bluuebunny/crossref_metadata_2025_split huggingface dataset:
Лексико-семантические особенности репрезентации лингвокультуры орфизма (на материале сопоставления отрывка текста пьесы У. Шекспира The Tempest / «Буря» и его русскоязычных переводов)
Authors: С.Н. Вековищева , М.С. Демин 
Published: November 2024

В работе анализируется лексико-семантическая репрезентация лингвокультуры орфизма в тексте пьесы У. Шекспира The Tempest / «Буря» и ее русскоязычных переводов. В статье на основе исследований, посвященных орфизму, дается определение данному понятию с позиции лингвистики. Для исследования данного полисемантического лингвокультурного комплекса рассматриваются лексические единицы, содержащие в себе контекстуальные семы. При помощи совокупности методов (направленной выборки, стилистической интерпретации текста, сравнительно-сопоставительного анализа, индуктивного и дедуктивного, интерпретации результатов) разработан алгоритм анализа лексических единиц с множественными семами. Исследуются их возможности непрямой номинации, системные отношения единиц при семантическом сдвиге в двуязычной языковой ситуации, что позволяет проанализировать модальность и хронотоп орфических текстов, а также связанные с ними переводческие трансформации. Полученные результаты позволяют интерпретировать орфические сюжеты в литературе с позиции семантики, лексикологии, лингвистики текста и переводоведения.
The present work studies the lexical and semantic representation of the linguoculture of orphism in the text of Shakespeare’s play The Tempest and its Russian-language translations. The paper, based on research on orphism, defines this concept from the perspective of linguistics. The study of this polysemantic linguistic and cultural phenomenon involves lexical units containing contextual semes. An algorithm for analyzing lexical units with multiple semes has been developed via using a set of methods (directional sampling, stylistic interpretation of the text, comparative analysis, inductive and deductive methods, interpretation of the results). Such aspects as the possibilities of indirect nomination, the systemic relations of the units with a semantic shift in a bilingual language situation allow us to analyze the modality and chronotope of orphic texts and the translation transformations associated with them. The obtained results make it possible to interpret orphic plots in literature from the perspective of semantics, lexicology, text linguistics and translation studies.
Les essais contrôlés randomisés au Royaume-Uni : évaluer les interventions efficaces pour favoriser l’apprentissage des mathématiques
Authors: Roques Nathalie 
Published: November 2024

Depuis sa création en 2011, Education Endowment Foudation (EEF) a réalisé une centaine d’essais contrôlés randomisés (ECR) dans les établissements scolaires britanniques. Il s’agit pour cette fondation d’évaluer de façon scientifique l’impact d’interventions ciblées sur les apprentissages des élèves et de permettre aux acteurs en charge de l’enseignement de définir les actions à mettre en œuvre afin d’élever le niveau scolaire. Les évaluations de l’impact d’une intervention d’une part et de sa mise en œuvre d’autre part, sont encadrées par des procédures clairement définies par EEF et s’appuient sur le cadre plus vaste des études par comparaison de groupes. Leurs études d’efficacité en conditions réelles montrent que les élèves ont progressé en mathématiques au mieux de 3 mois (ce qui correspond à une taille d’effet égale à 0,26). Enfin, d’après les conclusions d’une méta-analyse conduite sur 48 résultats en mathématiques, les élèves de milieux socio-économiques défavorisés n’ont pas plus profité de ces interventions que les autres élèves. L’intérêt porté à ce type d’analyse par le Conseil Scientifique de l’Éducation nationale (CSEN) souligne que ce pan de la recherche est probablement amené à prendre de l’importance en France dans le domaine des Sciences de l’Éducation.
Autoimmune CD4 T cell exhaustion is counteracted by peripheral circulating T cell population with stem-like potential
Authors: Aljobaily Nouf , Allard-Trout Denise , Raugh Arielle , Perkins Bryant , Kolawole Elizabeth , Liu Baoyu , Galland Tessa , Jing Yi , Stephens Zac , Evavold Brian , Hale Scott , Bettini Matthew , Bettini Maria 
Published: November 2024

Abstract
Stem-like antigen specific T cells serve as a reservoir for autoimmune CD8 T cell responses. However, it is unclear whether CD4 T cells depend on a similar population to counteract depletion through terminal differentiation and exhaustion. Single cell RNAseq and flow cytometric analysis of NOD islet-infiltrating T cells revealed the heterogeneity of CD4 cells, with subpopulations displaying features of exhaustion. Blockade of T cell entry with FTY720 reduced T cell numbers in the tissue, and protected NOD mice from diabetes. Moreover, islet CD4 T cells progressively lose TCF1 expression overtime. Transfer experiments and T cell tracking in photoconvertible NOD.KikGR mice showed peripheral circulating T cells with stem-like TCF1+ phenotype as an important source for autoimmune T cells. We observed that islet infiltrating CD62L+ naïve-like T cells include low affinity antigen specific cells, show activation of TCR regulated genes, and exhibit epigenetic signature distinct from lymph node bona fide naïve T cells. Similarly, BDC2.5 islet antigen specific T cells circulating in peripheral non-draining lymphoid organs exhibit phenotypic and epigenetic signature of pre-primed, but largely undifferentiated T cells. Collectively, our data indicates that autoimmune CD4 T cell persistence is sustained through continuous recruitment of new T cells from circulating non-differentiated stem-like compartment.
Activation of APOBEC3B in Self-Inactivating Lentiviral-Based CAR T Cell Production Increases the Mutational Load and Decreases the Killing Efficiency of CAR T Cells
Authors: Swanson Jack , Tonne Jason , Vile Richard 
Published: November 2024

Abstract
Apolipoprotein B mRNA editing enzyme, catalytic polypeptides (APOBECs) are a family of cytidine deaminase enzymes well described in anti-retroviral defense which convert cytidines to uracils (C-U), leading to C-T mutations in DNA. We investigated whether activation of APOBEC3B during the process of making chimeric antigen receptor (CAR) T cells via lentiviral vector affects the overall mutational integrity of resulting CAR T cells. To investigate this question, we quantified APOBEC3B expression and APOBEC signature mutations both post transfection in 293T viral producer cells and post transduction in human T cells. We observed abundant APOBEC3B activation and APOBEC3 signature mutations after transfection of plasmids to make lentivirus, but minimal APOBEC3B activation with a few additional APOBEC3 signature mutations after transduction. To test the functional relevance of APOBEC3B activity, we overexpressed APOBEC3B in 293T cells, and produced lentivirus from the 293T cells overexpressing APOBEC3B. The CAR T cells transduced with lentivirus from the 293T cells overexpressing APOBEC3B exhibited reduced killing ability compared to CAR T cells from 293T cells with no transgene. Taken together, these data suggest that APOBEC3B activation during the process of CAR T cell production induces mutations and reduces CAR T cell killing, and that selective ablation of APOBEC enzymes in GMP-grade lentiviral producer cells may enhance the overall quality of CAR T cells for clinical use.
Strategies for Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy in Remote Settings
Authors: Watson Jessica , Smith Natalie , Cohen Michael , Alipaz Julie , Loh Christina , King David , Fazekas de St Groth Barbara , McGuire Helen 
Published: November 2024

Abstract
Comprehensive immune monitoring of clinical trials relies on the ability to generate high-quality data to gain insights into disease detection and treatment. Execution of longitudinal clinical trials in flow cytometry is complex due to logistical challenges in high-quality sample collection. Our group has developed a novel blood “immune signature” of cancer nonresponsiveness that predicts failure to make a clinical response to checkpoint immunotherapies targeting the PD-1/PD-L1 pathway. Recent advances in CyTOF™ technology allow us to expand clinical implementation to remote settings with a 50-plus-marker panel. CyTOF is the only technology that allows remote asynchronous sample collection with the largest immunophenotyping panel yielding reproducible results. This approach is uniquely enabled using a stable lyophilized large-scale staining panel and achieving comprehensive marker coverage in one panel minimizes blood sample required. CyTOF enables a simplified workflow including blood collection and processing in remote locations to enable the simplest clinical trial infrastructure complexity and cost, easily implemented in current hospital labs. This study is designed to demonstrate the clinical impact and utility of CyTOF for a highly simplified workflow for multi-site clinical trials. We report on the first phase of this project that implements this simplified workflow across remote clinical collection sites, data integration, and analysis.
Persistent immune shifts: Unveiling the legacy of vasopressin-triggered preeclampsia in offspring
Authors: Bunton Olivia , Brummond Daniel , Mikkelsen Emma , Scroggins Douglas , Scroggins Sabrina 
Published: November 2024

Abstract
Preeclampsia (PreE), a hypertensive disorder in pregnancy, is the global leading cause of maternal-fetal morbidity and mortality. Previously, we noted immune cell changes at gestational day 18 (GD18) in offspring of PreE. While offspring cardiovascular and metabolic risks are increasingly studied, there is comparatively less investigation into the persistence of immune cell changes post-PreE in offspring. Our study aims to assess the persistence of immune cell changes observed in PreE-affected offspring on GD18 (term in mice) postnatally into adulthood. PreE was induced in virgin C57BL/6J female mice by infusion of vasopressin (AVP) or saline via subcutaneous infusion throughout gestation. Offspring were euthanized at postnatal week 1, 7, or 12 for experimental outcomes. Offspring body and heart weight were recorded, and total urine protein was quantified. Flow cytometry was used to evaluate immune cell populations. Total T cells, as well as CD4+ and CD8+ T cells, were increased in the offspring of PreE postnatally. Surprisingly, there was also an increase in total B cells and isotype-switched B cells, while macrophage populations were decreased in offspring from AVP-induced dams. Our results confirm that immune cell alterations triggered by PreE persist in offspring postnatally. Ongoing research focuses on unraveling the implications of these immune cell changes in potentially shaping responses to pathogens and the development of autoimmune diseases later in life.
Evaluation of cyclin D3 as a transcriptional regulator in a neutrophil differentiation model.
Authors: Powers Sarah , Horvath Kylie , Shamsi Aiysha , Banjo Rachel 
Published: November 2024

Abstract
Cyclin D3 is known to regulate cell cycle entry during the G1 to S transition by associating with its binding partners CDK4/6 upon mitogenic stimulation. Cyclin D3 has also been implicated as a transcriptional regulator, but the indirect mechanism employed is not known. The HL60 cell line was used as a model to investigate cyclin D3’s role in altered gene transcription as DMSO-driven differentiation into neutrophils is induced. We have validated this system by evaluating changes in gene expression indicative of progression to the terminal neutrophil state. Interestingly, ectopic expression of cyclin D3 in undifferentiated HL60 (uHL60) cells causes changes in gene expression to mirror that seen in differentiated (dHL60) cells without the need to treat with DMSO. We have also assessed a cohort of target genes hypothesized to be sensitive to cyclin D3-impacted gene transcription as cells transition from uHL60 to dHL60. For those genes that are differentially expressed between uHL60 and dHL60, many are also sensitive to ectopic expression of cyclin D3. Forced expression of cyclin D3 mutants in uHL60 cells suggests that a C-terminal domain within cyclin D3 is responsible for this observed regulation of gene expression, as three mutations (L215M, Q244R, P278R) abrogate the wild-type cyclin D3-induced differentiation gene signature. Ongoing studies aim to elucidate transcription factor binding partners that interact in complex with cyclin D3 to cause differential gene expression.
Trained Immunity Generated by The Recombinant Zoster Vaccine (RZV)
Authors: Johnson Michael , Crotteau Megan , Ghosh Debashis , Levin Myron , Weinberg Adriana 
Published: November 2024

Abstract
Development of trained immunity after vaccination is of growing interest. We studied innate immune responses to RZV, which is a highly efficacious adjuvanted recombinant glycoprotein E (rgE) zoster vaccine administered in 2 doses.
Blood mononuclear cells from 10 RZV recipients were stimulated with gE overlapping peptides, rgE or medium. B cell, monocyte and DC responses were measured by PDL1 expression and NK, γδ, and conventional T cell (Tconv) responses by CD25 and CD137 co-expression. Innate and Tconv responses had similar 2-phase kinetics with a transient increase post-dose 1 and persistent increase post-dose 2 for up to 1year. In 14 vaccinees, we verified that DC, NK and monocyte responses to rgE remained higher than pre-vaccination for up to 5 years. Innate and Tconv responses did not correlate with each other ruling out bystander activation. Purified monocytes and NK cells from 10 vaccinees (6 CMV-seropositive) stimulated with rgE, CMV lysate or medium showed increased responses to both rgE and CMV from pre to postvaccination indicating the development of homologous and heterologous trained immunity. Monocyte ATAC-seq analysis showed significant chromatin changes in 16 genes from pre to postvaccination, including decreased chromatin accessibility of the TGFβ pathway postvaccination, which may represent the mechanism underlying the development of trained immunity.
In conclusion, RZV generated robust and lasting trained immunity that may contribute to its high efficacy.
Longitudinal analysis of IAV-specific CD8+ T cell response to the high dose influenza vaccine (Fluzone) in healthy older adults
Authors: Elbahnasawy Mostafa , Lu Jain , Reed Quinton , Hemani Humza , Li Jiangyuan , Cifallo Jeffrey , Li Huifen , Wallace Tonya , Dunn Christopher , Nguyen Cuong , Ruffolo Jeannie , Zukley Linda , Shi Guixin , Fan Jinshui , Liu Yu-Tsueng , De Supriyo , Chia Chee 
Published: November 2024

Abstract
Influenza infection remains a leading cause of death among older adults worldwide. While vaccines offer an effective means of reducing the severity of influenza, their efficacy reduces in this demographic. To gain insight into the adaptive immune response, we conducted an analysis of antigen-specific CD8+ T cells before and after the administration of the high-dose seasonal influenza vaccine (Fluzone) over six seasons (2014, 2018, 2019, 2021, 2022, and 2023) in a cohort of healthy older adults (n=37, M=18, F=19, aged 72-92, spanning visits 1-3). Using the HAI assay, we observed seroconversion (a 4-fold antibody increase post-vaccination) for most strains (&gt;67% of strains) in 46% of donors, for less than half of the strains (25-50% of strains) in 13% of donors, and no seroconversion (0% of strains) occurred in 30% of donors. Notably, there was a twofold higher occurrence of seroconversion for Influenza A virus (IAV) (51%) compared to Influenza B virus (IBV) (25%). As age advanced, 54% of donors exhibited a reduced antibody response, while 23% either experienced no change or saw an increase in their antibody response. Presently, we investigate the frequency and clonotype of influenza A virus (IAV) M1158-166-specific CD8+ T cells, tracking their changes post-vaccination and over a span of 1-5 years. This endeavor aims to uncover new insights into the molecular basis of the reduced antigen-specific CD8+ T cell response observed in certain older adults.
Vaccinia viral-vector vaccine targeting outer surface protein C protects against Lyme disease in mice
Authors: Pfeifle Annabelle , Cao Jingxin , Zhang Wanyue , Thulasi Raman Sathya , Li Sean 
Published: November 2024

Abstract
Lyme disease (LD) is the most common vector-borne illness in North America. The annual incidence of LD has risen drastically over the past decade, nearing an estimated half a million cases last year. LD is caused by infection with the bacteria B. burgdorferi, which is transmitted by a tick vector. Currently, there is no vaccine available for the prevention of LD in humans, emphasizing the need for novel vaccine development strategies. In this study, we engineered a modified Vaccinia virus to express the outer surface protein C (OspC) of B. burgdorferi (VV-OspC). Six-week old C3H/HeN mice were prime and boost vaccinated intramuscularly with the VV-OspC vaccine one month prior to subcutaneous needle challenge with B. burgdorferi. The candidate vaccine was found to elicit high titres of OspC-specific antibodies with a Th1-bias that were capable of inducing phagocytosis of B. Burgdorferi in vitro. VV-OspC was also found to induce a balanced cell-mediated cytokine response in the spleen. Furthermore, qPCR analysis of the bacterial burden revealed that the candidate vaccine afforded complete protection against infection and bacterial dissemination two weeks post-challenge. Vaccinated mice were also protected against clinical signs of Lyme disease, including carditis and lymphadenopathy. Overall, the results of this study provide support for the use of a viral-vector vaccine platform for the development of LD vaccines.
Identifying Mtb-Specific T Cell Epitopes Across the Spectrum of Tuberculosis Infection: Implications for Diagnostics and Vaccines
Authors: Panda Sudhasini , Morgan Jeffrey , Cheng Catherine , Saito Mayuko , Gilman Robert , Ciobanu Nelly , Crudu Valeriu , Catanzaro Donald , Catanzaro Antonino , Rodwell Timothy , Perera Judy , Chathuranga Teshan , Gunasena Bandu , DeSilva Aruna , Peters Bjoern , Sette Alessandro , Arlehamn Cecilia S 
Published: November 2024

Abstract
The challenge in advancing tuberculosis (TB) diagnostics and vaccines arises from our limited understanding of diverse Mtb antigens triggering distinct T cell responses in spectrum of TB infection. We addressed this with a comprehensive analysis, screening 20,610 Mtb-derived T cell epitopes using IFNγ Fluorospot in active TB (ATB) and BCG-vaccinated individuals, comparing to LTBI. We identified 137 unique epitopes in ATB, 16% recognized by multiple participants, suggesting a broad response, mainly targeting cell wall and cell processes antigens. BCG-vaccinated individuals also showed a heterogeneous response with 85 unique epitopes. There was little overlap between the epitopes found in ATB and BCG-vaccinated individuals, implying distinct antigen recognition in spectrum of TB. From these findings, we developed an ATB-specific peptide pool (ATB116), distinguishing pulmonary ATB with over 60% sensitivity and 80% specificity across diverse locations. We also aligned the identified epitopes with 157 mycobacteria strains to assess their conservation across different Mtb strains and the broader mycobacterium genus. This revealed 17% of the epitopes are 100% conserved across the mycobacterium genus, suggesting that the sensitivity and specificity of the peptide pools can be improved. In summary, our T cell reactivity analysis identified stage-specific Mtb epitopes, offering diagnostic potential, measuring Mtb-specific immune responses, and advancing vaccine development.
FOXO1 inhibitor has the antiviral and anti-inflammatory effects against SARS-CoV-2 infection in in vitro and in vivo models.
Authors: Furukawa Ryutaro , Hara Atsushi , Ouji-Sageshima Noriko , Kitabatake Masahiro , Shichino Shigeyuki , Ueha Satoshi , Matsushima Kouji , Ito Toshihiro 
Published: November 2024

Abstract
COVID-19 treatment aims to inhibit SARS-CoV-2 replication and subsequent hyper-inflammatory responses. Forkhead box O1 (FOXO1) is a transcription factor involved in various physiological processes, including inflammation and immune systems. Here, we investigated the antiviral and anti-inflammatory effects of AS1842856 (AS), a FOXO1 inhibitor, against SARS-CoV-2 infection. We found that AS could suppress viral load and active virus titers in Calu-3, a human airway epithelial cell line, infected with SARS-CoV-2. In addition, the expression of inflammatory-related cytokines was reduced, while that of IL-10, an anti-inflammatory cytokine, was increased by AS. AS also reduced expressions of ACE2 and TMPRSS2, both host cell proteins required for SARS-CoV-2 infection. Moreover, we investigated the effects of AS in animal models. AS administration (50 mg/kg/day, i.p.) into a Syrian hamster model resulted in reduced weight loss, a decrease in viral load in lungs, and histological improvement of pneumonia. We also found AS improved survival rate in mouse COVID-19 models, generated by using mouse-adapted QHmusX strain. Single-cell RNA sequencing using hamster lungs indicated AS suppressed SARS-CoV-2 gene in alveolar epithelial cells and decreased CXCL10+ macrophages, which are related to pathogenesis of severe COVID-19 according to previous studies. Our results suggested AS could attenuate the severity of COVID-19 by modifying immune responses and suppressing SARS-CoV-2 infection.
Extent of immune history shapes the antibody response against the influenza virus in a mouse model
Authors: Lyu Huibin , LYU HUIBIN , Teo Qi Wen , Lee Chang-Chun , Liang Weiwen , Choi Danbi , Mao Kevin , Bruzzone Roberto , Wilson Ian , Wu Nicholas , Mok Chris 
Published: November 2024

Abstract
Antigenic imprinting refers to the effects of prior exposures on subsequent immune responses to antigenically related viral strains and the human immune history influences the magnitude and quality of future antibody responses. However, the impact of age-dependent immune history on the antibody response to the 2009 H1N1 virus remains largely elusive, primarily due to the complexity of human experiences with infection and vaccination. Moreover, how the extent of immune history affects antibody response is unclear. In this study, we investigated the antigenic imprinting effect on hemagglutinin (HA) and neuraminidase (NA) by utilizing a mouse model, sequentially infecting them with pre-2009 seasonal H1N1 viruses and challenging them with 2009 H1N1 virus. We assessed HA- and NA-specific antibodies both before and after subjecting different groups of mice to the 2009 H1N1 viral challenge. Intriguingly, our findings show that the extent of prior infection experience influences the functional antibody response to both HA and NA against antigenically drifted or shifted strains. Furthermore, our additional experiments revealed that the pattern of antigenic imprinting for HA and NA is different across different virus strains. In conclusion, this study underscores how the extent of prior infection experiences can determine the quality and specificity of antibody responses. These findings are vital for developing more effective strategies for vaccination and antiviral treatments.