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Article ; Online: A Perspective on the Role of Point-of-Care “Immuno-Triaging” to Optimize COVID-19 Vaccination Distribution in a Time of Scarcity

Yi Zhang / Angela Rogers / Kari Nadeau / Jun Gu / Samuel Yang

Frontiers in Public Health, Vol

2021 Volume 9

Abstract: Vaccine bears hope to bring COVID-19 pandemic under control. With limited supply, vaccines must be utilized efficiently to provide protection to those who need it most. Currently, no practical framework has been proposed to ensure fair vaccine allocation ...

Abstract	Vaccine bears hope to bring COVID-19 pandemic under control. With limited supply, vaccines must be utilized efficiently to provide protection to those who need it most. Currently, no practical framework has been proposed to ensure fair vaccine allocation at individual level, which is a recognized problem. We propose here an evidence-based decision-making framework for COVID-19 vaccine appropriation that prioritizes vaccine doses to individuals based on their immunological status, or immuno-triaging. To ensure successful implementation of the proposed framework, point-of-care (POC) immunodiagnostic testing is needed to quickly ramp up the testing capability. Considerations for deploying POC immunodiagnostic testing at such a large scale are discussed. We hope that the proposed immunological decision-making framework for evidence-based COVID-19 vaccine appropriation provides an objective approach to ensure fair and efficient utilization of the scarce vaccine resource at the individual level that also maximizes the collective societal benefit.
Keywords	COVID-19 ; vaccine ; point-of-care ; immunodiagnostics ; vaccine distribution ; Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Teaching medical students about the impacts of climate change on human health

Jason Gomez / Anna Goshua / Nicholas Pokrajac / Barbara Erny / Paul Auerbach / Kari Nadeau / Michael A. Gisondi

The Journal of Climate Change and Health, Vol 3, Iss , Pp 100020- (2021)

2021

Abstract: Climate change is among the greatest threats to human health, yet most medical schools fail to adequately teach students about its impact. To address this educational gap, we designed and implemented a new elective course for Stanford medical students, “ ... ...

Abstract	Climate change is among the greatest threats to human health, yet most medical schools fail to adequately teach students about its impact. To address this educational gap, we designed and implemented a new elective course for Stanford medical students, “The Impact of Climate Change on Human Health.” Students (40/74, 54% response rate) evaluated its effectiveness by completing a pre/post-course survey that measured changes in their beliefs, attitudes, and knowledge about the health effects of climate change. We found significant increases in students' beliefs about the need for climate change education and related physician responsibilities. Intentions to change personal behaviors and apply new knowledge in future clinical practice also significantly increased. Our findings illustrate the importance of a medical school course on climate science and health. Additionally, we describe the curriculum design and program evaluation of our course.
Keywords	Climate change ; Medical education ; Climate health ; Public aspects of medicine ; RA1-1270 ; Meteorology. Climatology ; QC851-999
Subject code	796
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Homologies between SARS-CoV-2 and allergen proteins may direct T cell-mediated heterologous immune responses

Kathrin Balz / Abhinav Kaushik / Meng Chen / Franz Cemic / Vanessa Heger / Harald Renz / Kari Nadeau / Chrysanthi Skevaki

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 7

Abstract: Abstract The outbreak of the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a public health emergency. Asthma does not represent a risk factor for COVID-19 in several published cohorts. We hypothesized that the SARS-CoV-2 proteome ... ...

Abstract	Abstract The outbreak of the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a public health emergency. Asthma does not represent a risk factor for COVID-19 in several published cohorts. We hypothesized that the SARS-CoV-2 proteome contains T cell epitopes, which are potentially cross-reactive to allergen epitopes. We aimed at identifying homologous peptide sequences by means of two distinct complementary bioinformatics approaches. Pipeline 1 included prediction of MHC Class I and Class II epitopes contained in the SARS-CoV-2 proteome and allergens along with alignment and elaborate ranking approaches. Pipeline 2 involved alignment of SARS-CoV-2 overlapping peptides with known allergen-derived T cell epitopes. Our results indicate a large number of MHC Class I epitope pairs including known as well as de novo predicted allergen T cell epitopes with high probability for cross-reactivity. Allergen sources, such as Aspergillus fumigatus, Phleum pratense and Dermatophagoides species are of particular interest due to their association with multiple cross-reactive candidate peptides, independently of the applied bioinformatic approach. In contrast, peptides derived from food allergens, as well as MHC class II epitopes did not achieve high in silico ranking and were therefore not further investigated. Our findings warrant further experimental confirmation along with examination of the functional importance of such cross-reactive responses.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Correction

Mary Prunicki / Nicholas Cauwenberghs / Jennifer Arthur Ataam / Hesam Movassagh / Juyong Brian Kim / Tatiana Kuznetsova / Joseph C. Wu / Holden Maecker / Francois Haddad / Kari Nadeau

Environmental Health, Vol 21, Iss 1, Pp 1-

Immune biomarkers link air pollution exposure to blood pressure in adolescents

2022 Volume 4

Keywords	Industrial medicine. Industrial hygiene ; RC963-969 ; Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Infant infections, respiratory symptoms, and allergy in relation to timing of rice cereal introduction in a United States cohort

Yuka Moroishi / Antonio J. Signes-Pastor / Zhigang Li / Kathryn L. Cottingham / Brian P. Jackson / Tracy Punshon / Juliette Madan / Kari Nadeau / Jiang Gui / Margaret R. Karagas

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 8

Abstract: Abstract Rice products marketed in the USA, including baby rice cereal, contain inorganic arsenic, a putative immunotoxin. We sought to determine whether the timing of introduction of rice cereal in the first year of life influences occurrence of ... ...

Abstract	Abstract Rice products marketed in the USA, including baby rice cereal, contain inorganic arsenic, a putative immunotoxin. We sought to determine whether the timing of introduction of rice cereal in the first year of life influences occurrence of infections, respiratory symptoms, and allergy. Among 572 infants from the New Hampshire Birth Cohort Study, we used generalized estimating equation, adjusted for maternal smoking during pregnancy, marital status, education attainment, pre-pregnancy body mass index, maternal age at enrollment, infant birth weight, and breastfeeding history. Among 572 infants, each month earlier of introduction to rice cereal was associated with increased risks of subsequent upper respiratory tract infections (relative risk, RR = 1.04; 95% CI: 1.00–1.09); lower respiratory tract infections (RR = 1.19; 95% CI: 1.02–1.39); acute respiratory symptoms including wheeze, difficulty breathing, and cough (RR = 1.10; 95% CI: 1.00–1.22); fever requiring a prescription medicine (RR = 1.22; 95% CI: 1.02–1.45) and allergy diagnosed by a physician (RR = 1.20; 95% CI: 1.06–1.36). No clear associations were observed with gastrointestinal symptoms. Our findings suggest that introduction of rice cereal earlier may influence infants’ susceptibility to respiratory infections and allergy.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Immune biomarkers link air pollution exposure to blood pressure in adolescents

Mary Prunicki / Nicholas Cauwenberghs / Jennifer Arthur Ataam / Hesam Movassagh / Juyong Brian Kim / Tatiana Kuznetsova / Joseph C. Wu / Holden Maecker / Francois Haddad / Kari Nadeau

Environmental Health, Vol 19, Iss 1, Pp 1-

2020 Volume 17

Abstract: Abstract Background Childhood exposure to air pollution contributes to cardiovascular disease in adulthood. Immune and oxidative stress disturbances might mediate the effects of air pollution on the cardiovascular system, but the underlying mechanisms ... ...

Abstract	Abstract Background Childhood exposure to air pollution contributes to cardiovascular disease in adulthood. Immune and oxidative stress disturbances might mediate the effects of air pollution on the cardiovascular system, but the underlying mechanisms are poorly understood in adolescents. Therefore, we aimed to identify immune biomarkers linking air pollution exposure and blood pressure levels in adolescents. Methods We randomly recruited 100 adolescents (mean age, 16 years) from Fresno, California. Using central-site data, spatial-temporal modeling, and distance weighting exposures to the participant’s home, we estimated average pollutant levels [particulate matter (PM), polyaromatic hydrocarbons (PAH), ozone (O3), carbon monoxide (CO) and nitrogen oxides (NOx)]. We collected blood samples and vital signs on health visits. Using proteomic platforms, we quantitated markers of inflammation, oxidative stress, coagulation, and endothelial function. Immune cellular characterization was performed via mass cytometry (CyTOF). We investigated associations between pollutant levels, cytokines, immune cell types, and blood pressure (BP) using partial least squares (PLS) and linear regression, while adjusting for important confounders. Results Using PLS, biomarkers explaining most of the variance in air pollution exposure included markers of oxidative stress (GDF-15 and myeloperoxidase), acute inflammation (C-reactive protein), hemostasis (ADAMTS, D-dimer) and immune cell types such as monocytes. Most of these biomarkers were independently associated with the air pollution levels in fully adjusted regression models. In CyTOF analyses, monocytes were enriched in participants with the highest versus the lowest PM2.5 exposure. In both PLS and linear regression, diastolic BP was independently associated with PM2.5, NO, NO2, CO and PAH456 pollution levels (P ≤ 0.009). Moreover, monocyte levels were independently related to both air pollution and diastolic BP levels (P ≤ 0.010). In in vitro cell assays, plasma of participants ...
Keywords	Adolescent ; Blood pressure ; Immune ; Inflammation ; Air pollution ; Cardiovascular disease ; Industrial medicine. Industrial hygiene ; RC963-969 ; Public aspects of medicine ; RA1-1270
Subject code	333
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: High-dimensional profiling clusters asthma severity by lymphoid and non-lymphoid status

Matthew J. Camiolo / Xiaoying Zhou / Timothy B. Oriss / Qi Yan / Michael Gorry / William Horne / John B. Trudeau / Kathryn Scholl / Wei Chen / Jay K. Kolls / Prabir Ray / Florian J. Weisel / Nadine M. Weisel / Nima Aghaeepour / Kari Nadeau / Sally E. Wenzel / Anuradha Ray

Cell Reports, Vol 35, Iss 2, Pp 108974- (2021)

2021

Abstract: Summary: Clinical definitions of asthma fail to capture the heterogeneity of immune dysfunction in severe, treatment-refractory disease. Applying mass cytometry and machine learning to bronchoalveolar lavage (BAL) cells, we find that corticosteroid- ... ...

Abstract	Summary: Clinical definitions of asthma fail to capture the heterogeneity of immune dysfunction in severe, treatment-refractory disease. Applying mass cytometry and machine learning to bronchoalveolar lavage (BAL) cells, we find that corticosteroid-resistant asthma patients cluster largely into two groups: one enriched in interleukin (IL)-4+ innate immune cells and another dominated by interferon (IFN)-γ+ T cells, including tissue-resident memory cells. In contrast, BAL cells of a healthier population are enriched in IL-10+ macrophages. To better understand cellular mediators of severe asthma, we developed the Immune Cell Linkage through Exploratory Matrices (ICLite) algorithm to perform deconvolution of bulk RNA sequencing of mixed-cell populations. Signatures of mitosis and IL-7 signaling in CD206−FcεRI+CD127+IL-4+ innate cells in one patient group, contrasting with adaptive immune response in T cells in the other, are preserved across technologies. Transcriptional signatures uncovered by ICLite identify T-cell-high and T-cell-poor severe asthma patients in an independent cohort, suggesting broad applicability of our findings.
Keywords	severe asthma ; BAL ; immune ; multi-omics ; CyTOF ; RNA-seq ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Deconvoluting complex correlates of COVID-19 severity with a multi-omic pandemic tracking strategy

Victoria N. Parikh / Alexander G. Ioannidis / David Jimenez-Morales / John E. Gorzynski / Hannah N. De Jong / Xiran Liu / Jonasel Roque / Victoria P. Cepeda-Espinoza / Kazutoyo Osoegawa / Chris Hughes / Shirley C. Sutton / Nathan Youlton / Ruchi Joshi / David Amar / Yosuke Tanigawa / Douglas Russo / Justin Wong / Jessie T. Lauzon / Jacob Edelson /

Daniel Mas Montserrat / Yongchan Kwon / Simone Rubinacci / Olivier Delaneau / Lorenzo Cappello / Jaehee Kim / Massa J. Shoura / Archana N. Raja / Nathaniel Watson / Nathan Hammond / Elizabeth Spiteri / Kalyan C. Mallempati / Gonzalo Montero-Martín / Jeffrey Christle / Jennifer Kim / Anna Kirillova / Kinya Seo / Yong Huang / Chunli Zhao / Sonia Moreno-Grau / Steven G. Hershman / Karen P. Dalton / Jimmy Zhen / Jack Kamm / Karan D. Bhatt / Alina Isakova / Maurizio Morri / Thanmayi Ranganath / Catherine A. Blish / Angela J. Rogers / Kari Nadeau

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 10

Abstract: There is a genetic component to the risk of severe COVID-19, but the genetic effects are difficult to separate from social constructs that covary with genetic ancestry. To address this, the authors identify determinants of COVID-19 severity using ... ...

Abstract	There is a genetic component to the risk of severe COVID-19, but the genetic effects are difficult to separate from social constructs that covary with genetic ancestry. To address this, the authors identify determinants of COVID-19 severity using admixture mapping, viral phylodynamics, and host immune and metagenomic sequencing.
Keywords	Science ; Q
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Phase 2 Randomized Controlled Multisite Study Using Omalizumab-facilitated Rapid Desensitization to Test Continued vs Discontinued Dosing in Multifood Allergic Individuals

Sandra Andorf / Natasha Purington / Divya Kumar / Andrew Long / Katherine L. O'Laughlin / Scott Sicherer / Hugh Sampson / Antonella Cianferoni / Terri Brown Whitehorn / Daniel Petroni / Melanie Makhija / Rachel G. Robison / Michelle Lierl / Stephanie Logsdon / Manisha Desai / Stephen J. Galli / Efren Rael / Amal Assa'ad / Sharon Chinthrajah /

Jacqueline Pongracic / Jonathan M. Spergel / Jonathan Tam / Stephen Tilles / Julie Wang / Kari Nadeau

EClinicalMedicine, Vol 7, Iss , Pp 27-

2019 Volume 38

Abstract: Background: As there is limited data on the sustainability of desensitization of multifood-oral immunotherapy (multifood-OIT), we conducted a multisite multifood-OIT study to compare the efficacy of successful desensitization with sustained dosing vs ... ...

Abstract	Background: As there is limited data on the sustainability of desensitization of multifood-oral immunotherapy (multifood-OIT), we conducted a multisite multifood-OIT study to compare the efficacy of successful desensitization with sustained dosing vs discontinued dosing after multifood-OIT. Methods: We enrolled 70 participants, aged 5–22 years with multiple food allergies confirmed by double-blind placebo-controlled food challenges (DBPCFCs). In the open-label phase of the study, all participants received omalizumab (weeks 1–16) and multi-OIT (2–5 allergens; weeks 8–30) and eligible participants (on maintenance dose of each allergen by weeks 28–29) were randomized 1:1:1 to 1 g, 300 mg, or 0 mg arms (blinded, weeks 30–36) and then tested by food challenge at week 36. Success was defined as passing 2 g food challenge to at least 2 foods in week 36. Findings: Most participants were able to reach a dose of 2 g or higher of each of 2, 3, 4, and 5 food allergens (as applicable to the participant's food allergens in OIT) in week 36 food challenges. Using an intent-to-treat analysis, we did not find evidence that a 300 mg dose was effectively different than a 1 g dose in maintaining desensitization, and both together were more effective than OIT discontinuation (0 mg dose) (85% vs 55%, P = 0.03). Fifty-five percent of the intent-to-treat participants and 69% of per protocol participants randomized to the 0 mg arm showed no objective reactivity after 6 weeks of discontinuation. Cross-desensitization was found between cashew/pistachio and walnut/pecan when only one of the foods was part of OIT. No statistically significant safety differences were found between the three arms. Interpretation: These results suggest that sustained desensitization after omalizumab-facilitated multi-OIT best occurs through continued maintenance OIT dosing of either 300 mg or 1 g of each food allergen as opposed to discontinuation of multi-OIT. Funding: Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Jeff and ...
Keywords	Medicine (General) ; R5-920
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Eotaxin and FGF enhance signaling through an Extracellular signal-related kinase (ERK)-dependent pathway in the pathogenesis of Eosinophilic Esophagitis

Huang Jennifer J / Joh Jae / Fuentebella Judy / Patel Anup / Nguyen Tammie / Seki Scott / Hoyte Lisa / Reshamwala Neha / Nguyen Christine / Quiros Anthony / Bass Dorsey / Sibley Eric / Berquist William / Cox Kenneth / Kerner John / Kari Nadeau C

Allergy, Asthma & Clinical Immunology, Vol 6, Iss 1, p

2010 Volume 25

Abstract: Abstract Background Eosinophilic esophagitis (EoE) is characterized by the inflammation of the esophagus and the infiltration of eosinophils into the esophagus, leading to symptoms such as dysphagia and stricture formation. Systemic immune indicators ... ...

Abstract	Abstract Background Eosinophilic esophagitis (EoE) is characterized by the inflammation of the esophagus and the infiltration of eosinophils into the esophagus, leading to symptoms such as dysphagia and stricture formation. Systemic immune indicators like eotaxin and fibroblast growth factor were evaluated for possible synergistic pathological effects. Moreover, blood cells, local tissue, and plasma from EoE and control subjects were studied to determine if the localized disease was associated with a systemic effect that correlated with presence of EoE disease. Method Real-time polymerase chain reaction from peripheral blood mononuclear cells (PBMC), immunohistochemistry from local esophageal biopsies, fluid assays on plasma, and fluorescence-activated cell sorting on peripheral blood cells from subjects were used to study the systemic immune indicators in newly diagnosed EoE (n = 35), treated EoE (n = 9), Gastroesophageal reflux disease (GERD) (n = 8), ulcerative colitis (n = 5), Crohn's disease (n = 5), and healthy controls (n = 8). Result Of the transcripts tested for possible immune indicators, we found extracellular signal-regulated kinase (ERK), Bcl-2, bFGF (basic fibroblast growth factor), and eotaxin levels were highly upregulated in PBMC and associated with disease presence of EoE. Increased FGF detected by immunohistochemistry in esophageal tissues and in PBMC was correlated with low levels of pro-apoptotic factors (Fas, Caspase 8) in PBMC from EoE subjects. Plasma-derived bFGF was shown to be the most elevated and most specific in EoE subjects in comparison to healthy controls and disease control subjects. Conclusion We describe for the first time a possible mechanism by which increased FGF is associated with inhibiting apoptosis in local esophageal tissues of EoE subjects as compared to controls. Eotaxin and FGF signaling pathways share activation through the ERK pathway; together, they could act to increase eosinophil activation and prolong the half-life of eosinophils in local tissues of the esophagus in EoE subjects.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Allergy and Immunology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610
Language	English
Publishing date	2010-09-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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