Estrogen signaling suppresses tumor-associated tissue eosinophilia to promote breast tumor growth.

Estrogens regulate eosinophilia in asthma and other inflammatory diseases. Further, peripheral eosinophilia and tumor-associated tissue eosinophilia (TATE) predicts a better response to immune checkpoint blockade (ICB) in breast cancer. However, how and if estrogens affect eosinophil biology in tumors and how this influences ICB efficacy has not been determined. Here, we report that estrogens decrease the number of peripheral eosinophils and TATE, and this contributes to increased tumor growth in validated murine models of breast cancer and melanoma. Moreover, estrogen signaling in healthy female mice also suppressed peripheral eosinophil prevalence by decreasing the proliferation and survival of maturing eosinophils. Inhibiting estrogen receptor (ER) signaling decreased tumor growth in an eosinophil-dependent manner. Further, the efficacy of ICBs was increased when administered in combination with anti-estrogens. These findings highlight the importance of ER signaling as a regulator of eosinophil biology and TATE and highlight the potential near-term clinical application of ER modulators to increase ICB efficacy in multiple tumor types.

Factors influencing nurses' satisfaction to online learning approach: a cross ICU analysis.

BACKGROUND: Given the increasing complexity of illnesses and rapid pace of technological advancements in professional training, it is vital to offer nurses ample opportunities to hone their clinical expertise and skills, particularly in ensuring the delivery of premier medical care. This study aimed to determine the factors and predictors influencing nurses' satisfaction with adopting mobile learning approaches in intensive care unit healthcare settings. Additionally, it sought to investigate the applicability of the technology acceptance model in explaining their inclinations and validating the measurement scales employed in the research. METHODS: The study employed a cross-sectional survey research design, utilizing a technology acceptance questionnaire and a learning satisfaction questionnaire. The survey was conducted in six intensive care unit departments. A total of 212 participants completed the survey as the primary instrument. Rigorous assessments were conducted to establish the content validity and ensure instrument reliability. RESULTS: The findings demonstrated that perceived usefulness was the most influential factor affecting nurses' intentions to embrace mobile learning approaches, with perceived ease of use emerging as the principal determinant of perceived usefulness. CONCLUSIONS: Incorporating mobile learning methodologies is paramount to increasing the calibration of professional nursing education programs. By effectively integrating digital information technology and tools, nursing educators can overcome teaching challenges, deliver innovative clinical nursing education content through mobile learning approaches, and foster optimal development in the field.

Effects of game-based learning integrated with the self-regulated learning strategy on nursing students' entrustable professional activities: A quasi-experimental study.

BACKGROUND: In the field of nursing education, the expertise and knowledge required to perform Leopold's Maneuvers are critical, forming an integral part of Entrustable Professional Activities for nursing students. As a result, mastering Leopold's Maneuvers has become a core component of nursing education. Despite this, the prevailing didactic methods in many nursing courses tend to limit interactive and contextual learning experiences, which can hinder students' ability to engage deeply with the subject matter. This lack of engagement may subsequently affect both the effectiveness of students' learning and students' clinical judgment capacity, essential elements in the competencies of Entrustable Professional Activities. METHODS: A quasi-experimental design was employed in this study, involving a total of 55 nursing university students, with 28 participants in the experimental group and 27 in the control group. The research incorporated game-based learning integrated with the self-regulated learning strategy, and employed a pretest, posttest, and questionnaires to assess students' learning performance, self-efficacy, and learning motivation. The experimental group participated in game-based learning with the self-regulated learning strategy, whereas the control group experienced game-based learning without the integration of self-regulated learning. Learning performance was analyzed using an independent samples t-test, while Analysis of Covariance was employed to compare the self-efficacy and learning motivation of the two groups. RESULTS: The findings showed that the integration of game-based learning with the self-regulated learning strategy can significantly improve students' learning performance, self-efficacy, and learning motivation. CONCLUSION: As an integral part of Entrustable Professional Activities, Leopold's Maneuvers were integrated into an interactive game-based learning environment, coupled with the self-regulated learning strategy in nursing education. This approach aimed at cultivating core competencies among nursing students. This study has demonstrated its efficacy in engaging students effectively, serving as a dynamic resource for immersive learning in Leopold's Maneuvers, aligning well with the design considerations for promoting Entrustable Professional Activities in nursing education.

Root caries in older adults: A co-citation network analysis (1980-2023).

BACKGROUND: Root caries affect the oral health and quality of life of older adults. This study examines the breadth of global research on this topic, aiming to clarify its expansive scope and to shed light on pertinent trends for new researchers in the field. OBJECTIVE: To identify key advances in root caries research as highlighted in high-quality articles from the Social Science Citation Index (SSCI) as well as to explore emerging trends and perspectives. MATERIALS AND METHODS: Using the Web of Science (WoS) database, we conducted a comprehensive review of articles related to root caries in older adults. Our focus was on finding high-quality SSCI articles, identifying major contributors, journals and research trends and exploring areas such as dentistry, oral surgery and medicine for potential future research. RESULTS: Our analysis included 192 articles, each of which was subjected to bibliometric and VOS viewer evaluations. The results revealed a concentration of studies in dentistry, oral surgery and medicine, with gaps identified in areas like anthropology, biochemistry, molecular biology and chemistry. A notable deficiency was found in root caries management. CONCLUSION: We discuss research gaps and propose future directions based on our findings, emphasising interdisciplinary research approaches.

The Effects of Light Therapy on Sleep, Depression, Neuropsychiatric Behaviors, and Cognition Among People Living With Dementia: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Alterations in the suprachiasmatic nucleus due to underlying pathologies disrupt the circadian rhythms in people living with dementia (PLWD). Circadian rhythms significantly impact sleep, emotional, and cognitive functions, with its synchronization depending on light exposure. We performed a meta-analysis to evaluate the effects of light therapy on sleep, depression, neuropsychiatric behaviors, and cognition among PLWD. METHODS: A systematic search was conducted in Cochrane, ClinicalTrials.gov, Embase, EBSCOhost, Ovid-MEDLINE, PubMed, Scopus, Web of Science, and CINAHL databases. The pooled effect size was calculated using the Hedges' g with random-effects model adopted in comprehensive meta-analysis software. The Cochrane risk of bias (RoB 2.0) tool evaluated the quality of studies, while Cochrane's Q and I² tests assessed heterogeneity. RESULTS: A total of 24 studies with 1,074 participants were included. Light therapy demonstrated small-to-medium effects on improving sleep parameters: total sleep time (Hedges' g = 0.19), wake after sleep onset (Hedges' g = 0.24), sleep efficiency (Hedges' g = 0.31), sleep latency (Hedges' g = 0.35), circadian rhythm (acrophase: Hedges' g = 0.36; amplitude: Hedges' g = 0.43), number of night awakenings (Hedges' g = 0.37), sleep disturbance (Hedges'g = 0.45), and sleep quality (Hedges' g = 0.60). Light therapy showed small-to-medium effect on reducing depression (Hedges' g = -0.46) with medium-to-large effect on cyclical function (Hedges' g = -0.68) and mood-related signs and symptoms (Hedges' g = -0.84) subscales. Light therapy also demonstrated small effect on reducing neuropsychiatric behaviors (Hedges' g = -0.34) with medium-to-large effect on agitation (Hedges' g = -0.65), affective symptom (Hedges' g = -0.70), psychosis (Hedges' g = -0.72), and melancholic behavior (Hedges' g = -0.91) subscales. Additionally, light therapy also improved cognition (Hedges' g = 0.39). CONCLUSION: Light therapy could be used as a supportive therapy to improve sleep, depression, cognition, and neuropsychiatric behaviors among PLWD.

Meta-analysis and moderator analysis of the prevalence of malnutrition and malnutrition risk among older adults with dementia.

BACKGROUND: Aging and dementia are common and closely related health problems in older adults, affecting their ability to maintain a healthy diet and ultimately resulting in malnutrition. OBJECTIVE: In this study, we estimated the global prevalence of malnutrition and malnutrition risk in older adults with dementia. DESIGN: Meta-analysis. DATA SOURCES: Embase, Ovid MEDLINE, PubMed, CINAHL, Scopus, and Web of Science were comprehensively searched for articles published from database inception to October 2022. METHODS: Pooled prevalence analysis was conducted using a generalized linear mixed model and a random-effects model. I2 and Cochran's Q statistics were used for identifying heterogeneity. Publication bias was evaluated using Peters' regression test and a funnel plot. Moderator analyses were conducted to investigate variations in the prevalence estimates of the included studies. All statistical analyses were conducted using R software. RESULTS: A total of 16 studies involving a total of 6513 older adults with dementia were included in the analysis. The results indicated that 32.52 % (95 % confidence interval: 19.55-45.49) of all included older adults with dementia had malnutrition, whereas 46.80 % (95 % confidence interval: 38.90-54.70) had a risk of malnutrition. The prevalence of malnutrition was found to be high among older patients living in institutionalized settings (46.59 %) and those with Alzheimer's disease (12.26 %). The factors moderating the prevalence of malnutrition included adequate vitamin B12 consumption, risk behaviors, medical comorbidities, and certain neuropsychiatric symptoms. The prevalence of malnutrition risk was high among women (29.84 %) and patients with Alzheimer's disease (26.29 %). The factors moderating the prevalence of malnutrition risk included total cholesterol level, vitamin B12 consumption, risk behaviors, medical comorbidities, and certain neuropsychiatric symptoms. CONCLUSIONS: Approximately one-third of older adults with dementia are malnourished and nearly half of older adults are at a risk of malnutrition. Encouraging collaboration among health-care professionals and ensuring early assessment and effective management of malnutrition are crucial for maintaining a favorable nutritional status in older adults with dementia. REGISTRATION: This study was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022369329). TWEETABLE ABSTRACT: Globally, approximately 32.52 % of older adults with dementia are malnourished and approximately 46.80 % are at a risk of malnutrition.

Exploring knowledge, attitude, and intention towards advance care planning, advance directive, and the patient self-determination act among hemodialysis patients.

BACKGROUND: Hemodialysis holds the highest incidence and prevalence rate in Taiwan globally. However, the implementation of advance care planning (ACP), advance directives (AD), and patient self-determination acts (PSDA) remains limited. Our objective was to examine the current status of ACP, AD and PSDA and potential opportunities for enhancement. METHODS: We developed a novel questionnaire to assess individuals' knowledge, attitudes, and intentions regarding ACP, AD, and PSDA. We also collected baseline characteristics and additional inquiries for correlation analysis to identify potential factors. Student's t-test and Analysis of Variance were employed to assess significance. RESULTS: Initially, a cohort of 241 patients was initially considered for inclusion in this study. Subsequently, 135 patients agreed to participate in the questionnaire study, resulting in 129 valid questionnaires. Among these respondents, 76 were male (59.9%), and 53 were female (41.1%). Only 13.2% had signed AD. A significant portion (85.3%) indicated that they had not discussed their dialysis prognosis with healthcare providers. Additionally, a mere 14% engaged in conversations about life-threatening decisions. Ninety percent believed that healthcare providers had not furnished information about ACP, and only 30% had discussed such choices with their families. The findings revealed that the average standardized score for ACP and AD goals was 84.97, while the attitude towards PSDA received a standardized score of 69.94. The intention score stood at 69.52 in standardized terms. Potential candidates for ACP initiation included individuals aged 50 to 64, possessing at least a college education, being unmarried, and having no history of diabetes. CONCLUSION: Patients undergoing hemodialysis exhibited a significant knowledge gap concerning ACP, AD, and the PSDA. Notably, a substantial number of dialytic patients had not received adequate information on these subjects. Nevertheless, they displayed a positive attitude, and a considerable proportion expressed a willingness to sign AD. It is imperative for nephrologists to take an active role in initiating ACP discussions with patients from the very beginning.

Facilitating undergraduate students' problem-solving and critical thinking competence via online escape room learning.

AIMS: This study aimed to identify the efficiency of escape room activities in terms of enhancing nursing students' retention of maternity-related knowledge and their overall learning performance. BACKGROUND: Novel teaching methods have been explored as alternatives to traditional approaches. One such strategy is the implementation of escape-room-based techniques, which have been used as an inventive educational approach in nursing. However, there is limited information available on specific applications, such as in maternity education. DESIGN: The study conducted a quasi-experimental design during two semesters of an academic year (i.e., the 2021-2022 academic year). The study was conducted at a university, with participants enrolled in a maternity course. METHODS: The experimental group engaged in an online game-based escape room learning activity during the pregnancy assessment session of their maternity course, while the control group learned with a traditional teaching approach. The Mann-Whitney U test was used to compare the performances of the two groups. RESULTS: Findings from the experimental group suggested that incorporating an online game-based escape room approach into the learning process enhanced students' learning performance, problem-solving skills and critical thinking skills. Additionally, students expressed a consensus that learning through the online game-based escape room approach added enjoyment to the learning experience. CONCLUSIONS: Maternity escape rooms" emerged as an online game-based approach that effectively stimulated nursing students and can serve as a practical resource for engaging in maternity care learning.

Enhanced skin neocollagenesis through the transdermal delivery of poly-L-lactic acid microparticles by using a needle-free supersonic atomizer.

In this study, a spindle-type nozzle was designed to accelerate poly-L-lactic acid (PLLA) microparticles to supersonic velocities for the transdermal delivery of these microparticles to rats. This approach is needle- and pain-free and enhances skin collagen regeneration. The addition of PLLA microparticles at a concentration of 2 mg/mL did not hinder the growth of 3 T3 fibroblasts and Raw264.7 macrophages. The TNF-α assay revealed no obvious inflammation effect of PLLA microparticles at a concentration of 1 mg/mL. A time-lapse recording revealed that after being cocultured with PLLA microparticles for 24 h, Raw264.7 macrophages gradually approached and surrounded the PLLA microparticles. When 3 T3 fibroblasts were cocultured with Raw264.7 macrophages, which were stimulated using PLLA microparticles, collagen synthesis was increased by approximately 60 % compared with that in samples without PLLA microparticles. In vivo animal experiments indicated that after the transdermal delivery of 10 shots of PLLA microparticles through the supersonic atomizer, no obvious changes or damage to the back skin of Sprague-Dawley rats was observed. More importantly, numerous PLLA microparticles penetrated the rat epidermis into the dermal layer. We found macrophages and fibroblasts present close to the PLLA microparticles. Moreover, only mild or no inflammation reaction was observed. Masson staining revealed that after 6-week implantation, 6 % and 12 % of PLLA microparticles significantly stimulated collagen regeneration in 6-week-old and 32-week-old rats. In addition, picrosirius red staining revealed a significant increase in collagen regeneration, especially for type III collagen, following the 6-week implantation of PLLA microparticles. In summary, this study demonstrated an easy, pain-free, nondestructive approach for introducing PLLA microparticles into the dermal layer by using a supersonic atomizer to stimulate collagen regeneration in vivo.

Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress Cancer Metastasis.

Triple-negative breast cancers (TNBC) tend to become invasive and metastatic at early stages in their development. Despite some treatment successes in early-stage localized TNBC, the rate of distant recurrence remains high, and long-term survival outcomes remain poor. In a search for new therapeutic targets for this disease, we observed that elevated expression of the serine/threonine kinase calcium/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) is highly correlated with tumor invasiveness. In validation studies, genetic disruption of CaMKK2 expression or inhibition of its activity with small molecule inhibitors disrupted spontaneous metastatic outgrowth from primary tumors in murine xenograft models of TNBC. High-grade serous ovarian cancer (HGSOC), a high-risk, poor prognosis ovarian cancer subtype, shares many features with TNBC, and CaMKK2 inhibition effectively blocked metastatic progression in a validated xenograft model of this disease. Mechanistically, CaMKK2 increased the expression of the phosphodiesterase PDE1A, which hydrolyzed cyclic guanosine monophosphate (cGMP) to decrease the cGMP-dependent activity of protein kinase G1 (PKG1). Inhibition of PKG1 resulted in decreased phosphorylation of vasodilator-stimulated phosphoprotein (VASP), which in its hypophosphorylated state binds to and regulates F-actin assembly to facilitate cell movement. Together, these findings establish a targetable CaMKK2-PDE1A-PKG1-VASP signaling pathway that controls cancer cell motility and metastasis by impacting the actin cytoskeleton. Furthermore, it identifies CaMKK2 as a potential therapeutic target that can be exploited to restrict tumor invasiveness in patients diagnosed with early-stage TNBC or localized HGSOC. SIGNIFICANCE: CaMKK2 regulates actin cytoskeletal dynamics to promote tumor invasiveness and can be inhibited to suppress metastasis of breast and ovarian cancer, indicating CaMKK2 inhibition as a therapeutic strategy to arrest disease progression.

The effect of cognitive training on domains of attention in older adults with mild cognitive impairment and mild dementia: A meta-analysis of randomised controlled trials.

Background: Attention is essential to daily life and cognitive functioning, and attention deficits can affect daily functional and social behaviour, such as falls, risky driving, and accidental injuries. However, attention function is important yet easily overlooked in older adults with mild cognitive impairment, and evidence is limited. We aimed to explore the pooled effect of cognitive training on domains of attention in older adults with mild cognitive impairment and mild dementia using a meta-analysis of randomised controlled trials. Methods: We searched PubMed, Embase, Scopus, Web of Science, CINAHL, PsycINFO, and Cochrane Library for randomised controlled trials (RCTs) up to 3 November 2022. We included participants aged ≥50 years diagnosed with cognitive impairment, with various cognitive training interventions as the intervention measures. The primary outcome was overall attention and the secondary outcomes were attention in different domains and global cognitive function. We calculated the Hedges' g and confidence intervals (CIs) using a random-effects model to evaluate the effect size of the outcome measures and evaluated heterogeneity using the χ2 test and I2 value. Results: We included 17 RCTs and found that cognitive training interventions improve overall attention (Hedges' g = 0.41; 95% CI = 0.13, 0.70), selective attention (Hedges' g = 0.37; 95% CI = 0.19, 0.55), divided attention (Hedges' g = 0.38; 95% CI = 0.03, 0.72), and global cognitive function (Hedges' g = 0.30; 95% CI = 0.02, 0.58) in older adults with mild cognitive impairment, but with relatively low effectiveness. Conclusions: Cognitive training intervention can improve some attention functions in older adults with mild cognitive impairment. Attention function training should also be incorporated into routine activities and long-term sustainability planning to delay the deterioration of attention function in older adults. Besides reducing their risk of abnormal events in daily life (such as falls), it can also improve their quality of life and help reduce the progression of cognitive impairment, achieving early detection of secondary prevention. Registration: PROSPERO (CRD42022385211).

Ca 2+ /Calmodulin Dependent Protein Kinase Kinase-2 (CaMKK2) promotes Protein Kinase G (PKG)-dependent actin cytoskeletal assembly to increase tumor metastasis.

Triple-negative breast cancers (TNBCs) tend to become highly invasive early during cancer development. Despite some successes in the initial treatment of patients diagnosed with early-stage localized TNBC, the rate of metastatic recurrence remains high with poor long-term survival outcomes. Here we show that elevated expression of the serine/threonine-kinase, Calcium/Calmodulin (CaM)-dependent protein kinase kinase-2 (CaMKK2), is highly correlated with tumor invasiveness. We determined that genetic disruption of CaMKK2 expression, or inhibition of its activity, disrupted spontaneous metastatic outgrowth from primary tumors in murine xenograft models of TNBC. High-grade serous ovarian cancer (HGSOC), a high-risk, poor-prognosis ovarian cancer subtype, shares many genetic features with TNBC, and importantly, CaMKK2 inhibition effectively blocked metastatic progression in a validated xenograft model of this disease. Probing the mechanistic links between CaMKK2 and metastasis we defined the elements of a new signaling pathway that impacts actin cytoskeletal dynamics in a manner which increases cell migration/invasion and metastasis. Notably, CaMKK2 increases the expression of the phosphodiesterase PDE1A which decreases the cGMP-dependent activity of protein kinase G1 (PKG1). This inhibition of PKG1 results in decreased phosphorylation of Vasodilator-Stimulated Phosphoprotein (VASP), which in its hypophosphorylated state binds to and regulates F-actin assembly to facilitate contraction/cell movement. Together, these data establish a targetable CaMKK2-PDE1A-PKG1-VASP signaling pathway that controls cancer cell motility and metastasis. Further, it credentials CaMKK2 as a therapeutic target that can be exploited in the discovery of agents for use in the neoadjuvant/adjuvant setting to restrict tumor invasiveness in patients diagnosed with early-stage TNBC or localized HGSOC.

Global prevalence of low resilience among the general population and health professionals during the COVID-19 pandemic: A meta-analysis.

OBJECTIVE: To estimate the global prevalence of low resilience among the general population and health professionals during the COVID-19 pandemic. METHODS: Embase, Ovid-MEDLINE, PubMed, Scopus, Web of Science, CINAHL, WHO COVID-19 databases, and grey literature were searched for studies from January 1, 2020, to August 22, 2022. Hoy's assessment tool was used to assess for risk of bias. Meta-analysis and moderator analysis was performed using the Generalized Linear Mixed Model with a corresponding 95 % confidence interval (95 % CI) adopting the random-effect model in R software. Between-study heterogeneity was measured using I2 and τ2 statistics. RESULTS: Overall, 44 studies involving 51,119 participants were identified. The pooled prevalence of low resilience was 27.0 % (95 % CI: 21.0 %-33.0 %) with prevalence among the general population being 35.0 % (95 % CI: 28.0 %-42.0 %) followed by 23.0 % (95 % CI: 16.0 %-30.9 %) for health professionals. The 3-month trend analysis of the prevalence of low resilience beginning January 2020 to June 2021 revealed upward then downward patterns among overall populations. The prevalence of low resilience was higher in females, studied during the delta variant dominant period, frontline health professionals, and undergraduate degree education. LIMITATIONS: Study outcomes showed high heterogeneity; however, sub-group and meta-regression analyses were conducted to identify potential moderating factors. CONCLUSIONS: Globally, 1 out of 4 people among the general population and health professionals experienced low resilience due to COVID-19 adversity. The prevalence of low resilience was twice as much among the general population compared to health professionals. These findings provide information for policymakers and clinicians in the development and implementation of resilience-enhancing programs.

Effects of a Technology-Supported Decision, Reflection, and Interaction Approach on Nursing Students' Learning Achievement and Self-Efficacy in Professional Training: A Pilot Study.

In professional training, it is important to provide students with opportunities to make judgments on practical cases. However, most training courses are conducted in a one-to-many teaching mode, and it is not easy to consider the needs of individual students. In this study, a technology-supported Decision, Reflection, and Interaction (DRI)-based professional training approach is proposed to cope with this problem for those courses aiming at fostering students' competence in making correct judgments when facing real cases. To verify the effectiveness of the proposed method, an experiment was conducted. Two classes of 38 students from a nursing school were the participants. One class was an experimental group using the DRI-based professional training approach, and the other class was the control group using the conventional technology-assisted training approach. The experimental results showed that applying the proposed approach significantly improved the students' learning achievement and self-efficacy more than the conventional technology-assisted approach. In addition, based on the interview results, the students generally believed that learning through the DRI-based professional training approach benefited them from several perspectives, including "increasing the value of activities", "enhancing the planning and expensive capacity of conspicuous approaches", "promoting decision-making", "improving learning reflection", and "providing students with personalized interaction".

Prevalence of grief symptoms and disorders in the time of COVID-19 pandemic: A meta-analysis.

Millions of people worldwide are mourning the loss of loved ones due to the COVID-19 epidemic, which may adversely impact their mental health. This meta-analysis aimed to investigate pandemic grief symptoms and disorders for developing policy, practice, and research priorities. The databases of Cochrane, Embase, Ovid-MEDLINE, WHO COVID-19, NCBI SARS-CoV-2, Scopus, Web of Science, CINAHL, and Science Direct were comprehensively searched until July 31, 2022. The Joanna Briggs Institute's and Hoy's criteria were used to evaluate the studies. A pooled prevalence was presented in a forest plot figure with a corresponding 95% confidence interval (CI) and prediction interval. Between-study heterogeneity was measured using the I2 and Q statistics. Variations in the prevalence estimates in different subgroups were examined by moderator meta-analysis. The search identified 3677 citations, of which 15 studies involving 9289 participants were included in the meta-analysis. The pooled prevalence rate of grief symptoms was 45.1% (95%CI: 32.6%-57.5%), and grief disorder was 46.4% (95%CI: 37.4%-55.5%). Grief symptoms were significantly higher in <6 months (45.8%; 95%CI: 26.3%-65.3%) compared to the period of more than 6 months. Unfortunately, moderator analyses for grief disorders could not be performed due to limited studies. The prevalence of grief problems during the pandemic was substantially higher than in non-pandemic conditions; therefore, it is crucial to strengthen bereavement support to reduce psychological distress. The results provide a foundation for nurses and healthcare workers to anticipate a heightened need for support and provision of bereavement care in the post-pandemic era.

Effects of robot-assisted digital storytelling on hospitalized children's communication during the COVID-19 pandemic.

This study proposed a robot-assisted digital storytelling approach to reduce hospitalized children's anxiety about intravenous injections and to improve their therapeutic communication and therapeutic engagement. In order to verify the effectiveness of the robot-assisted digital storytelling approach, a randomized controlled study was implemented. A total of 47 children from a regional hospital were randomly assigned to an experimental group (n = 21) and a control group (n = 26). The experimental group adopted the robot-assisted digital storytelling approach in health education for intravenous injections, while the control group received video-based health education. The study results indicated that the proposed robot-assisted digital storytelling approach not only reduced the children's anxiety, but also had positive effects on children's communication about intravenous injections, emotions during hospitalization, and therapeutic engagement. As a consequence, it is suggested that educators and researchers consider adopting robot-assisted digital storytelling to facilitate nursing clinical health education for children.

Fatigue During Pregnancy: A Bibliometric Analysis.

OBJECTIVE: This study uses a systematic review with bibliometric analysis methods to investigate the characteristics of the most cited research papers in the field of nursing fatigue and pregnancy. METHODS: In the Web of Science (WoS) database. We used the keywords "fatigue" and "pregnancy" to search for articles published from 2000 to 2020, limited to SSCI and Science Citation Index (SCI) journal-type articles. This study identifies the most cited studies in the WoS database based on PRISMA guidelines (Preferred reporting items for systematic reviews and meta-analyses). These studies form the research data, then visualized and analyzed using a retrospective bibliometric analysis and VOSviewer. RESULTS: The studies in the dataset were analyzed in 319 different journals in 51 countries between 2000 and 2020. The study was found that the United States (US) was the country with the highest yield. The most frequent keywords were postpartum, depression, sleep, and postpartum depression. CONCLUSION: The research results further laid the foundation of bibliometrics for scholars and identified researchers, scientific journals, countries, and hot topics for fatigue-related pregnancy literature. Journals with high impact factors contain the most cited research and open new horizons for research in the nursing field of pregnancy-related fatigue, thus providing research inspiration for investigators in this field.

Eosinophilia in cancer and its regulation by sex hormones.

Gender differences in the functionality of the immune system have been attributed, in part, to direct and indirect effects of sex steroids, especially estrogens, on immune cell repertoire and activity. Notable are studies that have defined roles for estrogens in the regulation of the biology of dendritic cells (DCs), macrophages, T cells and natural killer (NK) cells. Although estrogens can modulate eosinophil function, the mechanisms by which this occurs and how it contributes to the pathobiology of different diseases remains underexplored. Furthermore, although the importance of eosinophils in infection is well established, it remains unclear as to how these innate immune cells, which are present in different tumors, impact the biology of cancer cells and/or response to therapeutics. The observation that eosinophilia influences the efficacy of immune checkpoint blockers (ICBs) is significant considering the role of estrogens as regulators of eosinophil function and recent studies suggesting that response to ICBs is impacted by gender. Thus, in this review, we consider what is known about the roles of estrogen(s) in regulating tissue eosinophilia/eosinophil function and how this influences the pathobiology of breast cancer (in particular). This information provides the context for a discussion of how estrogens/the estrogen receptor (ER) signaling axis can be targeted in eosinophils and how this would be expected to influence the activity of standard-of-care interventions and contemporary immunotherapy regimens in cancer(s).

Increased CaMKK2 Expression Is an Adaptive Response That Maintains the Fitness of Tumor-Infiltrating Natural Killer Cells.

Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a key regulator of energy homeostasis in several cell types. Expression of this enzyme in tumor cells promotes proliferation and migration, and expression in tumor-associated immune cells facilitates M2 macrophage polarization and the development of myeloid-derived suppressor cells. Thus, there has been interest in developing CaMKK2 inhibitors as potential anticancer therapeutics. One impediment to clinical development of these agents is that the roles of CaMKK2 in other cellular compartments within the tumor immune microenvironment remain to be established. We report herein that CaMKK2 is expressed at low basal levels in natural killer (NK) cells but is upregulated in tumor-infiltrating NK cells where it suppresses apoptosis and promotes proliferation. NK cell-intrinsic deletion of CaMKK2 increased metastatic progression in several murine models, establishing a critical role for this enzyme in NK cell-mediated antitumor immunity. Ablation of the CaMKK2 protein, but not inhibition of its kinase activity, resulted in decreased NK-cell survival. These results indicate an important scaffolding function for CaMKK2 in NK cells and suggest that competitive CaMKK2 inhibitors and ligand-directed degraders (LDD) are likely to have distinct therapeutic utilities. Finally, we determined that intracellular lactic acid is a key driver of CaMKK2 expression, suggesting that upregulated expression of this enzyme is an adaptive mechanism by which tumor-infiltrating NK cells mitigate the deleterious effects of a lactic acid-rich tumor microenvironment. The findings of this study should inform strategies to manipulate the CaMKK2-signaling axis as a therapeutic approach in cancer.

Estrogen Receptor Signaling in the Immune System.

The immune system functions in a sexually dimorphic manner, with females exhibiting more robust immune responses than males. However, how female sex hormones affect immune function in normal homeostasis and in autoimmunity is poorly understood. In this review, we discuss how estrogens affect innate and adaptive immune cell activity and how dysregulation of estrogen signaling underlies the pathobiology of some autoimmune diseases and cancers. The potential roles of the major circulating estrogens, and each of the 3 estrogen receptors (ERα, ERß, and G-protein coupled receptor) in the regulation of the activity of different immune cells are considered. This provides the framework for a discussion of the impact of ER modulators (aromatase inhibitors, selective estrogen receptor modulators, and selective estrogen receptor downregulators) on immunity. Synthesis of this information is timely given the considerable interest of late in defining the mechanistic basis of sex-biased responses/outcomes in patients with different cancers treated with immune checkpoint blockade. It will also be instructive with respect to the further development of ER modulators that modulate immunity in a therapeutically useful manner.