tbuckley/cabot-search huggingface dataset:
A novel whole blood gene expression signature for asthma, dermatitis, and rhinitis multimorbidity in children and adolescents
Authors: Nathanaël Lemonnier, Erik Melén, Yale Jiang, Stéphane Joly, Camille Ménard, Daniel Aguilar, Edna Acosta‐Perez, Anna Bergström, Nadia Boutaoui, Mariona Bustamante, Glorisa Canino, Erick Forno, Juan Ramon González, Judith Garcia‐Aymerich, Olena Gruzieva, Stefano Guerra, Joachim Heinrich, Inger Kull, Jesús Ibarluzea Maurolagoitia, Loreto Santa‐Marina Rodriguez, Elisabeth Thiering, Magnus Wickman, Cezmi Akdis, Mübeccel Akdis, Wei Chen, Thomas Keil, Gerard H. Koppelman, Valérie Siroux, Cheng‐Jian Xu, Pierre Hainaut, Marie Standl, Jordi Sunyer, Juan C. Celedón, Josep Maria Antó, Jean Bousquet
Journal: Allergy (2020)

Allergic diseases often occur in combination (multimorbidity). Human blood transcriptome studies have not addressed multimorbidity. Large-scale gene expression data were combined to retrieve biomarkers and signaling pathways to disentangle allergic multimorbidity phenotypes.Integrated transcriptomic analysis was conducted in 1233 participants with a discovery phase using gene expression data (Human Transcriptome Array 2.0) from whole blood of 786 children from three European birth cohorts (MeDALL), and a replication phase using RNA Sequencing data from an independent cohort (EVA-PR, n = 447). Allergic diseases (asthma, atopic dermatitis, rhinitis) were considered as single disease or multimorbidity (at least two diseases), and compared with no disease.Fifty genes were differentially expressed in allergic diseases. Thirty-two were not previously described in allergy. Eight genes were consistently overexpressed in all types of multimorbidity for asthma, dermatitis, and rhinitis (CLC, EMR4P, IL5RA, FRRS1, HRH4, SLC29A1, SIGLEC8, IL1RL1). All genes were replicated the in EVA-PR cohort. RT-qPCR validated the overexpression of selected genes. In MeDALL, 27 genes were differentially expressed in rhinitis alone, but none was significant for asthma or dermatitis alone. The multimorbidity signature was enriched in eosinophil-associated immune response and signal transduction. Protein-protein interaction network analysis identified IL5/JAK/STAT and IL33/ST2/IRAK/TRAF as key signaling pathways in multimorbid diseases. Synergistic effect of multimorbidity on gene expression levels was found.A signature of eight genes identifies multimorbidity for asthma, rhinitis, and dermatitis. Our results have clinical and mechanistic implications, and suggest that multimorbidity should be considered differently than allergic diseases occurring alone.
Including Second Impact Syndrome in Sports-Related Concussions Evidence Review—Reply
Authors: Frederick P. Rivara, Christopher C. Giza, Gerard A. Gioia
Journal: JAMA Pediatrics (2020)

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 Pediatrics 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 Pediatrics journal
Safety at the Time of the COVID-19 Pandemic: How to Keep Our Oncology Patients and Healthcare Workers Safe
Authors: Pelin Cinar, Timothy Kubal, Alison Freifeld, Asmita Mishra, Lawrence Shulman, James Bachman, Rafael Fonseca, Hope Uronis, Dori Klemanski, Kim Slusser, Matthew Lunning, Catherine Liu
Journal: Journal of the National Comprehensive Cancer Network (2020)

The novel coronavirus, SARS-CoV-2, was first detected as a respiratory illness in December 2019 in Wuhan City, China. Since then, coronavirus disease 2019 (COVID-19) has impacted every aspect of our lives worldwide. In a time when terms such as social distancing and flattening the curve have become a part of our vernacular, it is essential that we understand what measures can be implemented to protect our patients and healthcare workers. Undoubtedly, healthcare providers have had to rapidly alter care delivery models while simultaneously acknowledging the crucial unknowns of how these changes may affect clinical outcomes. This special feature reviews strategies on how to mitigate transmission of COVID-19 in an effort to reduce morbidity and mortality associated with the disease for patients with cancer without infection, for patients with cancer with COVID-19 infection, and for the healthcare workers caring for them, while continuing to provide the best possible cancer care. [Editor's Note: This article includes the most current information available at time of publication; however, recommendations regarding public safety and practice may change rapidly in this situation. Individuals should get the most up to date information from the CDC website.].
Case 12-2020: A 24-Year-Old Man with Fever, Cough, and Dyspnea
Authors: Nicolas Barros, Shaunagh McDermott, Alexandra K. Wong, Sarah E. Turbett
Journal: New England Journal of Medicine (2020)

A 24-year-old man presented to the hospital because of fever and rapidly progressive hypoxemic respiratory failure. Laboratory evaluation was notable for leukocytosis with bandemia and thrombocytopenia. Nine days before presentation, the patient had been camping in northern New England. Two weeks before presentation, he was bitten by a mouse. A diagnostic test was performed.
A 38-Year-Old Woman With Worsening Dyspnea After Giving Birth
Authors: Yong Zhan, Anthony V. Norman, Masashi Kawabori
Journal: JAMA Cardiology (2020)

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
Evidence for the rationalisation phenomenon is exaggerated
Authors: Tom Stafford
Journal: Behavioral and Brain Sciences (2020)

Abstract The evidence for rationalisation, which motivates the target article, is exaggerated. Experimental evidence shows that rationalisation effects are small rather than gross and, I argue, largely silent on the pervasiveness and persistence of the phenomenon. At least some examples taken to show rationalisation also have an interpretation compatible with deliberate, knowing reason-responsiveness on the part of participants.
TRPV4 helps Piezo1 put the squeeze on pancreatic acinar cells
Authors: Fred Gorelick, Michael H. Nathanson
Journal: Journal of Clinical Investigation (2020)

Alterations in calcium signaling in pancreatic acinar cells can result in pancreatitis. Although pressure changes in the pancreas can elevate cytosolic calcium (Ca2+) levels, it is not known how transient pressure-activated elevations in calcium can cause prolonged calcium changes and consequent pancreatitis. In this issue of the JCI, Swain et al. describe roles for the mechanically activated plasma membrane calcium channels Piezo1 and transient receptor potential vanilloid subfamily 4 (TRPV4) in acinar cells. The authors used genetic deletion models and cell culture systems to investigate calcium signaling. Notably, activation of the Piezo1-dependent TRPV4 pathway was independent of the cholecystokinin (CCK) stimulation pathway. These results elegantly resolve an apparent discrepancy in calcium signaling and the pathogenesis of pancreatitis in pancreatic acinar cells.
Managing the supportive care needs of those affected by COVID-19
Authors: Sabrina Bajwah, Andrew Wilcock, Richard Towers, Massimo Costantini, Claudia Bausewein, Steffen T. Simon, Elisabeth Bendstrup, Wendy Prentice, Miriam J. Johnson, David C. Currow, Michael Kreuter, Athol U. Wells, Surinder S. Birring, Polly Edmonds, Irene J. Higginson
Journal: European Respiratory Journal (2020)

<b>For patients with COVID-19, there is a moral obligation to provide good supportive care to prevent avoidable suffering. This article provides a succinct informative overview, clinical guidance and information sheets for both patients and families.</b>https://bit.ly/2UPFsOj
Abstract 2549: Allostatic conditions in human glioblastoma stem cells are maintained with the contribution of CLIC1 membrane protein functional expression
Authors: Ivan Verduci, Valentina Carlini, Federica Barbieri, Antonio Daga, Tullio Florio, Michele Mazzanti
Journal: Cancer Research (2019)

Abstract Allostasis is a cellular condition physiologically occurring during transient hyper-activated state of the cell. When stress is persistent, cells are unable to restore a basal homeostatic state and allostasis become chronic. Most of the cells are not able to cope with these prolonged conditions and die. Conversely, solid tumors reveal a persistent stress state strengthen by chronic overexpression of several elements and hyper-activation of intracellular pathways. In glioblastoma stem cells (GSCs), the most evident allostatic outcome is a high rate of cell division. Several proteins present in the allostatic GSC plasma membrane are deregulated in either expression or function. Altering any of these proteins disrupts the allostatic equilibrium, causing drastic functional changes and, in some cases, cell death. Several of these proteins, potentially used as valuable pharmacological targets, are also crucial for the physiological activity of the cells. Consequently, modifying their functions would affect the survival of both cancer and healthy cell population. On the contrary, chloride intracellular protein 1 (CLIC1) is active as a membrane charge carrier only during periods of chronic stress, while during homeostatic conditions it is essentially irrelevant. Inhibition of NADPH oxidase or the NHE1 proton pump, both overexpressed in CSCs, causes death of both GSCs and normal mesenchymal stem cells. Conversely, impairing CLIC1 activity delays GSC cycle progression but leaves healthy cells functions unaltered. Our work suggests that CLIC1 protein and its associated chloride permeability are a crucial element involved in the stabilization of GB CSC allostasis. (This work is supported by a GRANT from AIRC to MM) Citation Format: Ivan Verduci, Valentina Carlini, Federica Barbieri, Antonio Daga, Tullio Florio, Michele Mazzanti. Allostatic conditions in human glioblastoma stem cells are maintained with the contribution of CLIC1 membrane protein functional expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2549.
Prolonged Improvement in Patient-Reported Outcomes (PROs) and Well-being in Older Patients With Treatment-Naïve (TN) Chronic Lymphocytic Leukemia Treated With Ibrutinib (Ibr): 3-Year Follow-up of the RESONATE-2 Study
Authors: Alessandra Tedeschi, Carolyn Jane Owen, Tadeusz Robak, Paul M. Barr, Osnat Bairey, Peter Hillmen, Steven Coutre, Stephen Devereux, Sebastian Grosicki, Helen McCarthy, Jianyong Li, David Simpson, Tanya Siddiqi, Giri Iyer, Indu D. Lal, Jeremiah Trudeau, Sandra Dai, James P. Dean, Danelle F. James, Jan A. Burger, Paolo Ghia, Thomas J. Kipps
Journal: Blood (2017)
An Off-the-Shelf™ Fratricide-Resistant CAR-T for the Treatment of T Cell Hematologic Malignancies
Authors: Matt L Cooper, Jaebok Choi, Karl W. Staser, Julie Ritchey, Jessica Niswonger, Kayla Eckardt, Michael P Rettig, Wang Bing, Linda G Eissenberg, Armin Ghobadi, Leah Gehrs, Julie Prior, Samuel Achilefu, Christopher A Miller, Catrina Fronick, Julie O'Neal, Feng Gao, David M. Weinstock, Alejandro Gutierrez, Robert S Fulton, John F DiPersio
Journal: Blood (2017)
The global significance of PRISm: how data from low- and middle-income countries link physiology to inflammation
Authors: Peter Jackson, Trishul Siddharthan
Journal: European Respiratory Journal (2020)

<b>Does the high rate and unique risk factors of preserved ratio impaired spirometry in low- and middle-income countries have something to teach us about the physiology of this highly prevalent pattern?</b>http://bit.ly/2SsQjeG
Current perspective on eicosanoids in asthma and allergic diseases: EAACI Task Force consensus report, part I
Authors: Milena Sokolowska, G. Enrico Rovati, Zuzana Diamant, Eva Untersmayr, Jargen Schwarze, Zuzanna Lukasik, Florentina Sava, Alba Angelina, Oscar Palomares, Cezmi A. Akdis, Liam O’Mahony, Marek Sanak, Sven‐Erik Dahlen, Grzegorz Woszczek
Journal: Allergy (2020)

Eicosanoids are biologically active lipid mediators, comprising prostaglandins, leukotrienes, thromboxanes, and lipoxins, involved in several pathophysiological processes relevant to asthma, allergies, and allied diseases. Prostaglandins and leukotrienes are the most studied eicosanoids and established inducers of airway pathophysiology including bronchoconstriction and airway inflammation. Drugs inhibiting the synthesis of lipid mediators or their effects, such as leukotriene synthesis inhibitors, leukotriene receptors antagonists, and more recently prostaglandin D2 receptor antagonists, have been shown to modulate features of asthma and allergic diseases. This review, produced by an European Academy of Allergy and Clinical Immunology (EAACI) task force, highlights our current understanding of eicosanoid biology and its role in mediating human pathology, with a focus on new findings relevant for clinical practice, development of novel therapeutics, and future research opportunities.
Increasing trends of lymphogranuloma venereum among HIV-negative and asymptomatic men who have sex with men, the Netherlands, 2011 to 2017
Authors: Fleur van Aar, Michelle M Kroone, Henry JC de Vries, Hannelore M Götz, Birgit HB van Benthem
Journal: Eurosurveillance (2020)

IntroductionLymphogranuloma venereum (LGV), an invasive form of Chlamydia trachomatis infection, has been reported among (mainly HIV-positive) men who have sex with men (MSM) since 2003. In the Netherlands, LGV testing recommendations changed from selective to universal testing in 2015. Changes in tested populations could have led to incomparable LGV positivity rates over time.AimWe investigated LGV trends among MSM attending Centres for Sexual Health using surveillance data between 2011 and 2017.MethodsLGV positivity was calculated among MSM tested for rectal Chlamydia infection and MSM tested specifically for LGV. With multivariable logistic regression analysis, the association between years and LGV was adjusted for testing indicators and determinants.ResultsWe included 224,194 consultations. LGV increased from 86 in 2011 to 270 in 2017. Among LGV-positives, proportions of HIV-negative and asymptomatic MSM increased from 17.4% to 45.6% and from 31.4% to 49.3%, respectively, between 2011 and 2017. Among MSM tested for rectal chlamydia, LGV positivity increased from 0.12% to 0.33% among HIV-negatives and remained stable around 2.5% among HIV-positives. Among LGV-tested MSM, LGV positivity increased from 2.1% to 5.7% among HIV-negatives and from 15.1% to 22.1% among HIV-positives. Multivariable models showed increased odds ratios and significant positive associations between years and LGV.ConclusionsAlthough increased testing and changes in LGV incidence are difficult to disentangle, we found increasing LGV trends, especially when corrected for confounding. LGV was increasingly attributed to HIV-negative and asymptomatic MSM, among whom testing was previously limited. This stresses the importance of universal testing and continuous surveillance.
Neoadjuvant PROSTVAC prior to radical prostatectomy enhances T-cell infiltration into the tumor immune microenvironment in men with prostate cancer
Authors: Houssein Abdul Sater, Jennifer L Marté, Renee N Donahue, Beatriz Walter-Rodriguez, Christopher R Heery, Seth M Steinberg, Lisa M Cordes, Guinevere Chun, Fatima Karzai, Marijo Bilusic, Stephanie A Harmon, Ismail Baris Turkbey, Peter L Choyke, Jeffrey Schlom, William L Dahut, Ravi A Madan, Peter A Pinto, James L Gulley
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Clinical trials have shown the ability of therapeutic vaccines to generate immune responses to tumor-associated antigens (TAAs). What is relatively less known is if this translates into immune-cell (IC) infiltration into the tumor microenvironment. This study examined whether neoadjuvant prostate-specific antigen (PSA)-targeted vaccination with PROSTVAC could induce T-cell immunity, particularly at the tumor site. Methods An open-label, phase II study of neoadjuvant PROSTVAC vaccine enrolled 27 patients with localized prostate cancer awaiting radical prostatectomy (RP). We evaluated increases in CD4 and CD8 T-cell infiltrates (RP tissue vs baseline biopsies) using a six-color multiplex immunofluorescence Opal method. Antigen-specific responses were assessed by intracellular cytokine staining after in vitro stimulation of peripheral blood mononuclear cells with overlapping 15-mer peptide pools encoding the TAAs PSA, brachyury and MUC-1. Results Of 27 vaccinated patients, 26 had matched prevaccination (biopsy) and postvaccination (RP) prostate samples available for non-compartmentalized analysis (NCA) and compartmentalized analysis (CA). Tumor CD4 T-cell infiltrates were significantly increased in postvaccination RP specimens compared with baseline biopsies by NCA (median 176/mm² vs 152/mm²; IQR 136–317/mm² vs 69–284/mm²; p=0.0249; median ratio 1.20; IQR 0.64–2.25). By CA, an increase in both CD4 T-cell infiltrates at the tumor infiltrative margin (median 198/mm² vs 151/mm²; IQR 123–500/mm² vs 85–256/mm²; p=0.042; median ratio 1.44; IQR 0.59–4.17) and in CD8 T-cell infiltrates at the tumor core (median 140/mm² vs 105/mm²; IQR 91–175/mm² vs 83–163/mm²; p=0.036; median ratio 1.25; IQR 0.88–2.09) were noted in postvaccination RP specimens compared with baseline biopsies. A total of 13/25 patients (52%) developed peripheral T-cell responses to any of the three tested TAAs (non-neoantigens); five of these had responses to more than one antigen of the three evaluated. Conclusion Neoadjuvant PROSTVAC can induce both tumor immune response and peripheral immune response. Trial registration number NCT02153918 .
Point-of-care assay for drunken driving with Pd@Pt core-shell nanoparticles-decorated ploy(vinyl alcohol) aerogel assisted by portable pressure meter
Authors: Yu Zhang, Quanyi Liu, Chong-Bo Ma, Qingqing Wang, Meiting Yang, Yan Du
Journal: Theranostics (2020)

Alcohol abuse causes health problems and security accidents. A reliable and sensitive detection system for alcohol has been an instinctive demand in law enforcement and forensic. More efforts are demanded in developing new sensing strategy preferably with portable and non-invasive traits for the pushforward of point-of-care (POC) device popularization. Methods: We developed a POC diagnosis system for alcohol assay with the aid of alcohol oxidase (AOX) pre-joining in the system as well as Pd@Pt core-shell nanoparticles (abbreviated to Pd@Pt) that were decorated on ploy(vinyl alcohol) aerogel with amphiphilicity. Biological samples like saliva and whole blood can be absorbed by the aerogel in a quick process, in which the analyte would go through a transformation from alcohol, H2O2, to a final production of O2, causing an analyte dose-dependent signal change in the commercial portable pressure meter. The cascade reactions are readily catalyzed by AOX and Pd@Pt, of which the latter one possesses excellent peroxidase-like activity. Results: Our design has smartness embodied in the aerogel circumvents the interference from methanol which is more ready to be catalyzed by AOX. Under the optimal conditions, the limit of detection for alcohol was 0.50 mM in saliva, and is able to distinguish the driving under the influence (DUI) (1.74 mM in saliva) and driving while impaired (DWI) (6.95 mM in saliva) in the national standard of China. Conclusion: Our proof-of-concept study provides the possibility for the establishment of POC device for alcohol and other target detection, not only owing to the sensing qualification but also thanks to the architecture of such sensor that has great flexibility by replacing the AOX with glucose oxidase (GOX), thenceforth realizing the accurate detection of glucose in 0.5% whole blood sample. With the advantages of easy accessibility and anti-interference ability, our sensor exhibits great potential for quantitative diagnostics in biological system.
Early Hepatic Lesions Display Immature Tertiary Lymphoid Structures and Show Elevated Expression of Immune Inhibitory and Immunosuppressive Molecules
Authors: Maxime Meylan, Florent Petitprez, Laetitia Lacroix, Luca Di Tommaso, Massimo Roncalli, Antoine Bougoüin, Alexis Laurent, Giuliana Amaddeo, Daniele Sommacale, Hélène Regnault, Jonathan Derman, Cécile Charpy, Fouad Lafdil, Jean-Michel Pawlotsky, Catherine Sautès-Fridman, Wolf H. Fridman, Julien Calderaro
Journal: Clinical Cancer Research (2020)

The impact of tertiary lymphoid structures (TLS) in hepatocellular carcinoma (HCC) progression is being extensively investigated. However, their presence during the early steps of human liver carcinogenesis remains unknown. We thus aimed to determine whether TLS are induced in preneoplastic/early hepatic lesions (EHL), and whether they are associated with a particular immune profile.A series of 127 EHLs (low/high-grade dysplastic nodules, early HCC, and small and progressed HCC) was included in the study. TLSs were investigated by pathologic reviewing. Densities of immune cells were assessed using IHC. A subset of lesions was microdissected and gene expression profiling was performed with a custom NanoString panel.Compared with surrounding cirrhotic nodules, EHL of all stages displayed increased densities of T cells, B cells, and dendritic cells. Immature TLSs were identified in 24% of EHL. Gene expression profiling identified a subset of EHL with elevated mRNA levels of various cytokines involved in immune cells' recruitment and TLS induction. This subgroup of EHL also showed overexpression of genes related to T- and B-cells' activation and antigen presentation, as well as those related to immunosuppression and immune exhaustion.Local immune activation occurs in the very early steps of liver carcinogenesis; however, it may not be fully efficient and paradoxically favor immune evasion and progression to full-blown HCC. These results have implications for the development of anti-HCC chemopreventive strategies in cirrhotic patients.