tbuckley/cabot-search huggingface dataset:
Changes in macrophage transcriptome associate with systemic sclerosis and mediate <i>GSDMA</i> contribution to disease risk
Authors: Aida Moreno-Moral, Marta Bagnati, Surya Koturan, Jeong-Hun Ko, Carmen Fonseca, Nathan Harmston, Laurence Game, Javier Martin, Voon Ong, David J Abraham, Christopher P Denton, Jacques Behmoaras, Enrico Petretto
Journal: Annals of the Rheumatic Diseases (2018)

Several common and rare risk variants have been reported for systemic sclerosis (SSc), but the effector cell(s) mediating the function of these genetic variants remains to be elucidated. While innate immune cells have been proposed as the critical targets to interfere with the disease process underlying SSc, no studies have comprehensively established their effector role. Here we investigated the contribution of monocyte-derived macrophages (MDMs) in mediating genetic susceptibility to SSc.We carried out RNA sequencing and genome-wide genotyping in MDMs from 57 patients with SSc and 15 controls. Our differential expression and expression quantitative trait locus (eQTL) analysis in SSc was further integrated with epigenetic, expression and eQTL data from skin, monocytes, neutrophils and lymphocytes.We identified 602 genes upregulated and downregulated in SSc macrophages that were significantly enriched for genes previously implicated in SSc susceptibility (P=5×10-4), and 270 cis-regulated genes in MDMs. Among these, GSDMA was reported to carry an SSc risk variant (rs3894194) regulating expression of neighbouring genes in blood. We show that GSDMA is upregulated in SSc MDMs (P=8.4×10-4) but not in the skin, and is a significant eQTL in SSc macrophages and lipopolysaccharide/interferon gamma (IFNγ)-stimulated monocytes. Furthermore, we identify an SSc macrophage transcriptome signature characterised by upregulation of glycolysis, hypoxia and mTOR signalling and a downregulation of IFNγ response pathways.Our data further establish the link between macrophages and SSc, and suggest that the contribution of the rs3894194 risk variant to SSc susceptibility can be mediated by GSDMA expression in macrophages.
Microspheres as intraocular therapeutic tools in chronic diseases of the optic nerve and retina
Authors: Irene Bravo-Osuna, Vanessa Andrés-Guerrero, Alicia Arranz-Romera, Sergio Esteban-Pérez, Irene T. Molina-Martínez, Rocío Herrero-Vanrell
Journal: Advanced Drug Delivery Reviews (2018)
Epidemiological Data from the Algerian Multiple Myeloma Registry (AMMR) over 2 Years (June 2014-June 2016): Report of the Algerian Multiple Myeloma Study Group (GETMA)
Authors: M Saidi, MT Abad, S Taoussi, C Ghezlane, RM Hamladji, R Ahmed Nacer, F Belhadri, H Moussaoui, H Ait Ali, H Aftisse, Fz Ardjoun, SE Belakehal, C Rahali, M Belhani, N Boudjerra, Y Berkouk, M Ramaoun, H Ahmidatou, MA Bekadja, S Talhi, H Ouldjeriouat, F Grifi, S Boughrira, K Smaili, N Mesli, F Bendahmane, S Hamdi, Fz Belkhodja, A Amoura, H Menia, H Rechache, Z Zouaoui, A El mestari, H Touhami, R Mrabet, N Lakhdari, Z Brahimi, S Zeghouati, N Sidi Mansour, M Benhalilou, N Mehalhal, B Bendjabellah, W Chehili, A Bachiri, S Abderahmani, Y Ouarhlent, H Zidani, S Nekkal, Y Bouchakor, H Hamouda, F Mehdid, D Saidi, F Baichi, M Benakli
Journal: Blood (2017)
Population Genomic Analysis Reveals Contrasting Demographic Changes of Two Closely Related Dolphin Species in the Last Glacial
Authors: Nagarjun Vijay, Chungoo Park, Jooseong Oh, Soyeong Jin, Elizabeth Kern, Hyun Woo Kim, Jianzhi Zhang, Joong-Ki Park
Journal: Molecular Biology and Evolution (2018)

Population genomic data can be used to infer historical effective population sizes (Ne), which help study the impact of past climate changes on biodiversity. Previous genome sequencing of one individual of the common bottlenose dolphin Tursiops truncatus revealed an unusual, sharp rise in Ne during the last glacial, raising questions about the reliability, generality, underlying cause, and biological implication of this finding. Here we first verify this result by additional sampling of T. truncatus. We then sequence and analyze the genomes of its close relative, the Indo-Pacific bottlenose dolphin T. aduncus. The two species exhibit contrasting demographic changes in the last glacial, likely through actual changes in population size and/or alterations in the level of gene flow among populations. Our findings suggest that even closely related species can have drastically different responses to climatic changes, making predicting the fate of individual species in the ongoing global warming a serious challenge.
Communicating With Pediatric Families at End-of-Life Is Not a Fantasy
Authors: Connie M. Ulrich, Kim Mooney-Doyle, Christine Grady
Journal: The American Journal of Bioethics (2018)

The serious illness of a child is a stressful event for any parent. Further, a child's admission to a children's hospital, dedicated to pediatric care and research, can engender a host of parental ...
The D816V-KIT Mutation Causes IL-6 Upregulation In Human Mast Cells
Authors: Araceli Tobío, Pahul Hanjra, Geethani Bandara, Hirsh D. Komarow, Melody C. Carter, Daly Cantave, Dean D. Metcalfe, Ana Olivera
Journal: Journal of Allergy and Clinical Immunology (2018)
Consensus document on dog and cat allergy
Authors: I. Dávila, J. Domínguez‐Ortega, A. Navarro‐Pulido, A. Alonso, D. Antolín‐Amerigo, E. González‐Mancebo, C. Martín‐García, B. Núñez‐Acevedo, N. Prior, M. Reche, A. Rosado, J. Ruiz‐Hornillos, M. C. Sánchez, M. Torrecillas
Journal: Allergy (2018)

Abstract The prevalence of sensitization to dogs and cats varies by country, exposure time and predisposition to atopy. It is estimated that 26% of European adults coming to the clinic for suspected allergy to inhalant allergens are sensitized to cats and 27% to dogs. This document is intended to be a useful tool for clinicians involved in the management of people with dog or cat allergy. It was prepared from a consensus process based on the RAND / UCLA method. Following a literature review, it proposes various recommendations concerning the diagnosis and treatment of these patients, grounded in evidence and clinical experience. The diagnosis of dog and cat allergy is based on a medical history and physical examination that are consistent with each other and is confirmed with positive results on specific IgE skin tests. Sometimes, especially in polysensitized patients, molecular diagnosis is strongly recommended. Although the most advisable measure would be to avoid the animal, this is often impossible and associated with a major emotional impact. Furthermore, indirect exposure to allergens occurs in environments in which animals are not present. Immunotherapy is emerging as a potential solution to this problem, although further supporting studies are needed.
Prevalence of pollen‐induced allergic rhinitis with high pollen exposure in grasslands of northern China
Authors: X.‐Y. Wang, T.‐T. Ma, X.‐Y. Wang, Y. Zhuang, X.‐D. Wang, H.‐Y. Ning, H.‐Y. Shi, R.‐L. Yu, D. Yan, H.‐D. Huang, Y.‐F. Bai, G.‐L. Shan, B. Zhang, Q.‐K. Song, Y.‐F. Zhang, T.‐J. Zhang, D.‐Z. Jia, X.‐L. Liu, Z.‐X. Kang, W.‐J. Yan, B.‐T. Yang, X.‐Z. Bao, S.‐H. Sun, F.‐F. Zhang, W.‐H. Yu, C.‐L. Bai, T. Wei, T. Yang, T.‐Q. Ma, X.‐B. Wu, J.‐G. Liu, H. Du, L. Zhang, Y. Yan, D.‐Y. Wang
Journal: Allergy (2018)

The aim of this study was to investigate the prevalence of epidemiologic and physician-diagnosed pollen-induced AR (PiAR) in the grasslands of northern China and to study the impact of the intensity and time of pollen exposure on PiAR prevalence.A multistage, clustered and proportionately stratified random sampling with a field interviewer-administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count.A total of 6043 subjects completed the study, with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P = .024), but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types, which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature, and precipitation (P < .05), but negatively with wind speed and pressure P < .05).Pollen-induced AR (PiAR) prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions.
Abstract 19391: Early Structural Valve Deterioration of Mitroflow Aortic Bioprosthesis : Mode, Incidence and Impact on Outcome in a Large Cohort of Patients
Authors: Thomas Sénage, Jean Christian Roussel, Yohann Foucher, Christian Perigaud, Antoine Mugniot, Thierry Le Tourneau
Journal: Circulation (2014)

Background:  Structural valve deterioration (SVD) is a major flaw of bioprostheses. The occurrence of early SVD has been suspected in the last models of Mitroflow bioprosthesis. We sought to assess the incidence, the mode and the impact of SVD on outcome in a large series of Mitroflow aortic valve replacement (AVR).   Methods and Results:  617 consecutive patients underwent AVR with a Mitroflow prosthesis (model 12A or LX) between 2002 and 2007. By echocardiography, 39 patients developed early SVD (1.66% per patient-year), mainly on a stenosis mode (n=36). Mean delay to SVD was only 3.8±1.4 years and five-years SVD-free survival was 91.6% [95%CI 88.7-94.7] for the whole cohort, 79.8% [71.2-89.4] and 94.0%[90.3-97.8] for 19 and 21 mm sizes, respectively. Among the 39 SVD, 13 patients (33%) had an accelerated SVD once mean gradient exceeded 30mmHg. Valve-related death was 46.2% in this SVD subgroup. Overall 5-years patient survival was 69.6%[65.7-73.9]. In multivariable analysis SVD was the main correlate factor of overall mortality (HR=7.7; [95% CI;4.4-13.6]).   Conclusion:  Early SVD is frequent in Mitroflow bioprosthesis (model 12A or LX), especially for small sizes (19 and 21 mm) and reduced overall survival. An unpredictable accelerated pattern of SVD constitutes a high life-threatening condition. Hence, a close follow-up with yearly echocardiography after Mitroflow implantation is advisable. An urgent redo surgery may be warranted in patients with severe SVD even still asymptomatic
Modeling Health Care Expenditures and Use
Authors: Partha Deb, Edward C. Norton
Journal: Annual Review of Public Health (2018)

Health care expenditures and use are challenging to model because these dependent variables typically have distributions that are skewed with a large mass at zero. In this article, we describe estimation and interpretation of the effects of a natural experiment using two classes of nonlinear statistical models: one for health care expenditures and the other for counts of health care use. We extend prior analyses to test the effect of the ACA's young adult expansion on three different outcomes: total health care expenditures, office-based visits, and emergency department visits. Modeling the outcomes with a two-part or hurdle model, instead of a single-equation model, reveals that the ACA policy increased the number of office-based visits but decreased emergency department visits and overall spending.
Regulatory Pathway for 3D Printing
Authors: Rebecca Voelker
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Improved Evaluation of Antivascular Cancer Therapy Using Constrained Tracer-Kinetic Modeling for Multiagent Dynamic Contrast-Enhanced MRI
Authors: Stefanie J. Hectors, Igor Jacobs, Jasper Lok, Johannes Peters, Johan Bussink, Freek J. Hoeben, Henk M. Keizer, Henk M. Janssen, Klaas Nicolay, Matthias C. Schabel, Gustav J. Strijkers
Journal: Cancer Research (2018)

Dynamic contrast-enhanced MRI (DCE-MRI) is a promising technique for assessing the response of tumor vasculature to antivascular therapies. Multiagent DCE-MRI employs a combination of low and high molecular weight contrast agents, which potentially improves the accuracy of estimation of tumor hemodynamic and vascular permeability parameters. In this study, we used multiagent DCE-MRI to assess changes in tumor hemodynamics and vascular permeability after vascular-disrupting therapy. Multiagent DCE-MRI (sequential injection of G5 dendrimer, G2 dendrimer, and Gd-DOTA) was performed in tumor-bearing mice before, 2 and 24 hours after treatment with vascular disrupting agent DMXAA or placebo. Constrained DCE-MRI gamma capillary transit time modeling was used to estimate flow F, blood volume fraction vb, mean capillary transit time tc, bolus arrival time td, extracellular extravascular fraction ve, vascular heterogeneity index α-1 (all identical between agents) and extraction fraction E (reflective of permeability), and transfer constant Ktrans (both agent-specific) in perfused pixels. F, vb, and α-1 decreased at both time points after DMXAA, whereas tc increased. E (G2 and G5) showed an initial increase, after which, both parameters restored. Ktrans (G2 and Gd-DOTA) decreased at both time points after treatment. In the control, placebo-treated animals, only F, tc, and Ktrans Gd-DOTA showed significant changes. Histologic perfused tumor fraction was significantly lower in DMXAA-treated versus control animals. Our results show how multiagent tracer-kinetic modeling can accurately determine the effects of vascular-disrupting therapy by separating simultaneous changes in tumor hemodynamics and vascular permeability.Significance: These findings describe a new approach to measure separately the effects of antivascular therapy on tumor hemodynamics and vascular permeability, which could help more rapidly and accurately assess the efficacy of experimental therapy of this class. Cancer Res; 78(6); 1561-70. ©2018 AACR.
HIV gp120 in the Lungs of Antiretroviral Therapy–treated Individuals Impairs Alveolar Macrophage Responses to Pneumococci
Authors: Paul J. Collini, Martin A. Bewley, Mohamed Mohasin, Helen M. Marriott, Robert F. Miller, Anna-Maria Geretti, Apostolos Beloukas, Athanasios Papadimitropoulos, Robert C. Read, Mahdad Noursadeghi, David H. Dockrell
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: People living with HIV are at significantly increased risk of invasive pneumococcal disease, despite long-term antiretroviral therapy (ART). The mechanism explaining this observation remains undefined.Objectives: To determine if apoptosis-associated microbicidal mechanisms, required to clear intracellular pneumococci that survive initial phagolysosomal killing, are perturbed.Methods: Alveolar macrophages (AM) were obtained by BAL from healthy donors or HIV-1–seropositive donors on long-term ART with undetectable plasma viral load. Monocyte-derived macrophages (MDM) were obtained from healthy donors and infected with HIV-1BaL or treated with gp120. Macrophages were challenged with opsonized serotype 2 Streptococcus pneumoniae and assessed for apoptosis, bactericidal activity, protein expression, and mitochondrial reactive oxygen species (mROS). AM phenotyping, ultrasensitive HIV-1 RNA quantification, and gp120 measurement were also performed in BAL.Measurements and Main Results: HIV-1BaL infection impaired apoptosis, induction of mROS, and pneumococcal killing by MDM. Apoptosis-associated pneumococcal killing was also reduced in AM from ART-treated HIV-1–seropositive donors. BAL fluid from these individuals demonstrated persistent lung CD8+ T lymphocytosis, and gp120 or HIV-1 RNA was also detected. Despite this, transcriptional activity in AM freshly isolated from people living with HIV was broadly similar to healthy volunteers. Instead, gp120 phenocopied the defect in pneumococcal killing in healthy MDM through post-translational modification of Mcl-1, preventing apoptosis induction, caspase activation, and increased mROS generation. Moreover, gp120 also inhibited mROS-dependent pneumococcal killing in MDM.Conclusions: Despite ART, HIV-1, via gp120, drives persisting innate immune defects in AM microbicidal mechanisms, enhancing susceptibility to pneumococcal disease.
Genomic Analyses and Precision Oncology in Gastroesophageal Cancer: Forwards or Backwards?
Authors: Raghav Sundar, Patrick Tan
Journal: Cancer Discovery (2018)

Abstract Summary: Gastroesophageal adenocarcinoma (GEA) comprises a myriad of distinct subtypes with significant interpatient, intrapatient, and intratumor heterogeneity. Strategies for tackling molecular heterogeneity will be essential for the success of GEA precision oncology—in this regard, blood-based “liquid biopsies” may provide broader views of the real-time genomic landscape of this disease, identifying actionable biomarkers and monitoring therapy resistance. Cancer Discov; 8(1); 14–6. ©2018 AACR. See related article by Pectasides et al., p. 37. See related article by Janjigian et al., p. 49.
Efficacy and Safety of Novel Targeted Drug' Apatinib in Relapse or Refractory Non-Hodgkin Lymphoma: An Open Label, Single-Armed, Exploratory Study
Authors: Ling Li, Sa Xiao, Ken H. Young, Lei Zhang, Xin Li, Xiaorui Fu, Zhaoming Li, Zhenchang Sun, Xudong Zhang, Jiaqin Yan, Feifei Nan, Yu Chang, Mengyuan Shi, Mingzhi Zhang
Journal: Blood (2017)
Neighborhood Interventions to Reduce Violence
Authors: Michelle C. Kondo, Elena Andreyeva, Eugenia C. South, John M. MacDonald, Charles C. Branas
Journal: Annual Review of Public Health (2018)

Violence is a widespread problem that affects the physical, mental, and social health of individuals and communities. Violence comes with an immense economic cost to its victims and society at large. Although violence interventions have traditionally targeted individuals, changes to the built environment in places where violence occurs show promise as practical, sustainable, and high-impact preventive measures. This review examines studies that use quasi-experimental or experimental designs to compare violence outcomes for treatment and control groups before and after a change is implemented in the built environment. The most consistent evidence exists in the realm of housing and blight remediation of buildings and land. Some evidence suggests that reducing alcohol availability, improving street connectivity, and providing green housing environments can reduce violent crimes. Finally, studies suggest that neither transit changes nor school openings affect community violence.
Why Are American Indians Dying Young?
Authors: Jennifer Abbasi
Journal: JAMA (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 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
LIGHT–HVEM signaling in keratinocytes controls development of dermatitis
Authors: Rana Herro, Jr-Wen Shui, Sonja Zahner, Daniel Sidler, Yuko Kawakami, Toshiaki Kawakami, Koji Tamada, Mitchell Kronenberg, Michael Croft
Journal: The Journal of Experimental Medicine (2018)

Dermatitis is often associated with an allergic reaction characterized by excessive type 2 responses leading to epidermal acanthosis, hyperkeratosis, and dermal inflammation. Although factors like IL-4, IL-13, and thymic stromal lymphopoietin (TSLP) are thought to be instrumental for the development of this type of skin disorder, other cytokines may be critical. Here, we show that the tumor necrosis factor (TNF) superfamily protein LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for binding to HVEM, a receptor expressed on T lymphocytes) is required for experimental atopic dermatitis, and LIGHT directly controls keratinocyte hyperplasia, and production of periostin, a matricellular protein that contributes to the clinical features of atopic dermatitis as well as other skin diseases such as scleroderma. Mice with a conditional deletion of the LIGHT receptor HVEM (herpesvirus entry mediator) in keratinocytes phenocopied LIGHT-deficient mice in exhibiting reduced epidermal thickening and dermal collagen deposition in a model of atopic dermatitis driven by house dust mite allergen. LIGHT signaling through HVEM in human epidermal keratinocytes directly induced proliferation and periostin expression, and both keratinocyte-specific deletion of HVEM or antibody blocking of LIGHT–HVEM interactions after disease onset prevented expression of periostin and limited atopic dermatitis symptoms. Developing reagents that neutralize LIGHT–HVEM signaling might be useful for therapeutic intervention in skin diseases where periostin is a central feature.