bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of effective immunotherapy for triple negative breast cancer by WEE1 kinase inhibition
Authors: Choi Mi Ran , Xie Ping , Tang Hui , Fan Jie , Ahn Ji Hae , Orpano Rachel , Zhang Bin 
Published: August 2023

Abstract
Treatment options for triple negative breast cancer (TNBC) are limited because they are usually insensitive to most available hormonal or targeted therapeutic agents owing to their triple negative nature. Exciting clinical results using immune checkpoint inhibitors (ICI) directed against PD-1/PD-L1 have been reported. However, only a subset of patients (~20%) respond to ICI. Therefore, identifying rational combinations is needed to enhance the efficacy of immunotherapy in TNBC. We demonstrated there that inhibition of WEE1, a G2/M cell cycle checkpoint regulator induced by DNA damage, increased expression levels of MHC-I, and pro-inflammatory chemokines (CXCL9 and CXCL10) together with PD-L1 in human and mouse TNBC cells. Consequently, WEE1 inhibition enhanced cytotoxic T-lymphocyte (CTL)-mediated killing of tumor cells, and CTL infiltration into the tumor, making tumors susceptible to anti-PD-1 mAb immune checkpoint blockade in mouse TNBC models in a CD8+ T cell–dependent manner. Mechanistically, WEE1 inhibition triggered the cellular damage stress and interferon response through the double-stranded DNA/RNA (dsDNA/RNA) by activating the TLR9/IRF7 pathway. Furthermore, combining WEE1 inhibition and TLR9 agonist CpG DNA resulted in tumor regression, facilitating an effective antitumor T cell response. Our findings have rapid translational implications for the exploration of WEE1 inhibitors alongside agents that stimulate CD8+ T cell activity, including ICI and TLR9 agonists, which are both clinically available to treat TNBC patients.
We acknowledge the funding support from NCI R01CA222963 and DoD W81XWH-19-1-0106.
A novel tumor-bearing humanized mouse model for evaluating the efficacy and predictive safety of bispecific T cell engager
Authors: Yang Guoxiang , Yang Hongyuan , Ordones Evie , Yao Li-Chin , Yang Jiwon , Keck James G , Cheng Mingshan 
Published: August 2023

Abstract
Bispecific T cell engager (BiTE) is one of the most promising therapeutic approaches for treatment of various malignancies. Humanized mice engrafted with human peripheral blood mononuclear cells (PBMCs) have currently become the preclinical platform for evaluating the effectiveness of various cancer immunotherapies including BiTE. However, the wide application of this humanized animal model is limited by a strong xenoreaction of human T cells against the mouse tissues. In this study, we used humanized murine major histocompatibility class I and class II double knock-out NSG mice (referred to DKO) to evaluate the antitumor effect of BiTE. The DKO mice were implanted with human pre-B acute lymphoblastic leukemia cell line (Nalm6). Five days later, the mice were reconstituted with PBMCs. Following CD19xCD3 BiTE treatment whole-body tumor burden was quantified by a in vivo imaging system. Our data demonstrated that the mice developed consistent clinical signs of leukemia-related body weight loss and hind-limb paralysis within 4 weeks. With serial dose of CD19xCD3 BiTE treatment, the tumor cell growing was significantly suppressed. A lower incidence of hind-limb paralysis with prolonged survival were observed in BiTE-treated mice compared with controls. In addition, after treatment with CD19xCD3 BiTE, the humanized mice exhibited elevated serum levels of human IFN-γ, TNF-a, IL-6, IL-10, IL-2, and IL-4. The cytokine production was dose-dependent and associated with the increase of CD19xCD3 BiTE effectiveness. This tumor-bearing humanized model provides a promising preclinical platform for evaluating the efficacy, toxic cytokine release, and dosing requirements of any T cell-based immunotherapies for cancer treatment.
A case for teaching basic immunology through scientific journalism-lesson taught by a Coronavirus went viral!
Authors: Fazal Nadeem , Alsiyaghy Jassam , Eshetie Kirubel , Wilson Kiara D , Newaz Mohammad , Faridi Hafeez , Tauseef Mohammad , Graefen Bahar , Aliyeva Leyla , Najafova Nurana 
Published: August 2023

Abstract
Sudden switch to online mode of learning in the March of 2020 for a Basic Immunology course lead to a cascade of experimenting teaching strategies. We at College of Pharmacy Chicago State University experimented such innovative teaching techniques for two consecutive spring semesters. One such teaching method was to deliver course content material through use of mainstream media (MSM) via scientific journalism. Basic immunology course content was divided into media-inspired topics of public concern and the students were made to research and review selected topics before we discussed those in virtual classrooms. The most common topics included immunology terms (antigen, antibody, immune reaction, innate and adaptive immunity, immunology of infection, ARDS, non-pharmacological interventions (NPI) like lockdown, masking and herd immunity, development of vaccines and therapeutics of infectious diseases. The students researched those topics in daily news outlets, i.e., TV, Radio, Newspaper, Social media (YouTube, Facebook, Twitter, Instagram), and presented to the class the underlying and foundational immunology concepts making the breaking news. Subjective data was collected through student opinion surveys and objective data was analyzed through students’ performance, assessments, grades, and Course and Faculty evaluations. The study found a positive correlation between the use of scientific journalism as a teaching tool and students’ engagement, comprehension, retention and academic outcomes. The publications authored by Scientific Journalists presented the complex and complicated immunology material in a very simple and understandable way for the public, which complemented immunology students’ learning as well.
A Perfect Fit: 3D-Printed Kit to Teach Students Principles of Antigen-Antibody Recognition and Herd Immunity
Authors: Ohashi Sarah N , Hughes Lindsey D , Connolly Kelli , Wang Jennifer , Velazquez Sofia , Tabachnikova Sasha , Kavathas Paula 
Published: August 2023

Abstract
The immunological principles underlying vaccines are a critical part of understanding human health and disease, but are typically not included in general K-12 education curriculum. The COVID-19 pandemic has underscored both the power of science and the importance of science literacy for our country. Though multifactorial, vaccine hesitancy is associated with patients’ lack of information surrounding vaccine biology. Recognizing this gap, we aimed to develop innovative learning activities that would distill the complex concepts of adaptive immunity and herd immunity to make them accessible to middle and high school students.
Herein, we present one such learning activity intended to help students visualize the structural features of an antibody and the specificity of antibody-antigen interactions. Each student is provided with a base 3D-printed antibody, along with three sets of exchangeable variable domains and three model pathogens. Students explore the ability of their antibody combinations to recognize different pathogens, learning the structure and specificity of the antibody and the role they play in fighting pathogens. The set of kits for a classroom are distinct, with kits sharing some, but not all, variable regions. This feature allows for modeling of herd immunity and how different infections spread through a community depending on vaccination rates. This tangible model therefore can convey to students how vaccines elicit protection against pathogens at both an individual and population level. Inclusion of this learning activity during STEM outreach events or integration into classroom curriculum provides an opportunity for early educational intervention that would promote vaccine literacy in our communities.
The Use and Creation of Analogies as a Teaching Tool for Understanding Immunology
Authors: Bernard Aimee Pugh , Spencer Brady L 
Published: August 2023

Abstract
Utilizing existing knowledge of the familiar and known can build associations toward learning, understanding, retaining, and communicating complex concepts. The use of analogies while teaching complex concepts allows the unknown to become familiar and act as an aid toward deeper understanding. Analogies were used as a teaching tool during an immunology course for dental, medical, physician assistant, and graduate students to explain complex concepts. Analogies were used to communicate and enhance the learning and retention of a wide variety of complex concepts and included, but was not limited to, those related to B cell development and activation and the modifications (i.e. somatic hypermutation, affinity maturation, isotype switching) within the germinal center reaction. Analogies were also used to provide students with a teaching tool that they could imitate to create analogies to enhance their understanding and communication of complex concepts. The impact of learning complex concepts through the use of analogies resulted in self-reported increased confidence in understanding and retention of the material. Students reported that learning from and working with analogies not only enhanced their learning of the content but also provided them with a solid foundation from which to build and augment complex concepts with increased detail and added complexity toward a deeper and more nuanced understanding of complex concepts. The incorporation of analogies into the learning process augments scientific communication skills and acts as a model for effective communication while speaking to future patients about medical conditions and/or associated treatments and the general public about scientific discoveries and advancements.
NA
Simulated lab module to teach vaccine biology: From disease transmission to vaccine efficacy, all in a matter of three lab sessions
Authors: Kucknoor Ashwini S 
Published: August 2023

Abstract
Since the COVID-19 pandemic, it has become very important to teach undergraduate students at all levels, about disease transmission and vaccine biology. Just using lectures and reading assignments on these topics often will not be very effective for the student learning. In resource limited undergraduate teaching environment, it is often not possible to use advanced immunology lab techniques. To combat this problem, a lab-module was incorporated into the undergraduate immunology course. In this module, students will follow the process of vaccine development from the identification of a novel disease through the creation and clinical testing of a vaccine This hands-on module was run over the course of three-week lab period, including important concepts of disease transmission, disease diagnosis, mRNA vaccine development, vaccine efficacy and herd immunity. All the exercises included paper-simulations and simulated samples using sodium hydroxide pellets. Overall concepts of innate and adaptive immunity, and detailed concepts like antigenic epitopes, primary and secondary immune responses, and booster doses are emphasized. Students also learn to design mRNA vaccines using gene sequences of Coronavirus spike protein. They also learn principles of ELISA and phases of clinical trial of a novel vaccine. A survey was conducted at the end of the module to evaluate the student learning and student responses to this module. 90% of the students in class were very pleased with this module and stated that this module helped them consolidate their understanding of vaccines. This module can also be modified to be used in a molecular biology or upper-level microbiology courses, with minimum resources.
None
Meta-Lecture: The educational experience of reversed roles
Authors: Ghittoni Raffaella S 
Published: August 2023

Abstract
According to Bloom’s taxonomy classification create, meant as the production of new and original work, represents the highest and most advanced level of cognitive domain in the learning process. Through creative expression students are encouraged to demonstrate their knowledge by combining elements together and by building something coherent, tangible or conceptual.
Meta-Lecture is intended as a non-traditional method to assess mastery of course concepts incorporating short lectures prepared by students, individually, in pair or in a small group, on selected topic, with emphasis on application of course content. This pedagogical approach in teaching is suitable for undergraduate introductory courses as well as for more advanced courses. It represents a student engagement method in both face-to-face and hybrid environment, that aims to improve student commitment and class participation.
Through this alternative method, by simulating a professional environment such as public speaking, poster and seminar scientific presentation, students benefit from the experience of reversed role and from instructor’s and audience feedback on the individual evaluation.
This report provides introduction to the Meta-Lecture assignment, guidance on the feedback analysis and discussion on the learning process.
Trick or Treat-Use of ChatGPT in Education
Authors: Fazal Nadeem , Qasmieh Samah , Graefen Bahar 
Published: August 2023

Abstract
ChatGPT, a free and easy-to-use AI search tool has put Educators scrambling to preserve learning. An education technology company says ChatGPT can be thought of as a “virtual best friend”. ChatGPT launched last November as part of a larger set of technologies developed by the San Francisco-based company OpenAI is part of a new generation of AI systems that can have a discussion and create written work. Millions of people have played with the tool over the past month. Many school systems in the U.S. are still deciding how to set policies on the use of AI programs and how they can be used. Its launch came with little guidance for how to use it. But there is no stopping a student from using ChatGPT from home or on a personal device. We planned to work with both educators and students to learn how people are experimenting with ChatGPT in the real world. Academics are raising tough questions about the future of AI in education. We concluded ChatGPT became so popular quickly across the globe because it is one of the first AI technologies of its kind to be available to the public in a way the public can understand it. We surveyed a global educator and student population about ChatGPT. We report that out of 100 respondents, 85% know about it, 80% are keen to use in education, 80% are still trying to sign up but report high internet traffic to hinder their registration. Finally, younger generation are more willing to experiment this tool, when it becomes available. Nevertheless, it was a talk of first day of spring semester. An OpenAI spokesperson said the company is already working with educators to address their concerns about ChatGPT. We conclude that using such a tool doesn’t build critical-thinking and problem-solving skills which are essential for academic and lifelong success.
Fulbright Association and CTRE Chicago State University, Chicago, IL
Enhancing immunology based health sciences education for addressing health inequities - in the context of COVID-19
Authors: Sika-Paotonu Dianne 
Published: August 2023

Abstract
Māori and Pacific peoples in Aotearoa/New Zealand and the Pacific Region, remain disproportionately and inequitably impacted and affected by a number of adverse health conditions. The global COVID-19 pandemic exacerbated pre-existing inequities in health for different groups, including Māori and Pacific peoples. The consideration of addressing health inequities for Pacific peoples in the context of immunologically relevant health conditions, was explored in the online learning setting for the health sciences students. This work employed use of a Pacific method and means of communication and dialogue, known as Talanoa, that was adapted for the online learning setting as a result of the COVID-19 pandemic. The Talanoa approach was utilised as a tool for students to try and gain better understanding of how to engage, communicate and tackle health inequities appropriately and effectively for Pacific peoples. Undergraduate health sciences students received instruction into the Talanoa approach for communication within the Pacific setting. Online opportunities for presentations and discussion pertaining to developing appropriate solutions to address health inequities for Pacific peoples were facilitated. Students were able to adopt and apply elements of Talanoa in their presentations, discussions and interactions in the online setting. This work highlights the importance of the inclusion of Talanoa, as a means for enhancing online immunology based health sciences education for addressing health inequities appropriately in the context of COVID-19.
Wellington School of Medicine & Health Sciences, University of Otago.
The appropriate application and utilisation of a Pacific model of health and wellbeing for immunology based health sciences education
Authors: Sika-Paotonu Dianne , Taramai Aliesha , Teumohenga Roneima , Tagi Selafi 
Published: August 2023

Abstract
The clinical relevance of immunology in the education setting can be demonstrated by drawing upon examples of specific health conditions affecting populations, but these must be contextualised appropriately. Cancer is a major cause of morbidity and mortality worldwide, and remains a significant health issue that continues to disproportionately impact and affect Pacific peoples in Aotearoa/New Zealand and the Pacific Region. Pacific models of health, clearly and succinctly illustrate key elements important for the health and well being of Pacific communities. Utilisation of these models of health are helpful tools when seeking to address health inequities. This work explored the utilisation of the Fonofale Pacific model of health, to support better understanding of cancer related issues of relevance to Pacific peoples, with immunologically based principles and concepts applicable to the health sciences. This model was also applied as a framework to support better understanding of how to address health inequities appropriately and effectively for Pacific peoples. Undergraduate health sciences students demonstrated understanding and ability in applying and utilising the Fonofale model when developing more appropriate responses for addressing health inequities for Pacific peoples. Students also demonstrated active engagement and participation in the associated activities, with strong interest expressed by some in further work through subsequent research efforts. This work highlighted the importance of the appropriate utilisation and application of a Pacific model of health and wellbeing for immunology based health sciences education and when seeking to reduce health inequities for vulnerable communities.
Wellington School of Medicine & Health Sciences, University of Otago
PI3Kdelta coordinates transcriptional, epigenetic and metabolic changes to promote effector CD8 T cells differentiation
Authors: Cannons Jennifer Leigh , Pichler Andrea C , Villarino Alejandro , Kapnick Senta , Shih Han-Yu , Uzel Gulbu , Su Helen , McGuire Peter , O’Shea John J , McGavern Dorian B , Schwartzberg Pamela 
Published: August 2023

Abstract
Activated PI3K-delta syndrome (APDS) is a primary immunodeficiency caused by heterozygous activating mutations of PIK3CD, resulting in dysregulated immunity, recurrent infections and lymphoproliferation, yet underlying mechanisms behind these phenotypes remain unclear. Using patient samples and Pik3cdE1020K/+ mouse model, we evaluated CD8 cell function both in vitro and in response to infectious agents, assessing cellular phenotypes, metabolism, gene expression and chromatin organization. Pik3cdE1020K/+ CD8 cells exhibited accelerated differentiation to short-lived effectors, associated with increased mTORC1 and c-Myc pathways, as well as altered metabolic, transcriptional and epigenetic circuits characterized by a pronounced IL-2/STAT5 signature associated with heightened IL-2 responses that prevented IL-15 differentiation to memory-like cells. Moreover, Pik3cdE1020K/+ CD8 cells failed to sustain expression of proteins critical for maintenance of long-lived memory cells, including TCF1, and mounted inadequate central memory responses in vivo with enhanced generation of long-lived effector populations. In response to chronic LCMV Clone 13 infection, Pik3cdE1020K/+ mice rapidly die, yet the surviving mice recover more rapidly than WT counterparts. Pik3cdE1020K/+ mice fail to sustain TCF1+ Ly108+ stem-like CD8 cells, with a simultaneous reduction in exhausted cells. However, Pik3cdE1020K/+ mice also have an expansion of CX3CR1+ effector cells associated with increased viral clearance and increased immunopathology. Our data position PI3Kd as a central hub integrating multiple signaling nodes that promote an accelerated effector T cell program during both acute and chronic infections.
This work was supported by the Intramural Research Program of NIAID and NHGRI, NIH.
Patients who develop insulin resistance 4-months post-COVID-19 exhibited higher NETosis and miR-21-5p expression than COVID-19 patients without metabolic alterations
Authors: Cabrera-Garcia Camilo Daniel , Quiroga Romina Andrea , Novoa Sergio Andrés Sanhueza , Cáceres Bárbara Evelyn Antilef , Grez Camila Paz Muñoz , Fraga Marco , Llerena Faryd , Vidal Mabel , Henriquez Mario , Labarca Gonzalo , Garcia-Hidalgo Maria C , Barbé Ferran , De Gonzalo-Calvo David , Verdugo Ricardo , Nova-Lamperti Estefania , Fernandez Liliana Lampert 
Published: August 2023

Abstract
Post COVID-19 has been associated with alterations in the glucidic metabolism and the presence of metabolic-related microRNAs (miRNAs). Since neutrophils response depends on glycolysis, it is unclear whether the formation of neutrophil extracellular traps (NETosis) is also affected in post COVID-19 patients that developed insulin resistance (IR) post infection. In addition, miR-21-5p has been described as a direct gene regulator of the innate immune response against COVID-19 and the presence of IR. In this study, we evaluated NETosis at 4-months post-COVID-19 and its association with the development of IR and the expression of circulating miR-21-5p. Sixty post-COVID-19 patients were recruited from Víctor-Rios-Ruiz Hospital, and post COVID-19 was evaluated 4-months after acute phase. Serum samples were used to determine biochemical parameters. NETosis was measured in patients at basal condition and in response to TLR agonists using flow cytometry. miR-21-5p expression was measured with RT-qPCR. From our cohort, 19 patients were excluded because of they had IR or type 2 diabetes mellitus before COVID-19, 25 patients developed new IR and 16 remained without glucidic alteration. Our analysis showed that COVID-19 patients with IR-Post-COVID-19 had a significant increment of NETosis in basal condition, reducing the capacity to respond efficiently to TRL3/7/8 agonists. We also found a significant increment of miR-21-5p expression in IR-Post-COVID-19 patients and a significant and positive correlation between miR-21-5p and vital NETosis. These results demonstrated that patients who developed IR post-COVID-19 exhibited higher basal NETosis and higher miR-21-5p expression in comparison with patients without alterations.
Supported by grants from PROYECTO COVID1005, ACT210085, Fondecyt Regular 1211480, Instituto de Salud Carlos III (COV20/00110, CP20/00041), Programa de donaciones “estar preparados” UNESPA (Madrid, Spain), Fundación Francisco Soria Melguizo (Madrid, Spain).