tbuckley/cabot-search huggingface dataset:
α-Gal specific-IgE prevalence and levels in Ecuador and Kenya: Relation to diet, parasites, and IgG4
Authors: Jeffrey M. Wilson, Behnam Keshavarz, Hayley R. James, Maya K.C. Retterer, Alexander J. Schuyler, Alice Knoedler, Lisa J. Workman, Lucy Ng’ang’a, Martha E. Chico, Eva Rönmark, Peter W. Heymann, Matthew S. Perzanowski, Thomas A.E. Platts-Mills, Philip J. Cooper
Journal: Journal of Allergy and Clinical Immunology (2021)
HLA-G/LILRBs: A Cancer Immunotherapy Challenge
Authors: Edgardo D. Carosella, Silvia Gregori, Diana Tronik-Le Roux
Journal: Trends in cancer (2021)

Despite some success, many patients do not benefit from immunotherapy. New strategies to improve clinical efficacy include identification of novel immune-checkpoint (IC) targets or a combination of immunotherapy with antiangiogenic treatments. Here, we propose the therapeutic use of IC, HLA-G/LILRB, and explore its enhanced synergistic antitumor activity when combined with antiangiogenic therapies.
COVID-19 in immunocompromised patients: A systematic review of cancer, hematopoietic cell and solid organ transplant patients
Authors: Jennifer A. Belsky, Brian P. Tullius, Margaret G. Lamb, Rouba Sayegh, Joseph R. Stanek, Jeffery J. Auletta
Journal: Journal of Infection (2021)

BackgroundThe clinical impact of severe coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in immunocompromised patients has not been systematically evaluated.MethodsWe reviewed current literature reporting on COVID-19 in cancer (CA), hematopoietic cell (HCT), and solid organ transplant (SOT) patients and compared their clinical data and outcomes to the general population. For adult CA, HCT and SOT patients, an extensive search strategy retrieved all articles published until July 20, 2020 by combining the terms coronavirus, coronavirus infection, COVID-19, and SARS-CoV-2 in PubMed, Cochrane, and Web of Science, and following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. For the pediatric CA cohort, a global COVID-19 registry was used. For the general population cohort, a large meta-analysis was used to compare pooled prevalence estimates, and two large meta-analyses were utilized to serve as pooled comparators for hospitalized COVID-19 patients.FindingsCompared to the general population, adult CA and SOT patients with COVID-19 had higher comorbidities, greater levels of inflammatory markers at diagnosis, and higher rates of intensive care and hospital mortality. Pediatric CA patients and HCT patients with COVID-19 tended to have clinical presentations and outcomes similar to the general population.InterpretationTo our knowledge, this is the first systematic review evaluating COVID-19 phenotype and outcomes in immunocompromised patients and comparing them to the general population, which shows that hospital outcomes appear to be worse in adult CA and SOT patients, potentially due to their higher co-morbidity burden.FundingNone
Diversification of CD1 Molecules Shapes Lipid Antigen Selectivity
Authors: Nicole M Paterson, Hussein Al-Zubieri, Matthew F Barber
Journal: Molecular Biology and Evolution (2021)

Molecular studies of host-pathogen evolution have largely focused on the consequences of variation at protein-protein interaction surfaces. The potential for other microbe-associated macromolecules to promote arms race dynamics with host factors remains unclear. The cluster of differentiation 1 (CD1) family of vertebrate cell surface receptors plays a crucial role in adaptive immunity through binding and presentation of lipid antigens to T-cells. Although CD1 proteins present a variety of endogenous and microbial lipids to various T-cell types, they are less diverse within vertebrate populations than the related major histocompatibility complex (MHC) molecules. We discovered that CD1 genes exhibit a high level of divergence between simian primate species, altering predicted lipid-binding properties and T-cell receptor interactions. These findings suggest that lipid-protein conflicts have shaped CD1 genetic variation during primate evolution. Consistent with this hypothesis, multiple primate CD1 family proteins exhibit signatures of repeated positive selection at surfaces impacting antigen presentation, binding pocket morphology, and T-cell receptor accessibility. Using a molecular modeling approach, we observe that interspecies variation as well as single mutations at rapidly-evolving sites in CD1a drastically alter predicted lipid binding and structural features of the T-cell recognition surface. We further show that alterations in both endogenous and microbial lipid-binding affinities influence the ability of CD1a to undergo antigen swapping required for T-cell activation. Together these findings establish lipid-protein interactions as a critical force of host-pathogen conflict and inform potential strategies for lipid-based vaccine development.
Hierarchical tumor heterogeneity mediated by cell contact between distinct genetic subclones
Authors: Swathi Karthikeyan, Ian G. Waters, Lauren Dennison, David Chu, Joshua Donaldson, Dong Ho Shin, D. Marc Rosen, Paula I. Gonzalez-Ericsson, Violeta Sanchez, Melinda E. Sanders, Morgan V. Pantone, Riley E. Bergman, Brad A. Davidson, Sarah C. Reed, Daniel J. Zabransky, Karen Cravero, Kelly Kyker-Snowman, Berry Button, Hong Yuen Wong, Paula J. Hurley, Sarah Croessmann, Ben Ho Park
Journal: Journal of Clinical Investigation (2021)

Intratumor heterogeneity is an important mediator of poor outcomes in many cancers, including breast cancer. Genetic subclones frequently contribute to this heterogeneity; however, their growth dynamics and interactions remain poorly understood. PIK3CA and HER2 alterations are known to coexist in breast and other cancers. Herein, we present data that describe the ability of oncogenic PIK3CA mutant cells to induce the proliferation of quiescent HER2 mutant cells through a cell contact-mediated mechanism. Interestingly, the HER2 cells proliferated to become the major subclone over PIK3CA counterparts both in vitro and in vivo. Furthermore, this phenotype was observed in both hormone receptor-positive and -negative cell lines, and was dependent on the expression of fibronectin from mutant PIK3CA cells. Analysis of human tumors demonstrated similar HER2:PIK3CA clonal dynamics and fibronectin expression. Our study provides insight into nonrandom subclonal architecture of heterogenous tumors, which may aid the understanding of tumor evolution and inform future strategies for personalized medicine.
Regulatory B cells, A to Z
Authors: Kirstin Jansen, Lacin Cevhertas, Siyuan Ma, Pattraporn Satitsuksanoa, Mübeccel Akdis, Willem van de Veen
Journal: Allergy (2021)

B cells play a central role in the immune system through the production of antibodies. During the past two decades, it has become increasingly clear that B cells also have the capacity to regulate immune responses through mechanisms that extend beyond antibody production. Several types of human and murine regulatory B cells have been reported that suppress inflammatory responses in autoimmune disease, allergy, infection, transplantation, and cancer. Key suppressive molecules associated with regulatory B-cell function include the cytokines IL-10, IL-35, and TGF-β as well as cell membrane-bound molecules such as programmed death-ligand 1, CD39, CD73, and aryl hydrocarbon receptor. Regulatory B cells can be induced by a range of different stimuli, including microbial products such as TLR4 or TLR9 ligands, inflammatory cytokines such as IL-6, IL-1β, and IFN-α, as well as CD40 ligation. This review provides an overview of our current knowledge on regulatory B cells. We discuss different types of regulatory B cells, the mechanisms through which they exert their regulatory functions, factors that lead to induction of regulatory B cells and their role in the alteration of inflammatory responses in different diseases.
Myeloma-specific superenhancers affect genes of biological and clinical relevance in myeloma
Authors: Yunlu Jia, Jianbiao Zhou, Tze King Tan, Tae-Hoon Chung, Regina Wan Ju Wong, Jing-Yuan Chooi, Julia Sze Lynn Lim, Takaomi Sanda, Melissa Ooi, Sanjay De Mel, Cinnie Soekojo, Yongxia Chen, Enfan Zhang, Zhen Cai, Peng Shen, Jian Ruan, Wee-Joo Chng
Journal: Blood Cancer Journal (2021)

Abstract Multiple myeloma (MM) is an aggressive plasma cell neoplasm characterized by genomic heterogeneity. Superenhancers (SEs) are defined as large clusters of enhancers in close genomic proximity, which regulate genes for maintaining cellular identity and promote oncogenic transcription to which cancer cells highly addicted. Here, we analyzed cis -regulatory elements in MM samples with H3K27ac ChIP-seq, to identify novel SE-associated genes involved in the myeloma pathogenesis. SEs and their associated genes in cancerous tissue were compared with the control samples, and we found SE analysis alone uncovered cell-lineage-specific transcription factors and well-known oncogenes ST3GAL6 and ADM. Using a transcriptional CDK7 inhibitor, THZ1, coupled with H3K27ac ChlP-seq, we identified MAGI2 as a novel SE-associated gene of myeloma cells. Elevated MAGI2 was related to myelomagenesis with gradual increased expression from MGUS, SMM to newly diagnosed and relapsed MM. High prevalence of MAGI2 was also associated with poor survival of MM patients. Importantly, inhibition of the SE activity associated with MAGI2 decreased MAGI2 expression, inhibited cell growth and induced cell apoptosis. Mechanistically, we revealed that the oncogenic transcription factor, MAF, directly bound to the SE region and activated gene transcription. In summary, the discoveries of these acquired SEs-associated genes and the novel mechanism by which they are regulated provide new insights into MM biology and MAGI2-MAF-SE regulatory circuit offer potential novel targets for disease treatment.
Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial
Authors: Sandro Pignata, Domenica Lorusso, Florence Joly, Ciro Gallo, Nicoletta Colombo, Cristiana Sessa, Aristotelis Bamias, Vanda Salutari, Frédèric Selle, Simona Frezzini, Ugo De Giorgi, Patricia Pautier, Alessandra Bologna, Michele Orditura, Coraline Dubot, Angiolo Gadducci, Serafina Mammoliti, Isabelle Ray-Coquard, Elena Zafarana, Enrico Breda, Laure Favier, Antonio Ardizzoia, Saverio Cinieri, Rémy Largillier, Daniela Sambataro, Emmanuel Guardiola, Rossella Lauria, Carmela Pisano, Francesco Raspagliesi, Giovanni Scambia, Gennaro Daniele, Francesco Perrone, S Pignata, D Lorusso, F Joly, C Gallo, N Colombo, C Sessa, A Bamias, V Salutari, F Selle, S Frezzini, U De Giorgi, P Pautier, A Bologna, M Orditura, C Dubot, A Gadducci, S Mammoliti, I Ray-Coquard, E Zafarana, E Breda, L Favier, A Ardizzoia, S Cinieri, R Largillier, D Sambataro, E Guardiola, R Lauria, C Pisano, F Raspagliesi, G Scambia, G Daniele, F Perrone
Journal: The Lancet Oncology (2021)
ALLERGY TO DERMATOPHAGOIDES PTERONYSSINUS. MOLECULAR RECOGNITION PATTERN ATTRIBUTED TO DIFFERENT PATHOLOGIES
Authors: Fernando Pineda de la Losa, Ruperto González-Pérez, Miriam Castillo, Paloma Poza-Guedes, E. Mederos-Luis, C. Alava-Cruz, Victor Matheu, Inmaculada Sánchez-Machin
Journal: Journal of Allergy and Clinical Immunology (2021)
From the authors
Authors: X. Muñoz, F. Torres, G. Sampol
Journal: European Respiratory Journal (2008)

Hypercapnia as the influencing factor of pulse oximetryTo the Editors:We would like to comment on the recently published study by MUN ˜OZ et al. [1], which analysed accuracy and precision of pulse oximetry at different carbon dioxide arterial tension (Pa,CO 2 ) levels.Although the paper investigates an interesting hypothesis, significant limitations should be addressed.
Marrow transplantation with or without donor buffy coat cells for 65 transfused aplastic anemia patients
Authors: R Storb, KC Doney, ED Thomas, F Appelbaum, CD Buckner, RA Clift, HJ Deeg, BW Goodell, R Hackman, JA Hansen, J Sanders, K Sullivan, PL Weiden, RP Witherspoon
Journal: Blood (1982)
Incidence and Factors Associated With Androgenetic Alopecia Among Transgender and Gender-Diverse Patients Treated With Masculinizing Hormone Therapy
Authors: Nick Thoreson, Chris Grasso, Jennifer Potter, Dana S. King, J. Klint Peebles, Erica D. Dommasch
Journal: JAMA Dermatology (2021)

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Targeting Pan-ETS Factors Inhibits Melanoma Progression
Authors: Lee Huang, Yougang Zhai, Jennifer La, Jason W. Lui, Stephen P.G. Moore, Elizabeth C. Little, Sixia Xiao, Adil J. Haresi, Candice Brem, Jag Bhawan, Deborah Lang
Journal: Cancer Research (2021)

Abstract The failure of once promising target-specific therapeutic strategies often arises from redundancies in gene expression pathways. Even with new melanoma treatments, many patients are not responsive or develop resistance, leading to disease progression in terms of growth and metastasis. We previously discovered that the transcription factors ETS1 and PAX3 drive melanoma growth and metastasis by promoting the expression of the MET receptor. Here, we find that there are multiple ETS family members expressed in melanoma and that these factors have redundant functions. The small molecule YK-4-279, initially developed to target the ETS gene–containing translocation product EWS-FLI1, significantly inhibited cellular growth, invasion, and ETS factor function in melanoma cell lines and a clinically relevant transgenic mouse model, BrafCA;Tyr-CreERT2;Ptenf/f. One of the antitumor effects of YK-4-279 in melanoma is achieved via interference of multiple ETS family members with PAX3 and the expression of the PAX3-ETS downstream gene MET. Expression of exogenous MET provided partial rescue of the effects of YK-4-279, further supporting that MET loss is a significant contributor to the antitumor effects of the drug. This is the first study identifying multiple overlapping functions of the ETS family promoting melanoma. In addition, targeting all factors, rather than individual members, demonstrated impactful deleterious consequences in melanoma progression. Given that multiple ETS factors are known to have oncogenic functions in other malignancies, these findings have a high therapeutic impact. Significance: These findings identify YK-4-279 as a promising therapeutic agent against melanoma by targeting multiple ETS family members and blocking their ability to act as transcription factors.
COVID-19 in the Caribbean
Authors: Talha Khan Burki
Journal: The Lancet Respiratory Medicine (2021)

It had looked as if Barbados might avoid a destructive COVID-19 pandemic. The Caribbean nation, home to around 287 000 people, registered fewer than 400 cases of the disease for the whole of 2020. But January, 2021, saw a surge. By the end of the month, Barbados had registered well over 1000 new cases of COVID-19. On Feb 3, 2021, it went into lockdown. On the same day, Saint Lucia declared a state of emergency. It has confirmed more than three times as many cases of COVID-19 this year as it did last year.
Preclinical Evaluation of B7-H3–specific Chimeric Antigen Receptor T Cells for the Treatment of Acute Myeloid Leukemia
Authors: Eben I. Lichtman, Hongwei Du, Peishun Shou, Feifei Song, Kyogo Suzuki, Sarah Ahn, Guangming Li, Soldano Ferrone, Lishan Su, Barbara Savoldo, Gianpietro Dotti
Journal: Clinical Cancer Research (2021)

Abstract Purpose: The development of safe and effective chimeric antigen receptor (CAR) T-cell therapy for acute myeloid leukemia (AML) has largely been limited by the concomitant expression of most AML-associated surface antigens on normal myeloid progenitors and by the potential prolonged disruption of normal hematopoiesis by the immunotargeting of these antigens. The purpose of this study was to evaluate B7-homolog 3 (B7-H3) as a potential target for AML-directed CAR T-cell therapy. B7-H3, a coreceptor belonging to the B7 family of immune checkpoint molecules, is overexpressed on the leukemic blasts of a significant subset of patients with AML and may overcome these limitations as a potential target antigen for AML-directed CAR-T therapy. Experimental Design: B7-H3 expression was evaluated on AML cell lines, primary AML blasts, and normal bone marrow progenitor populations. The antileukemia efficacy of B7-H3–specific CAR-T cells (B7-H3.CAR-T) was evaluated using in vitro coculture models and xenograft models of disseminated AML, including patient-derived xenograft models. The potential hematopoietic toxicity of B7-H3.CAR-Ts was evaluated in vitro using colony formation assays and in vivo in a humanized mouse model. Results: B7-H3 is expressed on monocytic AML cell lines and on primary AML blasts from patients with monocytic AML, but is not significantly expressed on normal bone marrow progenitor populations. B7-H3.CAR-Ts exhibit efficient antigen-dependent cytotoxicity in vitro and in xenograft models of AML, and are unlikely to cause unacceptable hematopoietic toxicity. Conclusions: B7-H3 is a promising target for AML-directed CAR-T therapy. B7-H3.CAR-Ts control AML and have a favorable safety profile in preclinical models.
L'Union Européenne face au risque pandémique: réunion du groupe ad hoc " maladies transmissibles " de la DGV sur la grippe A(H5N1), Luxembourg, 14 janvier 1998
Authors: J C Desenclos, R Manigat
Journal: Eurosurveillance (1998)

La transmission d'un virus grippal aviaire H5N1 a un enfant a Hong Kong en mai 1997 suivie de la survenue de 17 autres cas humains avec un taux de letalite eleve (6/18, 33%) (1) pouvait faire evoquer l'imminence d'une pandemie de grippe et a amene plusieurs pays europeens a prendre certaines mesures.
Pharmacometabolomics of Meformin Demonstrated Insulin Sensitivity Related Pathways at Peak Plasma Concentration on Healthy Volunteers – Preliminary Results
Authors: Tee Khim Boon, Hasniza Zaman Huri, Najihah Mohd Hashim, Luqman Ibrahim, Mohd Zuwairi Saiman, Zaril Harza Zakaria, Kasful Asra Sakika, Syaza Fatnin Hisham, Azwa Mansor
Journal: Metabolism (2021)
Incorrect Data in Text
Journal: JAMA (2020)

US Preventive Services Task Force; Kirsten Bibbins-Domingo, PhD, MD, MAS; David C. Grossman, MD, MPH; Susan J. Curry, PhD; Karina W. Davidson, PhD, MASc; John W. Epling Jr, MD, MSEd; Francisco A. R. García, MD, MPH; Matthew W. Gillman, MD, SM; Alex R. Kemper, MD, MPH, MS; Alex H. Krist, MD, MPH; Ann E. Kurth, PhD, RN, MSN, MPH; C. Seth Landefeld, MD; Michael L. LeFevre, MD, MSPH; Carol M. Mangione, MD, MSPH; William R. Phillips, MD, MPH; Douglas K. Owens, MD, MS; Maureen G. Phipps, MD, MPH; Michael P. Pignone, MD, MPH
G protein-coupled receptor kinase 5 (GRK5) contributes to impaired cardiac function and immune cell recruitment in post-ischemic heart failure
Authors: Claudio de Lucia, Laurel A Grisanti, Giulia Borghetti, Michela Piedepalumbo, Jessica Ibetti, Anna Maria Lucchese, Eric W Barr, Rajika Roy, Ama Dedo Okyere, Haley Christine Murphy, Erhe Gao, Giuseppe Rengo, Steven R Houser, Douglas G Tilley, Walter J Koch
Journal: Cardiovascular Research (2021)

Abstract Aims Myocardial infarction (MI) is the most common cause of heart failure (HF) worldwide. G protein-coupled receptor kinase 5 (GRK5) is upregulated in failing human myocardium and promotes maladaptive cardiac hypertrophy in animal models. However, the role of GRK5 in ischemic heart disease is still unknown. In this study, we evaluated whether myocardial GRK5 plays a critical role post-MI in mice and included the examination of specific cardiac immune and inflammatory responses. Methods and results Cardiomyocyte-specific GRK5 overexpressing transgenic mice (TgGRK5) and non-transgenic littermate control (NLC) mice as well as cardiomyocyte-specific GRK5 knockout mice (GRK5cKO) and wild type (WT) were subjected to MI and, functional as well as structural changes together with outcomes were studied. TgGRK5 post-MI mice showed decreased cardiac function, augmented left ventricular dimension and decreased survival rate compared to NLC post-MI mice. Cardiac hypertrophy and fibrosis as well as fetal gene expression were increased post-MI in TgGRK5 compared to NLC mice. In TgGRK5 mice, GRK5 elevation produced immuno-regulators that contributed to the elevated and long-lasting leukocyte recruitment into the injured heart and ultimately to chronic cardiac inflammation. We found an increased presence of pro-inflammatory neutrophils and macrophages as well as neutrophils, macrophages and T-lymphocytes at 4-days and 8-weeks respectively post-MI in TgGRK5 hearts. Conversely, GRK5cKO mice were protected from ischemic injury and showed reduced early immune cell recruitment (predominantly monocytes) to the heart, improved contractility and reduced mortality compared to WT post-MI mice. Interestingly, cardiomyocyte-specific GRK2 transgenic mice did not share the same phenotype of TgGRK5 mice and did not have increased cardiac leukocyte migration and cytokine or chemokine production post-MI. Conclusions Our study shows that myocyte GRK5 has a crucial and GRK-selective role on the regulation of leucocyte infiltration into the heart, cardiac function and survival in a murine model of post-ischemic HF, supporting GRK5 inhibition as a therapeutic target for HF.
Associations of cereal grains intake with cardiovascular disease and mortality across 21 countries in Prospective Urban and Rural Epidemiology study: prospective cohort study
Authors: Sumathi Swaminathan, Mahshid Dehghan, John Michael Raj, Tinku Thomas, Sumathy Rangarajan, David Jenkins, Prem Mony, Viswanathan Mohan, Scott A Lear, Alvaro Avezum, Patricio Lopez-Jaramillo, Annika Rosengren, Fernando Lanas, Khalid F AlHabib, Antonio Dans, Mirac Vural Keskinler, Thandi Puoane, Biju Soman, Li Wei, Katarzyna Zatonska, Rafael Diaz, Noorhassim Ismail, Jephat Chifamba, Roya Kelishadi, Afzalhussein Yusufali, Rasha Khatib, Liu Xiaoyun, Hu Bo, Romaina Iqbal, Rita Yusuf, Karen Yeates, Koon Teo, Salim Yusuf
Journal: BMJ (2021)

Abstract Objective To evaluate the association between intakes of refined grains, whole grains, and white rice with cardiovascular disease, total mortality, blood lipids, and blood pressure in the Prospective Urban and Rural Epidemiology (PURE) study. Design Prospective cohort study. Setting PURE study in 21 countries. Participants 148 858 participants with median follow-up of 9.5 years. Exposures Country specific validated food frequency questionnaires were used to assess intakes of refined grains, whole grains, and white rice. Main outcome measure Composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios were estimated for associations of grain intakes with mortality, major cardiovascular events, and their composite by using multivariable Cox frailty models with random intercepts to account for clustering by centre. Results Analyses were based on 137 130 participants after exclusion of those with baseline cardiovascular disease. During follow-up, 9.2% (n=12 668) of these participants had a composite outcome event. The highest category of intake of refined grains (≥350 g/day or about 7 servings/day) was associated with higher risk of total mortality (hazard ratio 1.27, 95% confidence interval 1.11 to 1.46; P for trend=0.004), major cardiovascular disease events (1.33, 1.16 to 1.52; P for trend&lt;0.001), and their composite (1.28, 1.15 to 1.42; P for trend&lt;0.001) compared with the lowest category of intake (&lt;50 g/day). Higher intakes of refined grains were associated with higher systolic blood pressure. No significant associations were found between intakes of whole grains or white rice and health outcomes. Conclusion High intake of refined grains was associated with higher risk of mortality and major cardiovascular disease events. Globally, lower consumption of refined grains should be considered.