Citation Format: Teng Han, Emma M. Schatoff, Charles Murphy, Maria Paz Zafra, John Wilkinson, Olivier Elemento, Lukas E. Dow. Modeling colorectal cancer in vivo through CRISPR-based genome editing [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr PR01.
Abstract 3564: A Multi-Stage Evaluation of Genetic Association with Early-Onset Coronary Artery Disease in <i>MYLK</i> Gene
Authors: Liyong Wang, Elizabeth R Hauser, David Crosslin, Sarah Nelson, A B Hale, Simon Gregory, Svati H Shah, William E Kraus, Pascal J Goldschmidt-Clermont, Jeffery M Vance
Journal: Circulation (2007)

Background: Consistent linkage evidence has been found for coronary artery disease (CAD) at chromosome 3q13–21. To fine map the region, we previously conducted a peak-wide association survey using single nucleotide polymorphisms (SNPs) evenly spaced at 100 kb intervals. While strongest association was found at Kalirin gene, multiple genes displayed evidence for association with early-onset CAD, including the myosin light chain kinase (MYLK) gene. MYLK is a member of the Kalirin-RhoGTPase pathway that we have proposed previously to be important in CAD. Methods: To thoroughly evaluate the association at MYLK , we examined 46 tagging and functional SNPs across the gene in a case-control dataset with early-onset CAD (N=750), resulting in an average density of one SNP every 6 kb. Significant results were then validated in families with early-onset CAD (N=2954). As a third evaluation, the probands (N=560) of the families were compared to the controls (N=291) from the case-control dataset. Finally, validated SNPs were examined for correlation with atherosclerosis in 145 aorta specimens. Results: Multiple SNPs were significant in the initial screening in the case-control dataset (p=0.001 to 0.038). However, only three of them were validated in all datasets (p=0.001 to 0.046). In addition, the risk alleles of the three SNPs were correlated with higher atherosclerosis burden in aortas (p=0.007 to 0.040). The three SNPs are in linkage disequilibrium with each other (r 2&gt; 0.9) and span over 50 kb region near the 5’ end of the gene. Conclusions: Our multi-stage evaluation strongly supports MYLK as a novel CAD susceptibility gene. MYLK regulates smooth muscle cell contraction and endothelial cell permeability through catalyzing the phorsphorylation of the regulatory myosin light chain. The known functions of MYLK provide a plausible mechanism for its involvement in the development of atherosclerosis.
Pay It Forward: Building Capacity to Treat Hepatitis C by Training Our Own Residents
Authors: Thomas Couri, Tanmayi Gupta, George Weyer, Andrew Aronsohn
Journal: Hepatology (2018)

1Department of Internal MedicineUniversity of ChicagoChicagoIllinois 2Partners HealthcareSomervilleMassachusetts 3Department of Internal Medicine Section of Gastroenterology, Hepatology, and NutritionUniversity of ChicagoChicagoIllinois *ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO: Thomas Couri, M.D. Department of Internal Medicine University of Chicago 5841 S. Maryland Avenue Chicago, IL 60637 E‐mail: [email protected] Tel.: +1‐773‐702‐6840 Fax: +1‐773‐702‐2230
The New Hypertension Guidelines
Authors: Clyde W. Yancy, Gregg C. Fonarow
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Re-evaluating microglia expression profiles using RiboTag and cell isolation strategies
Authors: Zhana Haimon, Alon Volaski, Johannes Orthgiess, Sigalit Boura-Halfon, Diana Varol, Anat Shemer, Simon Yona, Binyamin Zuckerman, Eyal David, Louise Chappell-Maor, Ingo Bechmann, Martin Gericke, Igor Ulitsky, Steffen Jung
Journal: Nature Immunology (2018)
Scabies outbreaks in ten care homes for elderly people: a prospective study of clinical features, epidemiology, and treatment outcomes
Authors: Jackie A Cassell, Jo Middleton, Ananth Nalabanda, Stefania Lanza, Michael G Head, Jennifer Bostock, Kirsty Hewitt, Christopher Iain Jones, Charles Darley, Simran Karir, Stephen L Walker
Journal: The Lancet Infectious Diseases (2018)

Scabies outbreaks in residential and nursing care homes for elderly people are common, subject to diagnostic delay, and hard to control. We studied clinical features, epidemiology, and outcomes of outbreaks in the UK between 2014 and 2015.We did a prospective observational study in residential care homes for elderly people in southeast England that reported scabies outbreaks to Public Health England health protection teams. An outbreak was defined as two or more cases of scabies (in either residents or staff) at a single care home. All patients who provided informed consent were included; patients with dementia were included if a personal or nominated consultee (ie, a family member or nominated staff member) endorsed participation. Dermatology-trained physicians examined residents at initial clinical visits, which were followed by two mass treatments with topical scabicide as per local health protection team guidance. Follow-up clinical visits were held 6 weeks after initial visits. Scabies was diagnosed through pre-defined case definitions as definite, probable, or possible with dermatoscopy and microscopy as appropriate.230 residents were examined in ten outbreaks between Jan 23, 2014, and April 13, 2015. Median age was 86·9 years (IQR 81·5-92·3), 174 (76%) were female, and 157 (68%) had dementia. 61 (27%) residents were diagnosed with definite, probable, or possible scabies, of whom three had crusted scabies. Physical signs differed substantially from classic presentations. 31 (51%) of the 61 people diagnosed with scabies were asymptomatic, and only 25 (41%) had burrows. Mites were visualised with dermatoscopy in seven (11%) patients, and further confirmed by microscopy in three (5%). 35 (57%) cases had signs of scabies only on areas of the body that would normally be covered. Dementia was the only risk factor for a scabies diagnosis that we identified (odds ratio 2·37 [95% CI 1·38-4·07]). At clinical follow-up, 50 people who were initially diagnosed with scabies were examined. No new cases of scabies were detected, but infestation persisted in ten people.Clinical presentation of scabies in elderly residents of care homes differs from classic descriptions familiar to clinicians. This difference probably contributes to delayed recognition and suboptimal management in this vulnerable group. Dermatoscopy and microscopy were of little value. Health-care workers should be aware of the different presentation of scabies in elderly people, and should do thorough examinations, particularly in people with dementia.Public Health England and British Skin Foundation.
Role of Elevated <i>PHIP</i> Copy Number as a Prognostic and Progression Marker for Cutaneous Melanoma
Authors: Vladimir Bezrookove, Mehdi Nosrati, James R. Miller, David De Semir, Altaf A. Dar, Elham Vosoughi, Edith Vaquero, Antje Sucker, Alexander J. Lazar, Jeffrey E. Gershenwald, Michael A. Davies, Dirk Schadendorf, Mohammed Kashani-Sabet
Journal: Clinical Cancer Research (2018)

Purpose: Previous studies have indicated an important role for pleckstrin homology domain-interacting protein (PHIP) as a marker and mediator of melanoma metastasis. Here we aimed to confirm the role of PHIP copy number in successive stages of melanoma progression.Experimental Design:PHIP copy number was examined using FISH in three independent cohorts by recording the percentage of cells harboring ≥3 copies of PHIP The impact of PHIP copy number on survival was assessed using Cox regression analysis. The enrichment of PHIP was assessed in various molecular melanoma subtypes. PHIP expression was analyzed in The Cancer Genome Atlas (TCGA) melanoma cohort.Results: Elevated PHIP copy number was significantly predictive of reduced distant metastasis-free survival (DMFS) and disease-specific survival (DSS), and increased prevalence of ulceration in primary melanoma (cohort No. 1). By multivariate analysis, PHIP FISH scores were independently predictive of DMFS and DSS. PHIP copy number was enriched in metastatic melanomas harboring mutant NRAS or expressing PTEN protein (cohort No. 2). PHIP copy number was significantly elevated in metastatic melanomas when compared with matched primary tumors from the same patient (cohort No. 3). Several of these associations were replicated using TCGA cohort analysis.Conclusions: These results underscore the important role of PHIP copy-number elevation in melanoma progression, and identify molecular subtypes of melanoma in which PHIP is enriched. Finally, as elevated PHIP copy number appears to be selected for during the progression of primary to metastatic melanoma, these results confirm PHIP as a promising therapeutic target for melanoma. Clin Cancer Res; 24(17); 4119-25. ©2018 AACR.
Development of Inhalable Superparamagnetic Iron Oxide Nanoparticles (SPIONs) in Microparticulate System for Antituberculosis Drug Delivery
Authors: Margarida S. Miranda, Márcia T. Rodrigues, Rui M. A. Domingues, Rui R. Costa, Elvira Paz, Carlos Rodríguez‐Abreu, Paulo Freitas, Bernardo G. Almeida, Maria Alice Carvalho, Carine Gonçalves, Catarina M. Ferreira, Egídio Torrado, Rui L. Reis, Jorge Pedrosa, Manuela E. Gomes
Journal: Advanced Healthcare Materials (2018)

Abstract Tuberculosis (TB) is an infectious disease which affects millions of people worldwide. Inhalable polymeric dry powders are promising alternatives as anti‐TB drug carriers to the alveoli milieu and infected macrophages, with potential to significantly improve the therapeutics efficiency. Here, the development of a magnetically responsive microparticulate system for pulmonary delivery of an anti‐TB drug candidate (P3) is reported. Microparticles (MPs) are developed based on a cast method using calcium carbonate sacrificial templates and incorporate superparamagnetic iron oxide nanoparticles to concentrate MPs in alveoli and enable drug on demand release upon actuation of an external alternate magnetic field (AMF). The MPs are shown to be suitable for P3 delivery to the lower airways and for alveolar macrophage phagocytosis. The developed MPs reveal unique and promising features to be used as an inhalable dry powder allowing the AMF control over dosage and frequency of drug delivery anticipating improved TB treatments.
Macrophages contribute to the pathogenesis of sclerosing cholangitis in mice
Authors: Maria Eugenia Guicciardi, Christy E. Trussoni, Anuradha Krishnan, Steven F. Bronk, Maria J. Lorenzo Pisarello, Steven P. O'Hara, Patrick L. Splinter, Yandong Gao, Pamela Vig, Alexander Revzin, Nicholas F. LaRusso, Gregory J. Gores
Journal: Journal of Hepatology (2018)
Playing the Melanoma Endgame
Authors: Jessica L.F. Teh, Andrew E. Aplin
Journal: Clinical Cancer Research (2018)

Treatments for melanoma are of two main types: targeted therapies and immune checkpoint inhibitors. However, both are effective in only a subset of patients and are limited by acquired resistance. Here, the authors present the preclinical basis to broadly target different forms of therapy-resistant melanoma. Clin Cancer Res; 24(19); 4629-30. ©2018 AACRSee related article by Zhang et al., p. 4771.
Effects of Perinatal Exposure to Dibutyltin Chloride on Fat and Glucose Metabolism in Mice, and Molecular Mechanisms, <i>in Vitro</i>
Authors: Raquel Chamorro-García, Bassem M. Shoucri, Sigal Willner, Heidi Käch, Amanda Janesick, Bruce Blumberg
Journal: Environmental Health Perspectives (2018)

Background: The organotin dibutyltin (DBT) is used in the manufacture of polyvinyl chloride (PVC) plastics, in construction materials, and in medical devices. Previous animal studies showed detrimental effects of DBT during in utero development at relatively high doses, but little was known about the effects of DBT exposure at environmentally relevant doses on endpoints such as obesity and metabolic disease. Objectives: We tested the potential obesogenic effects of DBT using in vitro and in vivo models. Methods. We evaluated the effects of DBT on nuclear receptor activation and adipogenic potential using human and mouse multipotent mesenchymal stromal stem cells (MSCs). We also evaluated the effects of perinatal exposure to environmentally relevant doses of DBT in C57BL/6J mice. Results: DBT activated human and mouse PPARγ and RXRα in transient transfection assays, increased expression of adipogenic genes, promoted adipogenic differentiation and increased lipid accumulation in mouse and human MSCs, in vitro. DBT-induced adipogenic differentiation was abolished by the PPARγ antagonist T0070907, indicating that DBT was acting primarily through PPARγ. Perinatal exposure to low doses of DBT led to increased fat storage, decreased glucose tolerance, and increased circulating leptin levels in male, but not female, mice. Conclusions: DBT acted as an obesogen by inducing lipid accumulation in human and mouse MSCs through a PPARγ-dependent pathway. In vivo exposure to biologically relevant doses of DBT during perinatal development led to increased fat storage, elevated leptin levels in plasma, and glucose intolerance in mice. Based on these findings, we posit that monitoring of DBT levels in human samples may aid in understanding and potentially preventing the rising rates of metabolic disorders in human populations. https://doi.org/10.1289/EHP3030
Adjuvant Vascular Endothelial Growth Factor–targeted Therapy in Renal Cell Carcinoma: A Systematic Review and Pooled Analysis
Authors: Maxine Sun, Lorenzo Marconi, Tim Eisen, Bernard Escudier, Rachel H. Giles, Naomi B. Haas, Lauren C. Harshman, David I. Quinn, James Larkin, Sumanta K. Pal, Thomas Powles, Christopher W. Ryan, Cora N. Sternberg, Robert Uzzo, Toni K. Choueiri, Axel Bex
Journal: European Urology (2018)
Persistence of treatment with biologics for patients with psoriasis: a real‐world analysis of 16 545 biologic‐naïve patients from the French National Health Insurance database (SNIIRAM)
Authors: E. Sbidian, M. Mezzarobba, A. Weill, J. Coste, J. Rudant
Journal: British Journal of Dermatology (2018)

Long-term clinical effectiveness of biologics in psoriasis is needed.We aimed to assess the long-term persistence of biologics used to treat psoriasis in a real-life setting.All adults with psoriasis having been registered in the French National Health Insurance database (SNIIRAM) between 2008 and 2016 were eligible for inclusion. Psoriasis was defined as the fulfilment of at least two prescriptions for topical formulations of a vitamin D derivative within a 2-year period. The study population comprised biologic-naïve patients, i.e. those with a first prescription of etanercept, infliximab, adalimumab or ustekinumab. Persistence of treatment with a biologic was defined as the time interval between initiation and discontinuation.In this nationwide population-based cohort, 16 545 out of 874 549 patients with psoriasis were biologic-naïve (mean age 48·6 years; males 57·3%, mean follow-up 3·6 years). The mean ± SD length of follow-up for biologic-naïve patients was 3·6 ± 2·4 years. There were 9988 treatment discontinuations. Kaplan-Meier survival analyses revealed a persistence rate of 61·9% for the first, 33·3% for the third and 22·6% for the fifth year. Ustekinumab had a higher persistence rate than the other biologics. This finding should be interpreted with caution, in view of differences in administration between the biologics. About 85% of patients, having discontinued their first biologic, resumed systemic treatment of some type in the following year (biologics in 85% of cases).Our data suggest that biologics are less effective than physicians have been led to believe in a real-life, nonselected population. Further, long-term disease control requires several courses of different biologics.
Automated typing of red blood cell and platelet antigens: a whole-genome sequencing study
Authors: William J Lane, Connie M Westhoff, Nicholas S Gleadall, Maria Aguad, Robin Smeland-Wagman, Sunitha Vege, Daimon P Simmons, Helen H Mah, Matthew S Lebo, Klaudia Walter, Nicole Soranzo, Emanuele Di Angelantonio, John Danesh, David J Roberts, Nick A Watkins, Willem H Ouwehand, Adam S Butterworth, Richard M Kaufman, Heidi L Rehm, Leslie E Silberstein, Robert C Green, David W. Bates, Carrie Blout, Kurt D. Christensen, Allison L. Cirino, Carolyn Y. Ho, Joel B. Krier, Lisa S. Lehmann, Calum A. MacRae, Cynthia C. Morton, Denise L. Perry, Christine E. Seidman, Shamil R. Sunyaev, Jason L. Vassy, Erica Schonman, Tiffany Nguyen, Eleanor Steffens, Wendi Nicole Betting, Samuel J. Aronson, Ozge Ceyhan-Birsoy, Kalotina Machini, Heather M. McLaughlin, Danielle R. Azzariti, Ellen A. Tsai, Jennifer Blumenthal-Barby, Lindsay Z. Feuerman, Amy L. McGuire, Kaitlyn Lee, Jill O. Robinson, Melody J. Slashinski, Pamela M. Diamond, Kelly Davis, Peter A. Ubel, Peter Kraft, J. Scott Roberts, Judy E. Garber, Tina Hambuch, Michael F. Murray, Isaac Kohane, Sek Won Kong
Journal: The Lancet Haematology (2018)
Exploratory Analysis of Brigatinib Activity in Patients With Anaplastic Lymphoma Kinase-Positive Non–Small-Cell Lung Cancer and Brain Metastases in Two Clinical Trials
Authors: D. Ross Camidge, Dong-Wan Kim, Marcello Tiseo, Corey J. Langer, Myung-Ju Ahn, Alice T. Shaw, Rudolf M. Huber, Maximilian J. Hochmair, Dae Ho Lee, Lyudmila A. Bazhenova, Kathryn A. Gold, Sai-Hong Ignatius Ou, Howard L. West, William Reichmann, Jeff Haney, Tim Clackson, David Kerstein, Scott N. Gettinger
Journal: Journal of Clinical Oncology (2018)

Purpose In patients with crizotinib-treated, anaplastic lymphoma kinase gene ( ALK)-rearranged non–small-cell lung cancer (ALK-positive NSCLC), initial disease progression often occurs in the CNS. We evaluated brigatinib, a next-generation ALK inhibitor, in patients with ALK-positive NSCLC with brain metastases. Patients and Methods Patients with ALK-positive NSCLC received brigatinib (90 to 240 mg total daily) in a phase I/II trial (phI/II; ClinicalTrials.gov identifier: NCT01449461) and in the subsequent randomized phase II trial ALTA (ALK in Lung Cancer Trial of AP26113; ClinicalTrials.gov identifier: NCT02094573; patients in arm A received 90 mg once daily; patients in arm B received 180 mg once daily with 7-day lead-in at 90 mg). Primary end points (systemic objective response rates [ORRs]) were previously reported. Independent review committees assessed intracranial efficacy in patients with baseline brain metastases. Results Most patients with ALK-positive NSCLC had baseline brain metastases (50 of 79 [63%], phI/II; 80 of 112 [71%] and 73 of 110 [66%] in ALTA arms A and B, respectively), many of whom had no prior brain radiotherapy (23 of 50 [46%], phI/II; 32 of 80 [40%], ALTA arm A; 30 of 73 [41%], arm B). All patients, except four in phI/II, had received crizotinib. Among patients with measurable (≥ 10 mm) brain metastases, confirmed intracranial ORR was 53% (eight of 15; 95% CI, 27% to 79%) in phI/II, 46% (12 of 26; 95% CI, 27% to 67%) in ALTA arm A, and 67% (12 of 18; 95% CI, 41% to 87%) in arm B. Intracranial ORRs were similar in subsets without prior radiation or progression postradiation. Among patients with any baseline brain metastases, median intracranial progression-free survival (iPFS) was 14.6 months (95% CI, 12.7 to 36.8 months), phI/II; 15.6 months (95% CI, 9.0 to 18.3 months), ALTA arm A; 18.4 months (95% CI, 12.8 months to not reached), ALTA arm B. Conclusion Brigatinib yielded substantial intracranial responses and durable iPFS in ALK-positive, crizotinib-treated NSCLC, with highest iPFS in patients receiving 180 mg once daily (with lead-in).
Intrinsic apoptosis circumvents the functional decline of circulating platelets but does not cause the storage lesion
Authors: Irina Pleines, Marion Lebois, Pradnya Gangatirkar, Amanda E. Au, Rachael M. Lane, Katya J. Henley, Maria Kauppi, Jason Corbin, Ping Cannon, Jonathan Bernardini, Imala Alwis, Kate E. Jarman, Sarah Ellis, Donald Metcalf, Shaun P. Jackson, Simone M. Schoenwaelder, Benjamin T. Kile, Emma C. Josefsson
Journal: Blood (2018)