bluuebunny/crossref_metadata_2025_split huggingface dataset:
LOFAR Detection of Post-starburst Galaxies
Authors: Mullick Riya , Omar Amitesh 
Published: August 2023

Abstract
We report detection of 104 radio counterparts in a sample of 1204 Sloan Digital Sky Survey-detected post-starburst (PSB) galaxies using the 144 MHz LOw-Frequency ARray (LOFAR) Two-meter Sky Survey Data Release 2 (LoTSS2). The detection rate of optically selected PSB galaxies in the 144 MHz images is ∼8.6% while that in the 1.4 GHz was estimated to be ∼1.8% using the Very Large Array-Faint Images of the Radio Sky at Twenty centimeter images. Although the 144 MHz radio luminosity shows no significant correlation with luminosity at other wave bands from optical to far-infrared, the fraction of radio-detected PSB galaxies shows a clear trend with absolute magnitude and colors in optical and Wide-field Infrared Survey Explorer infrared bands. A preliminary analysis suggests that the radio emission is dominated by Active Galactic Nuclei.
Exploring Novice Nurses' Experiences During the First Wave of the COVID-19 Pandemic
Authors: Pagnotta Ariana , Antonacci Rosetta , Curiale Lianna , Sanzone Lia , Kapoustina Oxana , Cervantes Amanda , Monaco Emma , Tsimicalis Argerie 
Published: August 2023

Background:
The coronavirus disease 2019 (COVID-19) pandemic affected how nurses learn and prepare for their future careers. This study explored the experiences of college-prepared, novice nurses pursuing a baccalaureate degree during the first wave of the pandemic.

Method:
This qualitative descriptive study analyzed students' individual reflective assignments describing the effects of the COVID-19 pandemic on novice nurses' personal, professional, and educational lives.

Results:
Three themes emerged: (1) emotions generated in the clinical workplace due to the lack of control and the unknown of working as novice nurses during a pandemic; (2) cognitive dissonance of the nursing role regarding novice nurses' moral distress and their growing empowerment within the scope of practice; and (3) a disconcerted image of nursing with contrasting views of nursing from the public's perspective and a disconnect between frontline workers and decision makers.

Conclusion:

Novel pedagogical strategies are needed to help novice nurses cope with stress, uncertainty, and role challenges to foster healthy learning in academic and working environments.

[
J Nurs Educ
. 2023;62(8):461–466.]
A novel self-adjuvanted mRNA vaccine expressing the Antigen-85B-p25 epitope of Mycobacterium tuberculosis protects mice against tuberculosis
Authors: Mishra Abhishek , Singh Vipul , Court Karem Pinto , Godin Biana , Sukhovershin Roman , Kiss Daniel , Khan Arshad , Jagannath Chinnaswamy 
Published: August 2023

Abstract
Mycobacterium tuberculosis (Mtb) is a leading cause of death due to infections. BCG is the most used vaccine despite having partial efficacy against the tuberculosis. We have developed a synthetic mRNA vaccine, SelmRp25-C5, which expresses the p25 epitope of Mtb-derived Antigen-85B and a TLR-2 stimulating C5 adjuvant peptide from CFP-10 protein. We evaluated its efficacy both ex vivo and in mice.

Methods
Mouse and human macrophages (MΦ) and mouse dendritic cells (DCs) were treated with SelmRp25-C5 vaccine or EGFP-mRNA control followed by antigen presentation assays and assessment of cytokine secretion. C57Bl/6 mice were vaccinated subcutaneously with two doses (5μg per mouse) of SelmRp25-C5 vaccine, or EGFP-mRNA and one dose of subcutaneous BCG (106 CFU per mouse) as a control, followed by aerosol infection with Mtb. Four weeks after Mtb challenge, mice were sacrificed, and organs were analyzed for Mtb CFU, RNAseq, Ag85B-p25 tetramer-specific CD4 T cells and memory T cells.

Results
SelmRp25-C5 vaccine induced robust antigen presentation to T cells in both mouse MΦs and DCs and in human MΦs, and enhanced Th1 cytokine secretion. Two doses of SelmRp25-C5 vaccine protected mice by reducing Mtb burden by 1log10. Protection induced by SelmRp25-C5 vaccine was associated with an increase in Ag85B-p25-specific CD4 T cells, increased IFN-γ and IL-2 secreting T cells and CD4 effector memory T cells. Lung and spleens of protected mice showed an upregulation of Spleen tyrosine kinase (Syk) and genes of the C-type lectin receptor-pathway compared to control mice.

Conclusions
We propose that the new generation self-adjuvanted mRNA vaccine strengthen both innate and adaptive immunity to provide protection against tuberculosis.

Supported by NIAID, NIH AI122070, AI138587; AI161015.
Structure-guided vaccine design to focus antibody responses to neutralizing epitopes on dengue virus envelope protein
Authors: Thiono Devina J , Samaras Demetrios , Phan Thanh T N , Tian Shaomin , Forsberg Lawrence J , Kuhlman Brian , de Silva Aravinda 
Published: August 2023

Abstract
The four dengue virus (DV) serotypes are mosquito-borne flaviviruses responsible for dengue fever. Live-attenuated DV vaccines that are in human trials have had mixed results with efficacy for just one or two serotypes and an increased dengue risk in some vaccinated populations. DV recombinant envelope (E) proteins as subunit vaccines have had limited success, likely due to DV wild type E protein (WT rE) is mostly monomeric at physiological temperature. Hence, it loses the quaternary structure epitopes recognized by neutralizing human antibodies (Ab) on the native dimer. We previously showed that with targeted amino acid mutations, we can form DV thermostable dimers (SD rE) displaying native quaternary epitopes targeted by strongly neutralizing Ab. Here we report on studies to test if Ab response can be directed to these quaternary epitopes by using SD rE as vaccine antigens. Since fusion loop (FL) Ab can cause antibody dependent enhancement (ADE) that increases disease severity upon heterologous DV infection, we also tested SD rE with mutated FL. Mice were immunized with DV2 WT rE or SD rE variants to compare Ab properties induced by each antigen. We found that SD-vaccinated mice had higher DV2 functional Ab titer compared to WT-vaccinated. To map vaccine responses, we run neutralization assays with chimeric epitope transplant DV and sera depleted of Ab subpopulations. We use ADE assay to determine if stabilized E dimer and mutated FL reduces ADE compared to WT rE. Preliminary results indicate that WT-vaccinated mice neutralizing Ab bind to simple epitopes on rE monomers, while SD-vaccinated mice had mostly dimer-specific neutralizing Ab. Our results demonstrate the promise of structure-guided design for developing dengue subunit vaccines.
NIH/NIAID U19 AI109784
R01AI107731
DOD/US Army Medical Research ACQ W81XWH1820034
Pre-existing T cell immune response specific to computationally optimized broadly reactive hemagglutinin antigens (COBRA-HA) in influenza vaccinees
Authors: Moraes Vanessa S , Souquette Aisha , Ross Ted M 
Published: August 2023

Abstract
The biggest challenge in developing a universal influenza vaccine is the extensive antigenic drift. In contrast to humoral immunity, cell-mediated immunity is more cross-reactive and can protect against various subtypes and drift variants. Our research group has described computationally optimized broadly reactive antigens (COBRA) to develop HA-based broadly protective influenza vaccine. However, studies that characterize the potential of COBRA-HA to elicit a functional T-cell response have yet to be developed. Cross-reactive response to conserved T cell epitopes from previous exposure can provide an efficient heterologous immunity. Thus, we aim to immune profile the pre-existing and cross-reactive COBRA-HA T cell response at the functionality and epitope conservation level to identify potential targets to be included in universal flu vaccine design. To achieve this goal, 50 donors who received the seasonal influenza vaccine (Fluzone, Sanofi) for two consecutive seasons were HLA typed, and the epitopes of COBRA-HA vaccine candidates Y2 (H1) and NG2 (H3) were predicted using IEDB software. Using the high dimensional flow cytometry, eight peptides for Y2 and 15 for NG2 were combined in pools to determine the phenotypes and cytokine secretion. We found that the vaccination induced a cross-reactive COBRA HA-specific CD4+ and CD8+ T cell response independent of antibody titers. Next, we will evaluate the Th helper subsets (Th1/Th2/Th17/cTfh) and the breadth of immune response by deconvoluting the pools in IFNγ Fluospot assay. Nonetheless, the next generation of the universal influenza vaccine recalled a functional CD4+ pre-existing response, demonstrating the potential efficacy of COBRA-HA in clinical trials.
National Institute of Allergy and Infectious Diseases (NIAID), U.S. National Institutes of Health (NIH), Department of Health and Human Services contract 75N93019C00052 (TMR).
Characterization of immune response towards modified Coxsackie B virus-like particle vaccine in a murine model
Authors: Soppela Saana Marika , González-Rodríguez Martin , Stone Virginia , Kummola Laura , Lampinen Vili , Jouppila Niila , Laitinen Olli , Flodström-Tullberg Malin , Junttila Ilkka , Hankaniemi Minna 
Published: August 2023

Abstract
Coxsackievirus Bs (CVBs) are common human RNA viruses that belong to the enterovirus genus of Picornaviridae. Most commonly, infections with these viruses manifest with mild flu-like symptoms. However, CVBs are also known to cause severe diseases, including aseptic meningitis, myocarditis, and chronic dilated cardiomyopathy (DCM), encephalitis, pancreatitis, and hand-foot-and-mouth disease. In this study, we aimed for a versatile characterization of a modified CVB virus-like particle vaccine in a murine model. The modified CVB-VLP was produced using baculovirus-insect cell production platform. Purified and characterized vaccine was administered to mice via s.c. or i.m. routes, either with or without an adjuvant. Immunological characterization of vaccine response included both humoral and cellular characterization. Antigen-specific IgG levels and neutralizing antibodies in the sera were measured to determine the humoral immune response. To characterize the cellular immunity, activation markers of the lymphocytes were identified using flow cytometry. Additionally, the cytokine secretion of the stimulated splenocytes was determined with FluoroSpot assay. The modified CVB-VLP induced high levels of IgG and neutralizing antibodies in the sera of vaccinated mice. Further, the in vitro stimulation of splenocytes induced activation of mainly CD4+ T-cells, and adjuvanted vaccine induced a significant production level of IFN-γ and IL-2. These results indicate that the virus-like particle combined with an adjuvant is a promising vaccine candidate. In addition, our current challenge study with coxsackie B1 virus will shed us more insight on the protective role of this vaccine.
Supported by grants from Finnish Foundations (Instrumentarium Science Foundation, Paulo Foundation and Ida Montini Foundation)
Immunogenicity of intravenous irradiated or auxotrophic BCG immunization in macaques
Authors: Robertson Molly A , Lehman Chelsea C , Buscan Allison N , Dahlvang James D , Darrah Patricia A , Roederer Mario , Seder Robert A 
Published: August 2023

Abstract
Tuberculosis (TB), caused by the bacillus Mycobacterium tuberculosis (Mtb), is a leading cause of death worldwide, particularly in people with HIV. The current vaccine against TB, BCG, is a live-attenuated strain of M. bovis that is administered intradermally at birth in endemic countries. BCG protects children against disseminated TB but fails to protect adolescents and adults against pulmonary TB, the most transmissible form. Thus, more effective TB vaccines are urgently needed. We previously demonstrated that delivering BCG intravenously (IV) elicits a high number of Mtb-specific T cells in the airway, the site of infection, and confers robust protection against Mtb challenge 6 months later in rhesus macaques. While whole organism vaccines provide broad antigenic breadth, safety concerns may limit clinical development of a replication-competent IV BCG regimen, especially in immunocompromised individuals. To address this, we vaccinated macaques IV with either irradiation-inactivated (Ird) BCG or a live, replication-incompetent auxotroph (Aux) of BCG and compared their immunogenicity in the bronchoalveolar lavage (BAL) to wild type (WT) BCG. Early results indicate that Aux BCG elicits a similar magnitude of Mtb-specific T cell responses in the BAL compared to WT BCG; in contrast, Ird BCG is less potent in generating such responses. These studies provide data on whether whole organism vaccines need to be live, persist, or replicate to confer durable immunity against TB.
Funded by the NIH Intramural Program
Investigating tissue-resident memory T cell differentiation of CAR T cells reveals an unexpected role for CD69
Authors: Cheng Menglin , Bergsbaken Tessa 
Published: August 2023

Abstract
Adoptive cell therapy using chimeric antigen receptor-expressing (CAR) CD8+ T cells has revolutionized the treatment of liquid tumors; however, CAR T cells have had more limited success against solid tumors. CD8+ tissue-resident memory T cells (Trm), which are characterized by surface expression of CD69 and CD103 and a unique transcription factor circuit, are found within solid tumors and associated with improved tumor control. However, it is unclear whether CAR T cells adopt Trm features in the tumor microenvironment and how enhancing Trm differentiation of CAR T cells might impact their efficacy against solid tumors. Using the murine tumor model MC38, we identified both CD69+CD103- and CD69+CD103+ subsets that express Trm signature genes. To examine if CAR T cells follow a similar differentiation pattern, human carcinoembryonic antigen (hCEA)-specific CAR T cells with either a CD28 or 4-1BB costimulatory domain were transferred into hosts bearing MC38-hCEA tumors. We found the CD28 domain drove expansion of the CAR T population while delaying Trm marker expression compared to 4-1BB and non-CAR T cells. The persistence of a CD69-CD103-subset of CD28 CAR T cells strongly correlated with the number of hCEA-CD28 CAR T cells within the tumor. CD69-CD103- hCEA-CD28 CAR T cells were more proliferative and expressed lower levels of surface markers associated with dysfunction, including PD-1 and LAG3. We hypothesized CD69 could negatively regulate T cell proliferation and function; indeed, deletion of CD69 in hCEA-CD28 CAR T cells enhanced their proliferation and accumulation within tumors. In summary, hCEA-CD28 CAR signaling delayed Trm differentiation and CD69 expression in solid tumors resulting in prolonged T cell proliferation.
NIH 7R01AI153096
TCR/Chimeric Antigen Receptor (CAR) Cross-Antagonism to Fine-Tune CAR-T cell Immunotherapy
Authors: Altan-Bonnet Grégoire , Kondo Taisuke , Bourassa François X , Achar Sooraj , DuSold Justyn , Cespedes Pablo , Wahlsten Madison , Gaud Guillaume , Love Paul E , Dustin Mike , François Paul , Taylor Naomi 
Published: August 2023

Abstract
Chimeric antigen receptor (CAR) T cells, are created by extracting T cells from a cancer patient, engineering them to express a CAR targeting a tumor specific molecule, then reintroducing them back into the patient. A patient’s T cells contain their own endogenous T cell receptors (TCRs) however, which could potentially interact with the exogenous CAR inserted into the cell. In this study, we examine how TCR and CAR signals interact upon CAR-T activation. We show that weak TCR stimulation can reduce (antagonize) or increase overall CAR-T response, both in vitro and in vivo, across multiple tumor models, in both mouse and human T cells. We further show that the behavior of these TCR/CAR interactions can be manipulated by changing various characteristics of the TCR, CAR, and associated ligands. While this behavior is complex, we show that it can be described by a single mathematical model based on the adaptive kinetic proofreading scheme of ligand discrimination. We conclude by presenting potential applications for cancer immunotherapy.
Intramural Research Program of the National Cancer Institute
IL-33 promotes cardiovascular lesions development in a mouse model of Kawasaki Disease
Authors: de Carvalho Thacyana Teixeira , Jena Prasant Kumar , Franklin Michael Kyle , Fishbein Michael C , Crother Timothy R , Chen Shuang , Shimada Kenichi , Arditi Moshe , Rivas Magali Noval 
Published: August 2023

Abstract
Kawasaki Disease (KD), a pediatric acute febrile illness and systemic vasculitis, is the leading cause of acquired heart diseases in children. Coronary artery aneurysms (CAAs) occur in up to 25% of untreated children, which is reduced to 5% with intravenous immunoglobulin (IVIG) treatment. However, up to 20% of KD patients are refractory to IVIG and at higher risk of CAAs, highlighting the need to characterize the mechanisms mediating KD vasculitis to develop more efficient therapies. IL-33 is released upon inflammation and tissue damage and exerts its effects by binding to its receptor ST2 (IL1RL1). Levels of IL-33 are elevated in KD patients during the acute phase. However, how IL-33 contributes to the development of KD cardiovascular lesions remains unknown. Using the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis, we observed increased Il33 mRNA expression in hearts and abdominal aortas aneurysms of LCWE-injected mice. While ST2 was detected by immunofluorescence in the abdominal aortas of both control and LCWE-injected mice, IL-33 was mainly detected in tissues from LCWE-injected mice. Single-cell RNA-sequencing of abdominal aortas from LCWE-injected mice indicated that Il33 transcripts were expressed primarily by fibroblasts, endothelial cells, B cells, and vascular smooth muscle cells. In contrast, Il1rl1 was highly expressed by tissue infiltrating regulatory T cells, macrophages, eosinophils, and neutrophils. Blocking IL-33 with either anti-IL-33 antibody or using Il33−/− mice significantly attenuated LCWE-induced KD vasculitis. Our results indicate that IL-33 promotes LCWE-induced KD vasculitis in mice and could therapeutically be targeted to inhibit KD cardiovascular lesions.
IL-17 Receptor A protects against Helicobacter pylori- induced gastric cancer
Authors: Algood Holly Marie Scott , Brackman Lee C , Dixon Beverly R E A , Bernard Margaret , Jung Matthew S , Joshi Nikhita , Green Emily H , Piazuelo M Blanca 
Published: August 2023

Abstract
Infection with Helicobacter pylori is the predominant risk factor for the development of gastric cancer. Risk is enhanced by specific H. pylori virulence factors, diet, and the inflammatory response. Chronic activation of T helper (Th) 1 and Th17 pathways contribute to inflammation. Previous work suggests that while IL-17 activates several antimicrobial components of the innate immune response, IL-17 is also required to prevent a hyper-inflammatory adaptive immune response. To investigate if IL-17 receptor signaling contributes to the development of carcinogenesis, the transgenic InsGAS mouse, which is susceptible to H. pylori-induced gastric cancer, was used. InsGAS mice and InsGAS Il17ra−/− mice were infected with a cag T4SS positive strain for up to 6 months. By 6 weeks post infection, IL-17RA deficiency led to increased bacterial burden and increased gastritis, concomitant with an exacerbated Th1/Th17 cytokine profile, increased B cell infiltration and enhanced production of IgA despite reduced Pigr expression. Paragastric lymph nodes of InsGAS Il17ra−/− mice, while enlarged relative to InsGAS mice, exhibited altered gene expression profiles and potential loss of fibroblastic reticular cells. Gastric pathologies, including intramucosal carcinoma and adenocarcinoma with submucosal invasion, developed more frequently by 3 and 6 months post infection in H. pylori-infected InsGASIl17ra−/− mice. These increases in severe gastric disease were accompanied by loss of parietal cells, loss of mucin-producing cells and enhanced expression of ceacam1. These data suggest that IL-17RA signaling activates a protective pathway to prevent excessive inflammation which can drive gastric carcinogenesis after H. pylori infection.
This work was supported in part by Merit Review I01BX000915 (Algood) from the U.S. Department of Veterans Affairs, Biomedical Laboratory Research and Development Service. We acknowledge the Translational Pathology Shared Resource supported by NCI.NIH Cancer Center Support Grant 5P30 CA68485-19. Core Services performed through Vanderbilt University Medical Center’s Digestive Disease Research Center supported by NIH grant P30DK058404.
Immunomodulators identified via high-throughput screening enhance control of vaccine adjuvanticity
Authors: Rosenberger Matthew Glenn , Kim Jeremiah , Esser-Kahn Aaron 
Published: August 2023

Abstract
Stimulation of the innate immune system is crucial in both vaccinations and immunotherapies. This is often achieved through adjuvants, molecules that usually activate pattern recognition receptors (PRRs) and stimulate two innate immune signaling pathways: the nuclear factor kappa-light-chain-enhancer of activated B-cells pathway (NF-κB) and the interferon regulatory factors pathway (IRF). Engineering the immune response via fine control of these pathways, however, is quite difficult. We demonstrate the ability to alter and improve adjuvant activity via the addition of small molecule “immunomodulators” to existing PRR agonists. By modulating signaling activity instead of receptor binding, these molecules allow the customization of select innate responses. We demonstrate both inhibition and enhancement of the products of the NF-κB and IRF pathways by several orders of magnitude. Some modulators apply generally across many receptors, while others focus specifically on individual receptors. Modulators boosted correlates of a protective immune responses in an inactivated flu vaccine and reduced correlates of reactogenicity in a subunit typhoid vaccine. These modulators have a range of applications: from adjuvanticity in prophylactics to enhancement of immunotherapy. This approach to adjuvanticity offers greater control over early immune activation and provides researchers with a new tool to tailor end immune responses.
NIH 75N93019C00041
Immunological consequences of CD91 Single Nucleotide Polymorphisms in patients with sarcomas
Authors: Sedlacek Abigail L , Binder Robert J 
Published: August 2023

Abstract
Tumor immunosurveillance is critically dependent on several immune cell types and proteins including CD91. CD91 is expressed on the surface of antigen presenting cells (APCs) and binds a select few heat shock proteins (HSPs) released by dying tumor cells. These HSPs carry tumor antigens and initiate anti-tumor immune responses in de novo tumors. We have previously shown among multiple sarcoma types, osteosarcomas are poorly infiltrated by T cells and poorly immune edited. This correlates with reduced expression of CD91 on the surface of intratumoral APCs. CD91 is a highly polymorphic gene within the human population. Over 3500 single nucleotide polymorphisms (SNPs) have been identified, despite the relatively high conservation of CD91 throughout evolution. We have identified 155 of these SNPs within our sarcoma patient population, 11 of which are exonic and non-synonymous. We analyzed the immunologic data we obtained from patients with non-synonymous SNPs to patients with normal CD91 protein sequences. In addition, we used the computational modeling programs SIFT and PolyPhen-2 to predict the effects of these mutations on CD91 protein folding. SNPs rs746886209 and rs758644665 were indicated by both SIFT and PolyPhen-2 to have deleterious effects on CD91 folding and patients with these mutations had below average immune infiltration. While these data are currently correlative, we have developed an in vitro model to obtain proof of concept.