bluuebunny/crossref_metadata_2025_split huggingface dataset:
Teaching Immunology in an Integrated System-Based Undergraduate Medical Curriculum using Team-Based Learning (TBL) in the Virtual Classroom: A Learning Experience
Authors: Benoit Lora , Qureshi Mahboob 
Published: February 2023

Abstract
Teaching immunology in the absence of a traditional lecture format presents certain challenges that require special consideration. In part because immunology is often identified as one of the most difficult pre-clinical biomedical courses, requiring a comprehensive understanding of cellular and molecular biology, genetics, anatomy, and infectious diseases and because it is presented in the context of an exclusive vocabulary. To help address the challenge of teaching immunology in the context of the SARS-CoV-2 Pandemic, we developed a four-week, 1st year medical school immunology course using a mostly active learning type modality that could be effectively delivered virtually. In particular, the course content was delivered using a combination of ZOOM, HoloLens, InteDashboard, Brightspace, and the Panopto™ Video platform. Most of the content was delivered using the Team-Based Learning (TBL) pedagogy which incorporated clinically oriented exercises that inspired and engaged students in achieving a mastery of immunology while honing their critical thinking skills; thus, efficiently preparing them for future clinical practices and licensure exams while avoiding an overwhelming perception of the course. Despite the inherent limitations of virtual delivery, the outcome of the course was an unexpected 100% pass rate. A description of the content, course design, formative /summative assessment methods as well as category performance on exams is provided. The expressed perception of the students is reported as are opportunities for improving the educational experience.
Disadvantaged students at minority serving institutions became disproportionally affected by the current COVID-19 pandemic.
Authors: Renteria Sahira , Stempek Ryan , Olk Sandra R , Fazal Nadeem 
Published: February 2023

Abstract
Learning has been a complex human skill. Humans have gone through a gradual learning experience spanning hundreds of years. Never in the history mankind have been tested with learning a tsunami of information in a very short period. Last couple of decades have stressed out not only the neurobiology of learning but tested the maximum limits of human capacities. If not all, some of the population group like students have burnt out. To add further stress to depleting limits of human capacities the current pandemic totally exhausted even their reserves. We at College of Pharmacy Chicago State University tested and other stressor being minority serving university and having a major population of disadvantage students. We did a survey of under graduate students and asked them this question to identify only one and most important challenge they faced in this time of pandemic induced remote learning. Not to our surprise we found that a statistically significant number of students declared that the cost of paying for technology to survive in this remote learning was the major factor that impacted their learning and lead to a major challenge for them. Most of the students suffered financial stress with loss of jobs, declining college loans, lack of motivation for a successful career. More specifically these disadvantage students could not keep up with the rising cost of wifi, laptop, cell phones and opting for additional online learning tools. To give an example, one student told us that she would go to near by Starbucks to get online assignments done in a timely manner. In the current lock down even the public libraries are closed and students struggle. Our study suggests that the universities set aside a special budget to financially help these disadvantage students.
Pan-academic in Pandemic! Remote learning goes viral, mostly out of control.
Authors: Fazal Nadeem , Alakbarova Gulgaz 
Published: February 2023

Abstract
A pandemic of viral origin has caused a pan-academic in the educational world as well. The younger student population though felt safe owing to their robust immune response but took a big hit in their emergency academic response to COVID-19 times. A pandemic needed a pan-academic response. The students were obviously not prepared and equipped for such an abrupt behavioral adaptation, with no second choice offered. Now it has evolved into global research in progress and Educators are experimenting on no-so-willing students. We studied a robust group of 138 medical students across 3 medical schools in Azerbaijan and gathered enormous amounts of data set points. Some of the major takes from our surveys proved the dichotomy and split among the medical students have in terms of coping with the unprecedented circumstances. The challenges included using combination of distance-learning platforms, i.e., synchronous lessons (similar to zoom sessions), pre-recorded lectures, powerpoint presentations, question-banks, etc. A significant difference was found between time spent on online platforms before COVID-19 (10.86%), as compared to (46.37%) during lock-down, while average students were online &gt;15 hours per week. The commonly perceived barriers to using online teaching included, poor internet connection (72.5%), cost of technology, and distractions while studying at home (56.5%). For one group of students remote learning seemed cheaper and flexible than traditional class (saved rent, food, traffic woes). Most of the students’ settled for hybrid learning, thus giving equal weight to in-class vs remote learning experiences. We conclude that there seems to be no one size fits all-approach, we suggest a blended, hybrid, multi thronged system.
Adaptation of a CURE course aimed at characterization of host-pathogen interactions for on-line learning
Authors: Snyder Michelle , Snyder Greg A 
Published: February 2023

Abstract
Course-based undergraduate research experiences (CUREs) aim to engage a large, diverse group of students in authentic research, promote student research skills, content knowledge, scientific literacy, critical thinking and analysis skills, support student self-efficacy, and at the same time provide a means to advance faculty research productivity. Addressing each of these varied goals of a CURE course is a challenge, and became even more challenging when classes were forced on-line for the COVID-19 pandemic. In Fall of 2020, we adapted our CURE course, which seeks to engage students at Towson University with research ongoing at the University of Maryland, School of Medicine, for virtual learning. To move the course on-line, we focused on activities that could easily be adapted to a virtual environment, such as those focusing on bioinformatics analysis, research design, data analysis, scientific writing and on-line lab simulations. Students were tasked with becoming ‘project managers’—designing hypotheses and protocols and choosing experimental variables and controls, while instructors and an undergraduate learning assistant carried out the experiments, videotaping so students could become familiar with the techniques. While the drawbacks of the virtual CURE course were many, including the lack of student involvement in hands-on bench work, benefits of the virtual CURE included more time and attention devoted to critical skills such as research design, data analysis and scientific writing. Future designs of CURE courses may benefit from increased attention to these skills, even upon return to in-person learning.
Active learning strategies incorporating Immunology based teaching examples for Health Sciences Education
Authors: Sika-Paotonu Dianne 
Published: February 2023

Abstract
Clinically relevant Immunology based teaching examples for postgraduate Health Sciences education offer valuable opportunities to support and reinforce understanding and learning of basic principles. The appropriate reference to significant health conditions as teaching examples that are of immediate relevance to specific population groups requires care. Active learning strategies that incorporate Immunology based teaching examples and references to Māori and Pacific population groups living in Aotearoa/New Zealand and the Pacific Region, are much needed to support Health Sciences education. The autoimmune condition known as Acute Rheumatic Fever (ARF) resulting from untreated Group A Streptococcal (GAS) infection of the throat and skin, and subsequent cardiac damage known as Rheumatic Heart Disease (RHD) that occurs if repeated or severe untreated ARF episodes happen, disproportionately affect Māori and Pacific population groups living in Aotearoa/New Zealand and the Pacific Region. These conditions were incorporated into active teaching approaches to support postgraduate Health Sciences students, with appropriate cultural context. Students participating in postgraduate classes that utilised active learning strategies with appropriate incorporation and reference to the ARF/RHD setting, demonstrated high levels of engagement and in-class participation, and as evidenced by formal and informal student feedback, fostered in-depth understanding of the Immunology principles being taught. This highlights the importance of appropriate reference and context for active learning strategies that incorporate Immunology based teaching examples when relating to specific population groups.
Mesenteric lymph node priming licenses intestinal CD103+ CD8 tissue-resident memory T cell development
Authors: Qiu Zhijuan , Khairallah Camille , Chu Timothy H. , Imperato Jessica N. , Romanov Galina , Puddington Lynn , Sheridan Brian S. 
Published: February 2023

Abstract
CD8 tissue-resident memory T (TRM) cells provide front-line protective immunity at barrier tissues; however, mechanisms regulating their development are not completely understood. Priming dictates the migration of effector CD8 T cells to the tissue, while factors in the tissue induce in situ TRM cell differentiation. Whether priming also regulates in situ differentiation of CD8 TRM cells has not been addressed. Here, we demonstrate that T cell priming in the mesenteric lymph nodes (MLN) was the principal determinant of CD103+ CD8 TRM cell differentiation in the intestine. In contrast, CD8 T cells primed in the spleen were inefficient at differentiating into intestinal CD103+ TRM cells. Moreover, both CD103− and CD103+ naïve T cells were highly efficient in differentiating into CD103+ TRM cells in the intestine after priming in the MLN, suggesting preconditioning of naïve T cells by TGF-b during homeostasis had little impact on intestinal CD103+ TRM cell differentiation. We further demonstrate that MLN priming initiated CD103+ CD8 TRM cell signature gene expression and licensed rapid CD103+ CD8 TRM precursor cell differentiation in response to factors in the tissue by providing retinoic acid signaling to CD8 T cells. Thus, MLN priming is specialized to license intestinal CD103+ CD8 TRM cell development.
Accumulation of Tissue Resident NK cells in Female Genital Tract during follicular phase of HIV seronegative women
Authors: Govindaraj Sakthivel , Babu Hemalatha , Endress Daniel , Rahman Sadia J , Ibegbu Chris , Kozlowski Debra Susan , Doraivelu Kamini , Herring Gina Bailey , Mehta Christina , Smith Alicia K , Haddad Lisa , Velu Vijayakumar 
Published: February 2023

Abstract
Female sex hormones are known to regulate the immune functions of the female genital tract (FGT). While the majority of immune cells found in the FGT are T cells and Natural Killer cells (NK cells), very few studies have focused on NK cells in the FGT in contrast to numerous studies focusing on T-cells. Here, we characterized the distribution, phenotype and function of NK cells in FGT of HIV seronegative women using different mucosal sampling methods; cervicovaginal lavage (CVL), endocervical cytobrush (CB), and cervicovaginal biopsy and compared them to blood. We isolated cells from blood and FGT and performed multi-color flow cytometry to identify cellular phenotypes. First, we looked at the distribution of CD56brightand CD56dimpopulations of NK cells across the samples and found that CD56brightNK cells were lower in the FGT tissues compared to blood. Between the CD56brightand CD56dimpopulations, the CD56dimpopulation was significantly reduced in the follicular phase compared to the luteal phase in tissues. The NK cells within the FGT samples express higher levels of tissue resident markers CD69 and CD103. The co-expression of CD69+CD103+ markers seem to be significantly higher in follicular phase compared to luteal phase in tissues. These cells have high proliferative capacity with high levels of HLADR expression, suggesting that these cells are highly functional and activated. The gut tissue homing marker alpha4beta7 expression significantly reduced in the follicular phase, however other homing markers CCR5 and CCR7 expression were elevated in the follicular phase. Altogether, these data demonstrate that FGT is enriched with tissue resident NK cells with high activation and proliferation profile with distinct homing potential.
NKG2A educates uterine NK cells to optimise pregnancy outcomes in humans and mice
Authors: Shreeve N , Traherne JA , Sovio U , Hawkes D , Depierreux D , Huhn O , Jayaraman J , Horowitz A , Ghadially H , Perry JRB , Moffett A , Sled JG , Sharkey AM , Colucci F 
Published: February 2023

Abstract
The conserved CD94/NKG2A receptor binds HLA-E in humans and Qa-1 in mice. Besides inhibiting natural killer (NK) cell activation, NKG2A drives NK-cell education, a process influenced by HLA-B alleles that promotes NK cell function. In human populations some individuals are genetically programmed to favour NKG2A education and have more robust NK cell function. NKG2A is expressed by nearly all human and roughly half mouse uterine NK cells (uNK), but the importance of NK-cell education in physiology is unknown.
Here we show that NKG2A was required for uNK cell-education in dams. Genetic ablation of NKG2A caused sub-optimal vascular responses in pregnancy, increased rate of smaller fetuses, which grew asymmetrically with abnormal brain development, and changes in placental gene expression consistent with stress. These are features of the human syndrome pre-eclampsia. In a genome-wide association study of 7,219 cases and 155,660 control pregnancies, we found that the maternal HLA-B allele that does not favour NKG2A education, was associated with a 7% greater relative risk of pre-eclampsia (P=0.005, OR= 1.07).
These results establish the relevance of NK cell education in physiology and show that the maternal HLA-B –&gt; HLA-E –&gt; NKG2A pathway contributes to healthy pregnancy and may influence offspring health.
Zom-biecoming: Single-Cell RNA-seq reveals senescence-like features of alveolar macrophages during aging
Authors: Wu Yue , Zhu Bibo , Zhang Ruixuan , Wang Zheng , Goplen Nick P. , Gao Xiaochen , Li Ying , Cadani Amber , Braciale Thomas J , Sun Jie 
Published: February 2023

Abstract
Alveolar Macrophages (AMs) are unique innate immune cells that reside in the alveolar space and accommodate the ever-changing need of the lungs against internal and external challenges. During homeostasis, AMs maintained themselves through self-renewal without the need for the input of adult hematopoietic stem cells. Currently, little is known about how aging influences AM dynamics, heterogeneity and transcriptional profiles. Here, we identified the transcription factor, Cbfb, has indispensable role in AM self-renew ability. In the bone marrow chimera mice with genetic knock-out of Cbfb specifically in the myeloid compartment, AMs displayed reduced proliferation and an immature phenotype. Moreover, with the analysis of the combined scRNA-seq data of the FACS sorted AMs (CD11+ Siglec F+) in young(~8w) and aged(~2y) mice, we discovered that despite for the similar transcriptome in the proliferating cells, the AMs from the aged mice had reduced embryotic-stem cell (ESC)-like features. The AMs from the aged host also had reduced DNA repair ability, which could contribute to their impaired capacity to pass through the cell cycle checkpoints and elevation of senescence markers. In accordance with the analysis, we observed reduced number of AMs in the aged mice, which had abrogated self-renew ability and were more sensitive to the reduction of GM-CSF. Increased b-galactosidase staining was also observed in the AMs from the aged mice. Taken together, we concluded that AMs in the aged host harbor a senescence-like phenotype. Further investigation is warranted for the mechanism and pathophysiological consequences of the accumulation of AMs with senescence-like phenotype in the aged host.
Large scale analysis of smoking-induced changes in the tumor immune microenvironment
Authors: Alisoltanidehkordi Arghavan , Qiu Xinru , Jaroszewski Lukasz , Sedova Mayya , Iyer Mallika , Li Zhanwen , Godzik Adam 
Published: February 2023

Abstract
Here, we expanded the recent knowledge on the immune landscape of cancer by performing a comparative analysis of tobacco smoking-induced changes in the populations of major immune cell types between smokers and never-smokers (people who have never smoked). To investigate the immune response of smokers and never-smokers, the relative abundance of immune cell types was calculated by both CIBERSORT and xCell based on TCGA RNA-seq data. We further validated the findings using publicly available bulk RNA-seq and single-cell RNA-seq data from cohorts of cancer patients other than TCGA cohort. We showed statistically significant smoking-induced changes in immune cell populations in all studied cancers. The increase in plasma cell populations and the changes in the ratio of activated to resting immune cell types were the most consistent features distinguishing smokers and never-smokers across different cancers, with both being correlated with survival outcomes. We found that the tobacco-induced changes in populations of immune cells were not as marked in cancers of tissues that are not directly exposed to smoke as in lung cancers and head and neck cancer (LUAD, LUSC, and HNSC). However, the significant differences in survival in several cancer types suggest that even a small shift in the frequency of immune cell types might result in adverse outcomes. We also showed that smoking-induced changes in the patterns of immune cell populations and their correlations to survival outcomes are stronger in female smokers than in males. In general, the findings of this study suggest that certain immune cell types could potentially be used as common prognostic markers and therapeutic targets for active smoker patients.
The contradictory functions of NLRX1 in breast cancer allow for suppression or promotion of tumor growth and metastasis in a cell-specific manner.
Authors: Nagai Margaret A , Hendricks-Wenger Alissa , Fletcher Endia , Khan Imran , Morrison Holly , Allen Irving C 
Published: February 2023

Abstract
Breast cancer is a deadly malignancy that is responsible for 15% of all cancer-related deaths in women. Examining the innate immune system in breast cancer has revealed the importance of pattern recognition receptors, such as NLRX1, in disease progression. NLRX1 has been implicated as a tumor suppressor because it suppresses inflammation by many mechanisms, including by inhibiting the NF-κB pathway. Here, we investigated the potential of NLRX1 as a tumor suppressor in breast cancer when it is expressed either by healthy host cells or cancer cells. To determine the role of NLRX1 in healthy host cells, we used the 4T1 breast cancer model in WT and Nlrx1−/− (KO) mice. KO mice exhibited increased lung metastasis and tumor size compared to WT mice. Gene expression data revealed increased expression of proliferation, survival, growth, invasion, and metastatic genes in tumors from KO mice compared to WT mice. Thus, NLRX1 in healthy host cells is protective against breast cancer tumor growth and metastasis. Next, we investigated the role of NLRX1 in breast cancer cells. 4T1 cells were transduced to overexpress NLRX1 and injected into WT (WTOE) and KO(KOOE) mice. Transduction controls were also generated and injected into WT (WTOE-CTL) and KO (KOOE-CTL) mice. KOOE mice developed larger tumors than KOOE-CTL mice. KOOE mice also developed more lung metastasis compared to WTOE, WTOE-CTL, and KOOE-CTL mice. This suggests NLRX1 in breast cancer cells contributes to tumor growth and metastasis, which directly contradicts the function of NLRX1 in healthy host cells and demonstrates a cell-specific function of NLRX1 in breast cancer. These cell-specific differences are critical foundations for the development of NLR-based breast cancer therapies.
Lung tumor immune evasion mechanism in Non-small cell lung cancer (NSCLC) targets pSTAT5 in CD4+CD25+FoxP3− T effector cells
Authors: Tausche Patrick , Trufa Denis I , Geppert Carol-Immanuel , Rieker Ralf J , Sirbu Horia , Finotto Susetta 
Published: February 2023

Abstract
The mechanisms of lung cancer evading the immune system are still not fully understood. As regulatory T cells (Tregs) exhibit a pro-tumoral function they are in focus of immunotherapies. Peripheral Treg differentiation is driven by TCR and its co-stimulation. A further crucial signal displays the binding of IL-2 to the high affinity receptor CD25 with downstream involvement of Signal Transducer and Activator of Transcription 5 (STAT5). STAT5 activation as well as TGF-beta stimulation in the periphery leads to expression of the Treg key factor FoxP3.
In this study, we wanted to investigate the role of STAT5 and its activated status via phosphorylation (pSTAT5) within lung cancer. We thus isolated peripheral blood mononuclear cells (PBMC) from NSCLC patients and healthy donors. PBMCs were cultured under different stimulation conditions for 4 days and analyzed by FACS.
Here we found CD4+ T cells with high induction of pSTAT5A and CD25 upon aCD3 and aCD28 antibody treatment. Moreover, CD4+CD25+FoxP3+ Tregs were detected under T cell activating conditions, and were found to be increased by TGFβ in smokers and NSCLC patients. The Treg population was further inducible by adding low doses of IL-2 while CD4+CD25+FoxP3− effector T cells decreased in the presence of TGFβ. Our findings point to an immunosuppressive microenvironment induced by the tumor with increased TGFβ and reduced IL-2 forcing effector T cells into a Treg state. These preliminary data suggest that current immunotherapy by aCD3/aCD28 antibody treatment could be improved by an additional blockade of TGFβ and induction of IL-2 levels. This treatment would result in an increase of CD4+CD25+pSTAT5+FoxP3− effector cells and a reduction of CD4+CD25+FoxP3+STAT5+ Tregs.