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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. In this study, we estimated the global prevalence of malnutrition and malnutrition risk in older adults with dementia. Meta-analysis. Embase, Ovid MEDLINE, PubMed, CINAHL, Scopus, and Web of Science were comprehensively searched for articles published from database inception to October 2022. Pooled prevalence analysis was conducted using a generalized linear mixed model and a random-effects model. I 2 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. 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 B 12 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 B 12 consumption, risk behaviors, medical comorbidities, and certain neuropsychiatric symptoms. 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. This study was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022369329). Globally, approximately 32.52 % of older adults with dementia are malnourished and approximately 46.80 % are at a risk of malnutrition. [ABSTRACT FROM AUTHOR]

Endocrine therapy is often considered as a treatment for hormone-responsive gynecologic malignancies. In breast cancer, activating mutations in the estrogen receptor (mutESR1) contribute to therapeutic resistance to endocrine therapy, especially aromatase inhibitors (AIs). The purpose of this study was to evaluate the frequency and clinical relevance of ESR1 genomic alterations in gynecologic malignancies. DNA from FFPE tumor tissue obtained during routine clinical care for 9645 gynecologic malignancies (ovary, fallopian tube, uterus, cervix, vagina, vulvar, and placenta) was analyzed for all classes of genomic alterations (base substitutions (muts), insertions, deletions, rearrangements, and amplifications) in ESR1 by hybrid capture next generation sequencing. A subset of alterations was characterized in laboratory-based transcription assays for response to endocrine therapies. A total of 295 ESR1 genomic alterations were identified in 285 (3.0%) cases. mutESR1 were present in 86 (0.9%) cases and were more common in uterine compared to other cancers (2.0% vs <1%, respectively p < 0.001). mutESR1 were enriched in carcinomas with endometrioid versus serous histology (4.4% vs 0.2% respectively, p < 0.0001 in uterine and 3.5% vs 0.3% respectively, p = 0.0004 in ovarian carcinomas). In three of four patients with serial sampling, mutESR1 emerged under the selective pressure of AI therapy. Despite decreased potency of estrogen receptor (ER) antagonists in transcriptional assays, clinical benefit was observed following treatment with selective ER-targeted therapy, in one case lasting >48 months. While the prevalence of ESR1 mutations in gynecologic malignancies is low, there are significant clinical implications useful in guiding therapeutic approaches for these cancers. • ESR1 mutations lead to constitutive activation of ERα and resistance to aromatase inhibitors. • A subset of gynecologic malignancies, particularly those with endometrioid histology, harbor ESR1 mutations. • ESR1 mutations may arise in the setting of treatment with AIs, or may be present in the initial tumor. • SERM/SERD therapy has the potential to provide benefit despite the presence of an ESR1 mutation. [ABSTRACT FROM AUTHOR]

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., (© 2024. The Author(s).)

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., Competing Interests: Declaration of competing interest Authors declare no conflicts of interest associated with this research., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., Competing Interests: DISCLOSURES The authors declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article. The authors received no financial support for the research, authorship, or publication of this article., (Copyright © 2023 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

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., (© 2024 Gerodontology Association and John Wiley & Sons Ltd.)

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., (© 2023. The Author(s).)

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., Competing Interests: Declaration of competing interest The authors have no conflicts to disclose., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The author would like to declare that there is no conflict of interest in this study. We declare that this manuscript is original, has not been published before, and is not currently being considered for publication elsewhere. No conflicts of interest are associated with this publication, and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., (©2023 The Authors; Published by the American Association for Cancer Research.)

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 χ 2 test and I 2 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)., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2023 by the Journal of Global Health. All rights reserved.)

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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".

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., Competing Interests: Conflict of interestThe authors declare no conflicts of interest associated with this research., (© Association for Educational Communications and Technology 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

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., (©2022 American Association for Cancer Research.)

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)., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Immune checkpoint blockade (ICB) therapies have significantly prolonged patient survival across multiple tumor types, particularly in melanoma. Interestingly, sex-specific differences in response to ICB have been observed, with males receiving a greater benefit from ICB than females, although the mechanism or mechanisms underlying this difference are unknown. Mining published transcriptomic data sets, we determined that the response to ICBs is influenced by the functionality of intratumoral macrophages. This puts into context our observation that estrogens (E2) working through the estrogen receptor α (ERα) stimulated melanoma growth in murine models by skewing macrophage polarization toward an immune-suppressive state that promoted CD8+ T cell dysfunction and exhaustion and ICB resistance. This activity was not evident in mice harboring macrophage-specific depletion of ERα, confirming a direct role for estrogen signaling within myeloid cells in establishing an immunosuppressed state. Inhibition of ERα using fulvestrant, a selective estrogen receptor downregulator (SERD), decreased tumor growth, stimulated adaptive immunity, and increased the antitumor efficacy of ICBs. Further, a gene signature that determines ER activity in macrophages predicted survival in patients with melanoma treated with ICB. These results highlight the importance of E2/ER signaling as a regulator of intratumoral macrophage polarization, an activity that can be therapeutically targeted to reverse immune suppression and increase ICB efficacy.

Hypercholesterolemia and dyslipidemia are associated with an increased risk for many cancer types and with poor outcomes in patients with established disease. Whereas the mechanisms by which this occurs are multifactorial we determine that chronic exposure of cells to 27-hydroxycholesterol (27HC), an abundant circulating cholesterol metabolite, selects for cells that exhibit increased cellular uptake and/or lipid biosynthesis. These cells exhibit substantially increased tumorigenic and metastatic capacity. Notably, the metabolic stress imposed upon cells by the accumulated lipids requires sustained expression of GPX4, a negative regulator of ferroptotic cell death. We show that resistance to ferroptosis is a feature of metastatic cells and further demonstrate that GPX4 knockdown attenuates the enhanced tumorigenic and metastatic activity of 27HC resistant cells. These findings highlight the general importance of ferroptosis in tumor growth and metastasis and suggest that dyslipidemia/hypercholesterolemia impacts cancer pathogenesis by selecting for cells that are resistant to ferroptotic cell death., (© 2021. The Author(s).)

Students who learn evidence-based nursing can assist the healthcare team to make proper medical decisions and provide patients with valuable advice, thus optimizing the quality of patient care in specific situations. In clinical work, nursing staff members participate in decision making by searching for relevant empirical nursing literature, a basic ability required to enter clinical practice. In traditional instruction, nursing students are taught the Problem, Intervention, Comparison, and Outcome method to learn to use library resources and gather empirical nursing knowledge for decision making. However, it is a challenge for most students to have sufficient practice to make decisions correctly and to have opportunities to perceive medical cases from diverse perspectives. Therefore, we propose a peer assessment-based Problem, Intervention, Comparison, and Outcome approach to help nursing students locate correct evidence and make appropriate decisions about patient care. We performed an experiment with our approach in a nursing university training program. The experimental results reveal that the subjects learning with the proposed approach show better evidence-based nursing knowledge, learning attitude, and critical thinking ability than those learning with the traditional approach., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Tumor-associated myeloid cells regulate tumor growth and metastasis, and their accumulation is a negative prognostic factor for breast cancer. Here we find calcium/calmodulin-dependent kinase kinase (CaMKK2) to be highly expressed within intratumoral myeloid cells in mouse models of breast cancer, and demonstrate that its inhibition within myeloid cells suppresses tumor growth by increasing intratumoral accumulation of effector CD8 + T cells and immune-stimulatory myeloid subsets. Tumor-associated macrophages (TAMs) isolated from Camkk2 -/- mice expressed higher levels of chemokines involved in the recruitment of effector T cells compared to WT. Similarly, in vitro generated Camkk2 -/- macrophages recruit more T cells, and have a reduced capability to suppress T cell proliferation, compared to WT. Treatment with CaMKK2 inhibitors blocks tumor growth in a CD8 + T cell-dependent manner, and facilitates a favorable reprogramming of the immune cell microenvironment. These data, credential CaMKK2 as a myeloid-selective checkpoint, the inhibition of which may have utility in the immunotherapy of breast cancer.

Background: The survival of children with malignant germ cell tumor (GCT) increased over the past 2 decades with platinum-based chemotherapy. This report has three objectives: (1) comparison of PVB (cisplatin, vinblastine, and bleomycin) with JEB (carboplatin, etoposide, and bleomycin) regimens; (2) treatment modality of vaginal GCT; and (3) management of stage I testicular yolk sac tumor (YST) in boys under 2 years old., Methods: From January 1, 1987 to December 31, 2010, 81 patients with malignant extracranial GCT were treated. Two consecutive protocols, PVB followed by JEB, were used. Girls with vaginal YST received minimal surgery and chemotherapy. Boys under 2 years old with Stage I testicular YST received surgery with or without chemotherapy., Results: As of June 30, 2012, the 10-year overall survival (OS) was 95 ± 3% (standard error) and the event-free survival (EFS) was 88 ± 4%. With PVB, 35 patients had 10-year OS of 91 ± 5% and EFS of 89 ± 5%. With JEB, 25 patients had 7-year OS of 96 ± 5% and EFS of 96 ± 5%. All five girls with vaginal YST were cured with vagina-preserved strategy. In 32 boys age under 2 years old with stage I YST, 16 with light chemotherapy were all in EFS, whereas two of 16 patients without chemotherapy relapsed. After PVB, six patients developed nephrotoxicity and one had pulmonary fibrosis., Conclusion: Girls with vaginal YST who received minimal surgery and chemotherapy had excellent prognosis and sexual organs were preservable. Light chemotherapy after surgery is a treatment option for boys under 2 years old with stage I YST to decrease relapse rate. Both JEB and PVB are effective. JEB resulted in more myelosuppression but otherwise less serious long-term toxicity than PVB., (Copyright © 2015. Published by Elsevier B.V.)

Elevated expression of the orphan nuclear receptor estrogen-related receptor α (ERRα) has been associated with a negative outcome in several cancers, although the mechanism(s) by which this receptor influences the pathophysiology of this disease and how its activity is regulated remain unknown. Using a chemical biology approach, it was determined that compounds, previously shown to inhibit canonical Wnt signaling, also inhibited the transcriptional activity of ERRα. The significance of this association was revealed in a series of biochemical and genetic experiments that show that (a) ERRα, β-catenin (β-cat), and lymphoid enhancer-binding factor-1 form macromolecular complexes in cells, (b) ERRα transcriptional activity is enhanced by β-cat expression and vice versa, and (c) there is a high level of overlap among genes previously shown to be regulated by ERRα or β-cat. Furthermore, silencing of ERRα and β-cat expression individually or together dramatically reduced the migratory capacity of breast, prostate, and colon cancer cells in vitro. This increased migration could be attributed to the ERRα/β-cat-dependent induction of WNT11. Specifically, using (a) conditioned medium from cells overexpressing recombinant WNT11 or (b) WNT11 neutralizing antibodies, we were able to show that this protein was the key mediator of the promigratory activities of ERRα/β-cat. Together, these data provide evidence for an autocrine regulatory loop involving transcriptional upregulation of WNT11 by ERRα and β-cat that influences the migratory capacity of cancer cells., (Copyright © 2010 AACR.)

Expression of estrogen-related receptor alpha (ERRalpha) has recently been shown to carry negative prognostic significance in breast and ovarian cancers. The specific role of this orphan nuclear receptor in tumor growth and progression, however, is yet to be fully understood. The significant homology between estrogen receptor alpha (ERalpha) and ERRalpha initially suggested that these receptors may have similar transcriptional targets. Using the well-characterized ERalpha-positive MCF-7 breast cancer cell line, we sought to gain a genome-wide picture of ERalpha-ERRalpha cross-talk using an unbiased microarray approach. In addition to generating a host of novel ERRalpha target genes, this study yielded the surprising result that most ERRalpha-regulated genes are unrelated to estrogen signaling. The relatively small number of genes regulated by both ERalpha and ERRalpha led us to expand our study to the more aggressive and less clinically treatable ERalpha-negative class of breast cancers. In this setting, we found that ERRalpha expression is required for the basal level of expression of many known and novel ERRalpha target genes. Introduction of a small interfering RNA directed to ERRalpha into the highly aggressive breast carcinoma MDA-MB-231 cell line dramatically reduced the migratory potential of these cells. Although stable knockdown of ERRalpha expression in MDA-MB-231 cells had no effect on in vitro cell proliferation, a significant reduction of tumor growth rate was observed when these cells were implanted as xenografts. Our results confirm a role for ERRalpha in breast cancer growth and highlight it as a potential therapeutic target for estrogen receptor-negative breast cancer.

This paper was designed to describe the experience of nurses who applied Gua-Sha, a traditional Asian healing technique, in caring for a parturient woman suffering from breast fullness. The caring period ran from the second day postpartum through the mother's discharge from the hospital, and included telephone follow up during the first and second postpartum weeks. Main caring activities included: (1) supporting and reinforcing the mother's confidence to encourage continued breastfeeding; (2) making sure the baby suckled in a good position and that the mother mastered proper breastfeeding techniques; (3) applying Gua-Sha to help breast milk expression and reduce the breast fullness discomfort; and (4) following up regularly on breastfeeding and breast fullness conditions. As a result, the mother was able to continue breastfeeding and could eventually take care of herself, thus achieving a satisfactory breast feeding experience.

This paper is designed to describe the nursing experiences of applying a birth ball to help a parturient woman in labor, who had experienced labor pains and was accompanied by her husband. On the basis of family-centered nursing, on October 8, 2005, the authors taught, this couple various positions to be adopted using the birth ball to help the woman deliver her baby with minimum pain and to help the husband to accompany his mate in a strong and positive way. In this way, eventually, the woman delivered her baby, safely and smoothly, experiencing the whole process satisfactorily.

The aim of this study was to systematically examine the inhibitory mechanisms of the flavonoid alpha-naphthoflavone (alpha-NF) in platelet activation. In this study, alpha-NF concentration dependently (5-20 microM) inhibited platelet aggregation stimulated by agonists. alpha-NF (5 and 10 microM) inhibited intracellular Ca(2+) mobilization, phosphoinositide breakdown, and thromboxane A(2) formation stimulated by collagen (1 microg/mL) in human platelets. In addition, alpha-NF (5 and 10 microM) markedly increased levels of cyclic GMP and cyclic GMP-induced vasodilator-stimulated phosphoprotein (VASP) Ser(157) phosphorylation. Rapid phosphorylation of a platelet protein of Mr 47,000 (P47), a marker of protein kinase C activation, was triggered by phorbol-12,13-dibutyrate (60 nM). This phosphorylation was markedly inhibited by alpha-NF (5 and 10 microM). However, alpha-NF (5 and 10 microM) did not reduce the electron spin resonance (ESR) signal intensity of hydroxyl radicals in collagen (1 microg/mL)-activated platelets. These results indicate that the antiplatelet activity of alpha-NF may be involved in the following pathways. (1) alpha-NF may inhibit the activation of phospholipase C, followed by inhibition of phosphoinositide breakdown, protein kinase C activation, and thromboxane A(2) formation, thereby leading to inhibition of intracellular Ca(2+) mobilization. (2) alpha-NF also activated the formation of cyclic GMP, resulting in inhibition of platelet aggregation. These results strongly indicate that alpha-NF appears to represent a novel and potent antiplatelet agent for treatment of arterial thromboembolism.

The androgen receptor (AR), a member of the nuclear receptor family, is a ligand-inducible transcription factor. In the prostate gland, androgens regulate the transcription of several genes that ultimately result in cell growth and differentiation. With a goal of developing tissue-selective AR modulators that can be used to treat prostate cancer and other androgenopathies, we have taken an approach to identify androgens that function in a manner distinct from the physiological androgens testosterone and dihydrotestosterone. Classical AR agonists function by binding to and inducing a conformational change in the receptor. This facilitates the obligate interaction of the amino and carboxyl terminus of the receptor, recruitment of coactivators, and subsequent regulation of target genes. On the basis of this paradigm, we screened a library of potential AR agonists for compounds that induce an "activating" conformational change in the receptor structure but that do not facilitate a high-affinity intermolecular interaction between the amino and carboxyl terminus. Compounds identified in this manner behaved as partial agonists of AR-mediated transcription in a variety of assays. Additional compounds were identified in this screen that did not allow the activation function-2 coactivator pocket to form and were demonstrated to function as weak agonists of AR-mediated transcription. Surprisingly, when we examined the ability of these compounds to induce cell proliferation, we observed that despite having different degrees of partial agonist activities on classical transcriptional responses (i.e., induction of prostate-specific antigen), these compounds were as efficacious as dihydrotestosterone in stimulating proliferation. The unexpected finding that AR-mediated transcription and proliferation can be uncoupled suggests that AR is not used in the same manner in all androgen-regulated biological processes.

The term selective estrogen receptor modulators describes a group of pharmaceuticals that function as estrogen receptor (ER) agonists in some tissues but that oppose estrogen action in others. Although the name for this class of drugs has been adopted only recently, the concept is not new, as compounds exhibiting tissue-selective ER agonist/antagonist properties have been around for nearly 40 years. What is new is the idea that it may be possible to capitalize on the paradoxical activities of these drugs and develop them as target organ-selective ER agonists for the treatment of osteoporosis and other estrogenopathies. This realization has provided the impetus for research in this area, the progress of which is discussed in this review.