tbuckley/cabot-search huggingface dataset:
Using data from food challenges to inform management of consumers with food allergy: A systematic review with individual participant data meta-analysis
Authors: Nandinee Patel, Daniel C. Adelman, Katherine Anagnostou, Joseph L. Baumert, W. Marty Blom, Dianne E. Campbell, R. Sharon Chinthrajah, E.N. Clare Mills, Bushra Javed, Natasha Purington, Benjamin C. Remington, Hugh A. Sampson, Alexander D. Smith, Ross A.R. Yarham, Paul J. Turner
Journal: Journal of Allergy and Clinical Immunology (2021)

Eliciting doses (EDs) (eg, ED01 or ED05 values, which are the amounts of allergen expected to cause objective symptoms in 1% and 5% of the population with an allergy, respectively) are increasingly being used to inform allergen labeling and clinical management. These values are generated from food challenge, but the frequency of anaphylaxis in response to these low levels of allergen exposure and their reproducibility are unknown.Our aim was to determine (1) the rate of anaphylaxis in response to low-level peanut exposure and (2) the reproducibility of reaction thresholds (and anaphylaxis) at food challenge.We conducted a systematic review and individual participant data meta-analysis of studies that reported at least 50 individuals with peanut allergy reacting to peanut at double-blind, placebo-controlled food challenge (DBPCFC) and were published between January 2010 and September 2020. Risk of bias was assessed by using National Institute for Clinical Excellence methodologic checklists.A total of 19 studies were included (covering a total of 3151 participants, 534 of whom subsequently underwent further peanut challenge). At individual participant data meta-analysis, 4.5% (95% CI, 1.9% to 10.1%) of individuals reacted to 5 mg or less of peanut protein with anaphylaxis (moderate heterogeneity [I2 = 57%]). Intraindividual thresholds varied by up to 3 logs, although this variation was limited to a half-log change in 71.2% (95% CI, 56.2% to 82.6%) of individuals. In all, 2.4% (95% CI, 1.1% to 5.0%) of patients initially tolerated 5 mg of peanut protein but then reacted to this dose at subsequent challenge (low heterogeneity [I2 = 16%]); none developed anaphylaxis.Around 5% of individuals reacting to an ED01 or ED05 level of exposure to peanut might develop anaphylaxis in response to that dose. This equates to 1 and 6 anaphylaxis events per 2500 patients exposed to an ED01 or ED05 dose, respectively, in the broader population of individuals with peanut allergy.
OGP: A Repository of Experimentally Characterized <i>O</i>-Glycoproteins to Facilitate Studies on <i>O</i>-Glycosylation
Authors: Jiangming Huang, Mengxi Wu, Yang Zhang, Siyuan Kong, Mingqi Liu, Biyun Jiang, Pengyuan Yang, Weiqian Cao
Journal: Genomics Proteomics & Bioinformatics (2021)

Numerous studies on cancers, biopharmaceuticals, and clinical trials have necessitated comprehensive and precise analysis of protein O-glycosylation. However, the lack of updated and convenient databases deters the storage of and reference to emerging O-glycoprotein data. To resolve this issue, an O-glycoprotein repository named OGP was established in this work. It was constructed with a collection of O-glycoprotein data from different sources. OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far. Based on the recorded O-glycosylation sites, an O-glycosylation site prediction tool was developed. Moreover, an OGP-based website is already available (https://www.oglyp.org/). The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission. The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites. O-glycosylation data mining can be performed efficiently on this website, which will greatly facilitate related studies. In addition, the database is accessible from OGP website (https://www.oglyp.org/download.php).
Biocompatible AIEgen/p-glycoprotein siRNA@reduction-sensitive paclitaxel polymeric prodrug nanoparticles for overcoming chemotherapy resistance in ovarian cancer
Authors: Jun Wu, Quan Wang, Xiaoqi Dong, Min Xu, Juliang Yang, Xiaoqing Yi, Biao Chen, Xiyuan Dong, Ying Wang, Xiaoding Lou, Fan Xia, Shixuan Wang, Jun Dai
Journal: Theranostics (2021)

Nanoparticle drug delivery system (NDDS) is quite different from the widely studied traditional chemotherapy which suffers from drug resistance and side effect. NDDS offers the straightforward solution to the chemotherapy problem and provides an opportunity to monitor the drug delivery process in real time. In this vein, we developed one NDDS, namely Py-TPE/siRNA@PMP, to relieve resistance and side effects during chemotherapy against ovarian cancer. The Py-TPE/siRNA@PMP is a multifunctional polymeric nanoparticle contained several parts as follows: (1) a nanoparticle (NP) self-assembled by reduction-sensitive paclitaxel polymeric prodrug (PMP); (2) the glutathione (GSH)-responsive release of paclitaxel (PTX) for the suppression of ovarian cancer cells; (3) the P-glycoprotein (P-gp) siRNA for restoring the sensitivity of chemo-resistant tumor cells to chemotherapy; (4) the positively charged aggregation-induced emission fluorogen (AIEgen) Py-TPE for tumor imaging and promoting encapsulation of siRNA into the nanoparticle.
Combination of vasculature targeting, hypofractionated radiotherapy, and immune checkpoint inhibitor elicits potent antitumor immune response and blocks tumor progression
Authors: Stefano Pierini, Abhishek Mishra, Renzo Perales-Linares, Mireia Uribe-Herranz, Silvia Beghi, Andrea Giglio, Sergei Pustylnikov, Francesca Costabile, Stavros Rafail, Augusto Amici, John G Facciponte, Costantinos Koumenis, Andrea Facciabene
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Tumor endothelial marker 1 (TEM1) is a protein expressed in the tumor-associated endothelium and/or stroma of various types of cancer. We previously demonstrated that immunization with a plasmid-DNA vaccine targeting TEM1 reduced tumor progression in three murine cancer models. Radiation therapy (RT) is an established cancer modality used in more than 50% of patients with solid tumors. RT can induce tumor-associated vasculature injury, triggering immunogenic cell death and inhibition of the irradiated tumor and distant non-irradiated tumor growth (abscopal effect). Combination treatment of RT with TEM1 immunotherapy may complement and augment established immune checkpoint blockade. Methods Mice bearing bilateral subcutaneous CT26 colorectal or TC1 lung tumors were treated with a novel heterologous TEM1-based vaccine, in combination with RT, and anti-programmed death-ligand 1 (PD-L1) antibody or combinations of these therapies, tumor growth of irradiated and abscopal tumors was subsequently assessed. Analysis of tumor blood perfusion was evaluated by CD31 staining and Doppler ultrasound imaging. Immunophenotyping of peripheral and tumor-infiltrating immune cells as well as functional analysis was analyzed by flow cytometry, ELISpot assay and adoptive cell transfer (ACT) experiments. Results We demonstrate that addition of RT to heterologous TEM1 vaccination reduces progression of CT26 and TC1 irradiated and abscopal distant tumors as compared with either single treatment. Mechanistically, RT increased major histocompatibility complex class I molecule (MHCI) expression on endothelial cells and improved immune recognition of the endothelium by anti-TEM1 T cells with subsequent severe vascular damage as measured by reduced microvascular density and tumor blood perfusion. Heterologous TEM1 vaccine and RT combination therapy boosted tumor-associated antigen (TAA) cross-priming (ie, anti-gp70) and augmented programmed cell death protein 1 (PD-1)/PD-L1 signaling within CT26 tumor. Blocking the PD-1/PD-L1 axis in combination with dual therapy further increased the antitumor effect and gp70-specific immune responses. ACT experiments show that anti-gp70 T cells are required for the antitumor effects of the combination therapy. Conclusion Our findings describe novel cooperative mechanisms between heterologous TEM1 vaccination and RT, highlighting the pivotal role that TAA cross-priming plays for an effective antitumor strategy. Furthermore, we provide rationale for using heterologous TEM1 vaccination and RT as an add-on to immune checkpoint blockade as triple combination therapy into early-phase clinical trials.
Mitochondrial protein IF1 is a potential regulator of glucagon-like peptide (GLP-1) secretion function of the mouse intestine
Authors: Ying Wang, Jiaojiao Zhang, Xinyu Cao, Yaya Guan, Shuang Shen, Genshen Zhong, Xiwen Xiong, Yanhong Xu, Xiaoying Zhang, Hui Wang, Jianping Ye
Journal: Acta Pharmaceutica Sinica B (2021)

IF1 (ATPIF1) is a nuclear DNA-encoded mitochondrial protein whose activity is inhibition of the F1Fo-ATP synthase to control ATP production. IF1 activity remains unknown in the regulation of GLP-1 activity. In this study, IF1 was examined in the diet-induced obese mice using the gene knockout (If1-KO) mice. The mice gained more body weight on a high fat diet without a change in food intake. Insulin tolerance was impaired, but the oral glucose tolerance was improved through an increase in GLP-1 secretion. The KO mice exhibited an improved intestine structure, mitochondrial superstructure, enhanced mitophagy, reduced apoptosis and decreased adenine nucleotide translocase 2 (ANT2) protein in the intestinal epithelial cells together with preserved gut microbiota. The data suggest that GLP-1 secretion was enhanced in the obese If1-KO mice to preserve glucose tolerance through a signaling pathway of ANT2/mitochondria/L-cells/GLP-1/insulin. IF1 is a potential mitochondrial target for induction of GLP-1 secretion in L-cells.
COVID‐19 and Liver Cirrhosis: Focus on the Nonclassical Renin‐Angiotensin System and Implications for Therapy
Authors: Giovanni Sansoè, Manuela Aragno, Florence Wong
Journal: Hepatology (2021)

1Division of GastroenterologyHumanitas InstituteGradenigo HospitalTorinoItaly 2Department of Clinical and Biological SciencesUniversity of TorinoTorinoItaly 3Department of MedicineUniversity of TorontoToronto General HospitalTorontoOntarioCanada *ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO: Florence Wong, M.B.B.S., M.D., F.R.A.C.P., F.R.C.P.C. Division of Gastroenterology & Hepatology, Department of Medicine, University of Toronto, 9EN/222 Toronto General Hospital 200 Elizabeth St. Toronto M5G2C4, Ontario, Canada E‐mail: [email protected] Tel.: +1‐416‐340‐3834
Deep-learning-assisted analysis of echocardiographic videos improves predictions of all-cause mortality
Authors: Alvaro E. Ulloa Cerna, Linyuan Jing, Christopher W. Good, David P. vanMaanen, Sushravya Raghunath, Jonathan D. Suever, Christopher D. Nevius, Gregory J. Wehner, Dustin N. Hartzel, Joseph B. Leader, Amro Alsaid, Aalpen A. Patel, H. Lester Kirchner, John M. Pfeifer, Brendan J. Carry, Marios S. Pattichis, Christopher M. Haggerty, Brandon K. Fornwalt
Journal: Nature Biomedical Engineering (2021)
Serum paraprotein persistence and size determine outcome in a cohort of patients with a modern definition of plasmacytoma with up to 19 years of follow up
Authors: Elisabet E. Manasanch, Chutima Kunacheewa, Catherine M. Claussen, Hans C. Lee, Sheeba K. Thomas, Jill Gunther, Chelsea C. Pinnix, Bouthaina S. Dabaja, Behrang Amini, Raymond Alexanian, Robert Z. Orlowski, Wenli Dong, Lei Feng, Donna M. Weber
Journal: Blood Cancer Journal (2021)

Dear Editor
Endotyping chronic rhinosinusitis based on olfactory cleft mucus biomarkers
Authors: Zachary M. Soler, Rodney J. Schlosser, Todd E. Bodner, Jeremiah A. Alt, Vijay R. Ramakrishnan, Jose L. Mattos, Jennifer K. Mulligan, Jess C. Mace, Timothy L. Smith
Journal: Journal of Allergy and Clinical Immunology (2021)
American College of Rheumatology, American Academy of Dermatology, Rheumatologic Dermatology Society, and American Academy of Ophthalmology 2020 Joint Statement on Hydroxychloroquine Use With Respect to Retinal Toxicity
Authors: James T. Rosenbaum, Karen H. Costenbader, Julianna Desmarais, Ellen M. Ginzler, Nicole Fett, Susan M. Goodman, James R. O’Dell, Gabriela Schmajuk, Victoria P. Werth, Ronald B. Melles, Michael F. Marmor
Journal: Arthritis & Rheumatology (2021)

Four major medical societies involved with hydroxychloroquine (HCQ) therapy concur on the need for common principles and cooperation to minimize the risk of ocular toxicity. At a daily dosage of ≤5 mg/kg/day actual body weight, the risk of retinal toxicity from HCQ is <2% for usage up to 10 years. Widespread adoption of more sensitive testing techniques, such as optical coherence tomography and automated visual fields, by eye care providers will allow the detection of early toxicity and thus preserve the patient's visual function. Baseline testing is advised to rule out confounding disease when a patient is started on HCQ. Annual screening with sensitive tests should begin no more than 5 years after treatment initiation. Providers should be sensitive to the medical value of HCQ, and not stop the drug for uncertain indications. It is important to note that effective communication among prescribing physicians, patients, and eye care providers will optimize the utility and safety of HCQ.
Rapid crowdsourced innovation for COVID-19 response and economic growth
Authors: Khalil B. Ramadi, Freddy T. Nguyen
Journal: npj Digital Medicine (2021)

The COVID-19 pandemic has profoundly affected life worldwide. Governments have been faced with the formidable task of implementing public health measures, such as social distancing, quarantines, and lockdowns, while simultaneously supporting a sluggish economy and stimulating research and development (R&D) for the pandemic. Catalyzing bottom-up entrepreneurship is one method to achieve this. Home-grown efforts by citizens wishing to contribute their time and resources to help have sprouted organically, with ideas shared widely on the internet. We outline a framework for structured, crowdsourced innovation that facilitates collaboration to tackle real, contextualized problems. This is exemplified by a series of virtual hackathon events attracting over 9000 applicants from 142 countries and 49 states. A hackathon is an event that convenes diverse individuals to crowdsource solutions around a core set of predetermined challenges in a limited amount of time. A consortium of over 100 partners from across the healthcare spectrum and beyond defined challenges and supported teams after the event, resulting in the continuation of at least 25% of all teams post-event. Grassroots entrepreneurship can stimulate economic growth while contributing to broader R&D efforts to confront public health emergencies.
Demographic Characteristics of Persons Vaccinated During the First Month of the COVID-19 Vaccination Program — United States, December 14, 2020–January 14, 2021
Authors: Elizabeth M. Painter, Emily N. Ussery, Anita Patel, Michelle M. Hughes, Elizabeth R. Zell, Danielle L. Moulia, Lynn Gibbs Scharf, Michael Lynch, Matthew D. Ritchey, Robin L. Toblin, Bhavini Patel Murthy, LaTreace Q. Harris, Annemarie Wasley, Dale A. Rose, Amanda Cohn, Nancy E. Messonnier
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

In December 2020, two COVID-19 vaccines (Pfizer-BioNTech and Moderna) were authorized for emergency use in the United States for the prevention of coronavirus disease 2019 (COVID-19).* Because of limited initial vaccine supply, the Advisory Committee on Immunization Practices (ACIP) prioritized vaccination of health care personnel
Adalimumab and infliximab survival in patients with hidradenitis suppurativa: a daily practice cohort study*
Authors: L.M. Prens, K. Bouwman, P. Aarts, S. Arends, K.R. van Straalen, K. Dudink, B. Horváth, E.P. Prens
Journal: British Journal of Dermatology (2021)

Background Biologics are often required for the treatment of hidradenitis suppurativa (HS). However, data on the drug survival of biologics in daily practice are currently lacking. Objectives To assess the drug survival of antitumour necrosis factor biologics in a daily practice cohort of patients with HS and to identify predictors for drug survival. Methods A retrospective multicentre study was performed in two academic dermatology centres in the Netherlands. Adult patients with HS using biologics between 2008 and 2020 were included. Drug survival was analysed with Kaplan–Meier survival curves and predictors of survival with univariate Cox regression analysis. Results The overall drug survival of adalimumab (n = 104) at 12 and 24 months was 56·3% and 30·5%, respectively, which was predominantly determined by infectiveness. Older age (P = 0·02) and longer disease duration (P < 0·01) were associated with longer survival time. For infliximab (n = 44), overall drug survival was 58·3% and 48·6% at 12 and 24 months, respectively, and was predominantly determined by infectiveness and side-effects. Surgery during treatment was associated with a longer survival time (P = 0·01). Conclusions Survival rates were comparable for adalimumab and infliximab at 12 months, and were mainly determined by ineffectiveness. Age, disease duration (adalimumab) and surgery (infliximab) are predictors for longer survival.
Pragmatic Solutions to Counteract the Regressive Effects of the COVID-19 Pandemic for Women in Academic Oncology
Authors: Bridget Keenan, Reshma Jagsi, Katherine Van Loon
Journal: JAMA Oncology (2021)

This Viewpoint describes how pandemic-related disruptions may adversely effect progress toward a gender-balanced workforce in academic oncology and offers possible solutions to mitigate the problem in this specialty.
Targeting human plasmacytoid dendritic cells through BDCA2 prevents skin inflammation and fibrosis in a novel xenotransplant mouse model of scleroderma
Authors: Rebecca L Ross, Clarissa Corinaldesi, Gemma Migneco, Ian M Carr, Agne Antanaviciute, Christopher W Wasson, Antonio Carriero, Jörg H W Distler, Steve Holmes, Yasser M El-Sherbiny, Clive S McKimmie, Francesco Del Galdo
Journal: Annals of the Rheumatic Diseases (2021)

Objectives Plasmacytoid dendritic cells (pDC) have been implicated in the pathogenesis of autoimmune diseases, such as scleroderma (SSc). However, this has been derived from indirect evidence using ex vivo human samples or mouse pDC in vivo . We have developed human-specific pDC models to directly identify their role in inflammation and fibrosis, as well as attenuation of pDC function with BDCA2-targeting to determine its therapeutic application. Methods RNAseq of human pDC with TLR9 agonist ODN2216 and humanised monoclonal BDCA2 antibody, CBS004. Organotypic skin rafts consisting of fibroblasts and keratinocytes were stimulated with supernatant from TLR9-stimulated pDC and with CBS004. Human pDC were xenotransplanted into Nonobese diabetic/severe combined immunodeficiency (NOD SCID) mice treated with Aldara (inflammatory model), or bleomycin (fibrotic model) with CBS004 or human IgG control. Skin punch biopsies were used to assess gene and protein expression. Results RNAseq shows TLR9-induced activation of human pDC goes beyond type I interferon (IFN) secretion, which is functionally inactivated by BDCA2-targeting. Consistent with these findings, we show that BDCA2-targeting of pDC can completely suppress in vitro skin IFN-induced response. Most importantly, xenotransplantation of human pDC significantly increased in vivo skin IFN-induced response to TLR agonist and strongly enhanced fibrotic and immune response to bleomycin compared with controls. In these contexts, BDCA2-targeting suppressed human pDC-specific pathological responses. Conclusions Our data indicate that human pDC play a key role in inflammation and immune-driven skin fibrosis, which can be effectively blocked by BDCA2-targeting, providing direct evidence supporting the development of attenuation of pDC function as a therapeutic application for SSc.
Is the Dinoflagellate <i>Amoebophrya</i> Really Missing an mtDNA?
Authors: Ehsan Kayal, David R Smith
Journal: Molecular Biology and Evolution (2021)

Mitochondrial DNA (mtDNA) is a universal hallmark of aerobic eukaryotes. That is why the recent suggestion by John et al. (2019. An aerobic eukaryotic parasite with functional mitochondria that likely lacks a mitochondrial genome. Sci Adv. 5(4):eaav1110.) that the aerobic dinoflagellate Amoebophrya sp. strain AT5 (Syndiniales) lacks mtDNA was so remarkable. Here, by reanalyzing recently published genomic and transcriptomic data from three Amoebophrya strains, we provide evidence of a cryptic, highly reduced mtDNA in this clade. More work is needed before one can definitively say if Amoebophrya has or does not have an mtDNA, but for now, the data are pointing toward the existence of one. Ultimately, we urge caution when basing supposedly absent genomic features on single line evidences.
ICPM NEWS: The European Training Network ETUDE (Encompassing Training in Functional Disorders across Europe) Is Recruiting 15 Early-Stage Researchers
Authors: J.G.M. Rosmalen, C. Burton, A. Carson, Fiammetta Cosci, L. Frostholm, N. Lehnen, T. Olde Hartman, C. Rask, J. Rymaszewska, J. Stone, L. Tak, M. Witthöft, B. Löwe
Journal: Psychotherapy and Psychosomatics (2021)
Single-cell analysis of human B cell maturation predicts how antibody class switching shapes selection dynamics
Authors: Hamish W. King, Nara Orban, John C. Riches, Andrew J. Clear, Gary Warnes, Sarah A. Teichmann, Louisa K. James
Journal: Science Immunology (2021)

Integrated single-cell transcriptomic and BCR analyses reveal how antibody class switching influences human B cell fate and function.
Urban–Rural Mortality Disparities from Chronic Lower Respiratory Diseases in the United States, 1999–2019
Authors: Paul A. Reyfman, Basil Khuder, Jacob B. Pierce, Daniel A. Meza, Mercedes R. Carnethon, Ravi Kalhan, Sadiya S. Khan
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Urban–Rural Mortality Disparities from Chronic Lower Respiratory Diseases in the United States, 1999–2019." American Journal of Respiratory and Critical Care Medicine, 203(11), pp. 1435–1437