bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Meditation to Reduce Stress, Anxiety, and Depression in Nursing Students
Authors: Holden Shohini , O'Connell Kathleen A. 
Published: August 2023

Background:
Nursing students experience higher rates of mental health issues than other college students. This study examined the effect of a mindfulness meditation intervention on nursing students' levels of self-reported depression, stress, and anxiety.

Method:
This randomized, experimental study implemented an online mindfulness meditation intervention for an experimental group of nursing students and provided nursing news modules for a control group of nursing students. Participants in experimental and control groups completed the Depression, Anxiety, and Stress Scale online before and after completing 4 weeks of audio modules.

Results:
Results showed a statistically significant decrease in reported scores for depression, stress, and anxiety in the experimental group.

Conclusion:

This study demonstrated the potential benefits of implementing an online mindfulness meditation intervention to support and improve mental health for nursing students.

[
J Nurs Educ
. 2023;62(8):443–449.]
Teaching Prelicensure Nursing Students Reasoning in Clinical Experiences: A Pilot Study
Authors: Fontenot Justin , Leigh Gwen , Watson Cynthia , Stueben Frances , Arceneaux Stephanie , Johnson Sharonda , St. Romain Arielle 
Published: August 2023

Background:
Clinical experiences are foundational learning components for prelicensure nursing students. Given the complexities of modern nursing practice in an aging America, clinical educators must teach nursing students to reason when engaging in patient care. Contemporary pedagogy to enhance reasoning relies on case studies and simulation. Specific and standardized methods for clinical education are largely absent in the literature.

Method:
This pilot study measured the clinical reasoning ability of nursing students using the Health Sciences Reasoning Test (HSRT). Participants completed the test before their first clinical day and again after their last clinical day. Pre- and posttest HSRT scores were analyzed by control and intervention groups as well as student levels.

Results:
Posttest HSRT scores improved significantly in the intervention group at the end of the semester.

Conclusion:

The PREP framework is a novel approach to clinical education and improved the clinical reasoning of prelicensure nursing students.

[
J Nurs Educ
. 2023;62(8):467–470.]
T-bet overexpression modulates CAR T cell effector functions
Authors: Cimons Jennifer , Degolier Kole R , Kohler Mark Eric , Fry Terry 
Published: August 2023

Abstract
Adoptive transfer of T cells modified with a chimeric antigen receptor (CAR) are highly effective in patients with hematologic malignancies. However, many patients relapse and CAR T cells have shown minimal efficacy against solid tumors. Our lab and others have shown that standard CAR designs fail to promote differentiation into canonical T cell subsets. CAR T cells generate both type-1 and type-2 cytokines simultaneously, challenging the traditional paradigm that Th1 and Th2 differentiation programs are mutually exclusive. We sought to control this by overexpressing the transcription factor T-bet to drive a more canonical type-1 effector response. CD28-costimulated CAR T cells overexpressing T-bet showed a reduction in type-2 cytokine production. In an immune-competent syngeneic mouse model of B cell acute lymphoblastic leukemia, T-bet overexpressing CAR T cells showed increased expansion, increased generation of KLRG1+CD127− effector T cells, and decreased expression of exhaustion-associated markers PD1, TIM3, and LAG3 through the initial CAR T cell expansion and contraction phases Despite this, Tbet overexpression drove late CAR T cell hypo-functionality and leukemic relapse. However, in 4-1BB-costimulated CAR T cells, which tend to have a weaker effector response than CD28-costimulated CAR T cells, T-bet overexpression led to increased CAR T cell potency, prolonging survival over mice treated with a 4-1BB-costimulated CAR. Furthermore, T-bet overexpression led to increased CAR T cell polyfunctionality against low-antigen density leukemia when compared to standard CAR T cells. These results demonstrate the potential of T-bet-overexpression as a strategy to modulate the strength of the CAR T cell effector response.
Supported by funding from the University of Colorado School of Medicine Human Immunology and Immunotherapy Initiative
Novel stem cell treatment to combat pediatric inflammatory response during cardiopulmonary bypass surgery
Authors: Asbury Julie Marie , Anderson Alanna , French Beth 
Published: August 2023

Abstract
Cardioplegia and exposure to the heart-lung machine required in cardiopulmonary bypass induce a systemic inflammatory response. Adverse effects cause longer ICU stays, higher medical costs, and worsened mortality and morbidity, especially in neonatal and pediatric populations. nCPCs have been shown to have regenerative and anti-inflammatory properties when introduced in animal studies as a treatment. Surgeons at UMB performed cardiopulmonary bypass surgery on non survival porcine subjects with a control and treatment group of 6 porcine subjects in each. NDMU tested and analyzed serum samples of the subjects for immunological markers or interleukins. The results revealed that the treatment does seem to have an effect on the pro-inflammatory cytokines of TNF-α, IL-1β, and IL-6. TNF-α, IL-1β, and IL-6 concentrations decreased significantly from 3124 to 1480 pg/mL, 8319 to 2714 pg/mL, and 18,011 to 10,825 pg/mL, respectively. Furthermore, the treatment also has an effect on IL-10, an anti-inflammatory cytokine, noted by an increase from 289 to 328 mg/mL. Overall, the treatment seems to have a greater effect on the macrophage immune response, while it seems to have little to no effect on the neutrophil immune response. Surgeons are currently working on survival porcine subjects. Moreover, H&E staining and RT-qPCR of samples will be performed to determine the localization of damage and relative expression of the cytokines of interest.
Modified adenovirus induces antigen specific T cells and effector memory T cells in mice
Authors: Sieling Peter A , Golovato Justin , Niazi Kayvan , Rabizadeh Shahrooz 
Published: August 2023

Abstract
We engineered a novel adenovirus with a modified capsid for use as an integrated anticancer gene therapy and to circumvent pre-existing adenovirus immunity. The modified adenovirus, SynBAd, when administered intravenously, induced antigen-specific CD8 T cell immunity in the liver of mice (C57BL/6) and a splenic population of effector memory T cells at levels equivalent with those induced by human Adenovirus serotype 5 (Ad5). Although the virus elicited equivalent liver and splenic T cell responses, SynBAd did not elevate liver enzymes as commonly seen with Ad5. SynBAd bound factor X with similar affinity to Ad5, though it localized preferentially to the spleen relative to Ad5, suggesting greater systemic immune stimulation. CD8 T cells in the liver and spleen increased with SynBAd administration, indicating that the virus acts as a potent mobilizer of T cells. Although SynBAd is a potent immunogen, antibodies generated in mice immunized with Ad5 only weakly neutralized SynBAd infection in vitro, suggesting that preexisting Ad5 antibodies will not dramatically influence SynBAd efficacy. Localization of the adenovirus after administration, activation of antigen specific T cells, and mobilization of effector memory T cells, suggest that this approach will promote an antitumor immune response that could be used in multiple tumor indications.
IMPACTing autoimmunity through dual targeting of antigen presenting cells and T cells via inhibitory receptor agonism
Authors: Grebinoski Stephanie J , Lutz Stephen , Cianci Michael , Borah Minasri , Stanlie Andre , Goydel Rebecca , Visweswaraiah Jyothsna , Higginson-Scott Nathan , Otipoby Kevin , Cipolletta Daniela 
Published: August 2023

Abstract
Autoimmune diseases are triggered by a critical break in peripheral tolerance, thereby allowing the immune system to target and destroy host tissues. Tolerance mechanisms, such as inhibitory receptor (IRs) on T cells, can greatly influence autoimmune disease progression and outcomes, representing an opportunity for therapeutic intervention. Indeed, evidence in both animal models and patients suggests that IRs play a major role in limiting autoimmunity. Immunotherapies targeting IRs have revolutionized the treatment of many cancers and provided evidence that IR modulating therapeutics can significantly impact patient outcomes. However importantly, analogous IR-targeted autoimmune therapeutics have just begun to be tested.
Despite interest, IR agonist antibodies have proven difficult to generate. Optimal agonist antibodies require IR superclustering, which is not efficiently induced by Fc-null antibodies. Successful agonists will likely rely on simultaneous Fc (constant region) tethering on antigen presenting cells (APC), thereby allowing efficient IR superclustering and downstream signaling. Current agonistic antibodies targeting IRs contain an IgG1 wild-type Fc, which by binding both activating and inhibitory Fc receptors can trigger unwanted production of inflammatory cytokines by APCs. Here we show that antibodies binding selectively FcγRIIb, support superior agonism compared to IgG1 wild-type antibodies and mitigate potential liability of current IR agonists under clinical investigation. Indeed, dual targeting of the APC and T cells shows promising pre-clinical results and will be used to create novel IR agonists.
Large-scale analysis of CoVIC antibodies by a global consortium identifies predictors of in vivo protection
Authors:   Members of the Coronavirus Immunotherapeutic Consortium, Jarjapu Mahita ,   CoVIC-DB Team, Saphire Erica Ollmann , Peters Bjoern 
Published: August 2023

Abstract
The Coronavirus Immunotherapeutic Consortium (CoVIC) was established to develop prevention and therapeutic strategies against SARS-CoV-2 that could be used in low- and middle-income countries. The CoVIC compiled a unique panel comprising nearly 400 candidate therapeutic antibodies contributed by 60 groups in industry, academic, and government settings. All antibodies in the CoVIC panel were first blinded at the CoVIC headquarters at the La Jolla Institute for Immunology through the assignment of a code name. Identical sets of antibodies were then sent under the assigned code names to seven different partner reference labs that carried out side-by-side, standardized analyses of binding affinity, epitope location, high resolution structures, pseudovirus and authentic virus neutralization, in vivo protection, and Fc-mediated effector functions. The reference labs deposited their data, which was then validated and made publicly accessible, in the CoVIC database (CoVIC-DB). Using various statistical analyses of the data, we investigated relationships among functional properties of the antibodies. For example, we could discern that binding affinity to the full-length spike is more predictive of neutralization potency than binding affinity to the RBD, and that binding affinity and epitope location together correlates with neutralization. However, neutralization alone is not sufficient to explain in vivo protection in the K18 mouse model of SARS-CoV-2 infection, as other factors such as antibody pharmacokinetics were also important. Overall, the results of this study revealed important insights into antibody properties that are good predictors of in vivo protection by CoVIC antibodies.
COVIC-19 Therapeutics Accelerator (a partnership of Bill and Melinda Gates Foundation), Bill and Melinda Gates Foundation, Mastercard, Wellcome Trust, National Institute of Allergy and Infectious Diseases of the National Institutes of Health, GHR Foundation, FastGrant from Emergent Ventures
Splicing of ultraconserved poison exon elements in RNA binding proteins reprograms the T effector immune response
Authors: Karginov Timofey , Menoret Antoine , Leclair Nathan , Chandiran Karthik , Suarez-Ramirez Jenny E , Karlinsey Keaton , Murphy Patrick , Adler Adam J , Zhou Beiyan , Cauley Linda S , Anczukow Olga , Vella Anthony T 
Published: August 2023

Abstract
Our current understanding of pathways governing the strength and longevity of T cell mediated immune responses primarily focuses on transcriptional and epigenetic changes. However, our prior work demonstrated that optimal T cell effector function is also dependent on RNA binding proteins (RBPs) that carry out post-transcriptional RNA splicing and polyadenylation. Here, we find that a specific family of RBPs, serine- and arginine-rich (SR) RBPs, are significantly upregulated by T cell activation and required for CD8+ T cell mediated responses. SR transcripts contain ultraconserved poison exon (PE) elements that are alternatively spliced and introduce premature stop codons that trigger nonsense-mediated decay. We show that differential splicing of specific RBP PE regions is both induced by TCR stimulation and required for CD8+ T cell activation in both human and mouse. Further, we demonstrate that PEs are cell-state associated by using single-cell RNA sequencing analysis of splicing changes across mouse thymic T cell subsets, in CD8+ T cells over the course of an acute Listeria infection, as well as in human lymphoblastic leukemia, atherosclerosis, and melanoma patient T cells. CRISPR-Cas9 mediated deletion of the PE element of SR-like RBP Tra2β in mouse T effector cells during influenza infection resulted in a significant increase in proliferating and surviving T cells and altered the splicing pattern of critical cell survival, proliferation, and adhesion genes. In total, our work demonstrates a fundamental role for alternatively spliced ultraconserved elements in defining T cell states, controlling T effector-mediated immunity, and altering the T cell response in pathologic conditions.
This work was supported in part by NIH grants AI136955 and R21AI139891 awarded to A.T.V, institutional support, and Boehringer Ingelheim endowed Chair in Immunology.
Early Life Antibiotic Exposures Inhibits Postnatal Enteric Nervous System Maturation and Alters Neonatal Neuroimmune Interactions
Authors: Schill Ellen Merrick , Joyce Elisabeth L , Gaddipati Shreya , Floyd Alexandria N , McDonald Keely G , Rusconi Brigida , Newberry Rodney D 
Published: August 2023

Abstract
The enteric nervous system (ENS) regulates intestinal homeostasis via interactions with smooth muscle, epithelium, and immune cells. To assess the impact of early life antibiotics on postnatal ENS development, we performed neuron specific translating ribosome affinity purification to isolate RNA from control and antibiotic exposed enteric neurons for RNA sequencing. Colonic enteric neurons from antibiotic exposed pre-weaning mice expressed significantly less mature neuron markers, and acquired a more inflammatory cytokine signaling signature (e.g. IL18, MCP-1, TLR4). Immunofluorescence staining and ELISA revealed increased enteric neuron density in antibiotic exposed colons, yet reduced expression of neuronal markers including Tuj1 (neuron specific tubulin), synaptophysin (synapse marker) and acetylcholine. Notably, antibiotics did not affect ENS development in germ free mice. By confocal microscopy, antibiotic exposure appeared to reduce phagocytosis of neuronal cell bodies by macrophages, but phagocytosis of synapses by macrophages was increased. Flow cytometry revealed that antibiotic exposure reduced the proportion of macrophages expressing the “M2” marker CD163 compared to controls. This observation is reminiscent of Hirschsprung disease (HSCR), a congenital absence of the ENS from the distal intestine, which causes intestinal macrophages to adopt a pro-inflammatory phenotype and predisposes patients for HSCR-associated enterocolitis secondary to decreased cholinergic signaling. These data suggest that early life antibiotic exposure disrupts how macrophages participate in postnatal ENS development in a microbiota dependent mechanism.
NIH NIAID U01AI131342, NIH NIDDK P30DK052574, T32DK077653, NIH T32HD43010 American Academy of Pediatrics Marshall Klaus 2022
Dietary fiber and Segmented Filamentous Bacteria interaction with intestinal epithelial cells supports the development of CD4+CD8αα+ intraepithelial T cells
Authors: Marino Naomi Claudette Rodriguez , Rivera-Rodriguez Dormarie E , Royer Charlotte J , Yaceczko Madelyn , Cervantes-Barragan Luisa 
Published: August 2023

Abstract
Double positive intraepithelial lymphocytes (DP IELs) are microbiome induced CD4+CD8αα+ T cells that play a role in maintaining homeostasis and reducing inflammation in the small intestine. While the impact of the microbiome on the intestinal immune system has been extensively studied, little is known about how changes in macronutrients, such as dietary fiber, affect the development of important immune cell populations through changes in the microbiome. Here we show that a diet low in fermentable fiber (LFF) impairs development of DP IELs by reducing MHC-II expression on intestinal epithelial cells (IECs). Bulk RNA sequencing of ileal IECs revealed that LFF fed mice had lower expression of genes associated with the antigen presentation machinery. Subsequently, flow cytometry analysis confirmed increased expression of MHC-II on IECs in standard chow fed mice, which is required for DP IEL development. 16s rRNA sequencing of the microbiota of LFF mice showed that SFB is reduced in these animals. We found that colonizing mice with SFB induces MHC-II expression on IECs and restores development of DP IELs in a fiber-dependent manner. Finally, using the offspring of mice that naturally harbor SFB, we show that MHC-II expression on IECs and IFN-γ levels in the ileum increase gradually over time and correlate with SFB colonization. These results suggest that dietary fiber is required for the development of DP IELs through supporting SFB colonization and increasing expression of MHC-II on small intestinal epithelial cells.
Supported by grants from NIH (1R011DK129950) and startup funds from Emory University
Neuronal cells co-ordinate myeloid-epithelial cell interaction to regulate intestinal inflammation
Authors: Sharma Deepika , Malik Ankit , McGrath Shaina , Zabala Sarah , Yang Daping , Chiu Isaac M , Jabri Bana 
Published: August 2023

Abstract
Epithelial response to injury is coordinated through an intricate interaction with neuronal and myeloid cells, however the signaling modules involved are not well understood. In humans, somatic mutations in Tet methylcytosine dioxygenase 2 (TET2), a DNA demethylase, are commonly observed during ageing in myeloid cells and known to modulate inflammatory responses. Using a mouse model that lacks TET2 in myeloid cells (Tet2ΔLysM), we show that myeloid cells and sympathetic neurons form a signaling nexus that controls differentiation of enterochromaffin cells and serotonin production during colonic inflammation. Under physiological conditions, TET2 restricts IL-1β production by myeloid cells which in turn controls the intestinal sympathetic architecture. During inflammation, IL1R signaling limits sympathetic cues that drive differentiation of enterochromaffin cells through α1-adrenergic signaling. As a result, enterochromaffin differentiation and colitis progression in response to mucosal injury is attenuated in Tet2ΔLysM mice. Further, protection from colitis in Tet2ΔLysM mice is mediated by its catalytic activity, and dependent on sympathetic neurons and IL1R signaling. Adrenergic control of epithelial response and pro-colitic serotonin production is also evident under conditions of physiological stress that leads to increased colitis susceptibility. Overall, our study reveals a sympathetic-epithelial axis that controls the severity of colitis and is modulated by myeloid-derived IL-1β and physiological stress. Our findings may also explain why inflammatory bowel disease in the elderly, where TET2 mutations in myeloid cells are common, is less severe and suggests TET2 activity as an attractive target for IBD.
Supported by the US National Institutes of Health (DK067180) to B.J, the University of Chicago’s Center for Interdisciplinary Study of Inflammatory Intestinal Disorders (C-IID) Pilot & Feasibility Award (NIDDK P30 DK042086) to A.M. and D.S, Crohn’s and Colitis Foundation Career Development Award #964209 to A.M. and G.I. Research Foundation Associates Board Award to A.M. and D.S.
Intestinal Barrier Repair in Giardiasis
Authors: Kosile Rita Taye , Angelova Vanessa V , Pannkuk Evan , Singer Steven M 
Published: August 2023

Abstract
Giardiasis is a common diarrheal disease caused by the protozoan parasite Giardia duodenalis. Acute symptoms can include diarrhea, but infections are often sub-clinical. It is transmitted via ingesting infectious cysts in contaminated food or water. In developing countries, giardiasis is one of the leading causes of growth stunting in children under two years old. Changes in intestinal barrier integrity have been shown to contribute to impaired nutrient absorption, thereby leading to growth stunting. Although intestinal barrier defects have been linked to infection, there is little understanding of barrier repair dynamics post-infection. Previous studies have demonstrated that Giardia infection is associated with dysbiosis in humans and animals. Because Aryl hydrocarbon receptor (AHR) signaling has been shown to promote intestinal repair in other systems, we are exploring the role of AHR in barrier repair following a Giardia infection. We quantified specific microbiome-derived AHR ligands in the plasma of infected C57BL/6 mice and observed a reduction of indole-3-ethanol and indole-3-pyruvic acid 21 days post-infection. Since IL-22 signaling can also promote barrier repair, we quantified IL-22 transcripts by RT-PCR and found significantly increased levels of IL-22 mRNA in infected mice. These data suggest that Giardia can reduce barrier repair through altered production of AHR ligands by the microbiome, but that IL-22 can counter this effect in some situations. This study will give better insight into developing effective dietary interventions to prevent growth stunting in infected children.
Supported by grant from NIH AI166467