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Abstract Women with a pathogenic germline mutation in the BRCA1 gene face a very high lifetime risk of developing breast cancer, estimated at 72% by age 80. Prophylactic bilateral mastectomy is the only effective way to lower their risk; however, most women with a mutation opt for intensive screening with annual MRI and mammography. Given that the BRCA1 gene was identified over 20 years ago, there is a need to identify a novel non-surgical approach to hereditary breast cancer prevention. Here, we provide a review of the emerging preclinical and epidemiologic evidence implicating the dysregulation of progesterone-mediated receptor activator of nuclear factor κB (RANK) signaling in the pathogenesis of BRCA1-associated breast cancer. Experimental studies have demonstrated that RANK inhibition suppresses Brca1-mammary tumorigenesis, suggesting a potential target for prevention. Data from studies conducted among women with a BRCA1 mutation further support this pathway in BRCA1-associated breast cancer development. Progesterone-containing (but not estrogen-alone) hormone replacement therapy is associated with an increased risk of breast cancer in women with a BRCA1 mutation. Furthermore, BRCA1 mutation carriers have significantly lower levels of circulating osteoprotegerin (OPG), the decoy receptor for RANK-ligand (RANKL) and thus endogenous inhibitor of RANK signaling. OPG levels may be associated with the risk of disease, suggesting a role of this protein as a potential biomarker of breast cancer risk. This may improve upon current risk prediction models, stratifying women at the highest risk of developing the disease, and further identify those who may be targets for anti-RANKL chemoprevention. Collectively, the evidence supports therapeutic inhibition of the RANK pathway for the primary prevention of BRCA1-associated breast cancer, which may generate unique prevention strategies (without prophylactic surgery) and enhance quality of life.

Objectives: This study aimed to determine whether the olfactory bulb height (OBH) measured using magnetic resonance imaging (MRI) has clinical utility as an imaging biomarker in the evaluation of patients with idiopathic Parkinson's disease (iPD) through its correlation with movement impairment. Methods: This retrospective study included cognitively intact patients with suspected parkinsonism. All participants underwent T2-weighted imaging to measure OBH. Logistic regression was used to determine whether OBH was an independent risk factor for distinguishing iPD patients from disease controls, and its relation with clinical parameters related to motor impairment, including clinical laterality, modified Hoehn and Yahr (HY) stage, and Unified Parkinson's Disease Rating Scale (UPDRS) III score, was investigated. Results: Based on the final clinical diagnosis, 79 patients with iPD and 16 disease controls were included. The mean OBH was significantly smaller in iPD than in disease controls (p < 0.0001). OBH was a significant independent predictor of iPD, with a cutoff of 1.52 mm. In the comparison among the ipsilateral, contralateral side of iPD with clinical laterality, and disease control group, the OBH of the disease control group was significantly larger than both the ipsilateral and contralateral sides (P < 0.05). However, there was no significant difference in OBH between the ipsilateral and contralateral sides (p > 0.05). OBH according to HY stage was significantly smaller in HY stage 2–3 groups than in the disease control group (p < 0.001). The correlation analysis between UPDRS III and OBH showed a mild negative correlation (r = -0.32, p = 0.013). Conclusions: MRI-measured OBH is decreased in iPD regardless of age and sex and may be correlated with the progression of motor symptoms in the iPD. [ABSTRACT FROM AUTHOR]

While invasive success of alien plant species is often attributed to their superior competitive abilities, it is also suggested that competitive ability depends on the target species of competition and resource availability. In addition, it remains unclear whether invaders and co‐occurring plants in the introduced area exhibit distinctive inter‐ and intraspecific competitive intensities. This study aimed to evaluate the competitive ability of a successful invader, Lactuca serriola, through a combination of field surveys and a growth chamber experiment. First, we assessed biodiversity and the biomass of co‐occurring plants in both L. serriola‐invaded and uninvaded plots across nine sites in South Korea. Subsequently, a pairwise competition experiment was conducted between L. serriola and three weedy plant species commonly found in the invaded plots, Chenopodium album, Erigeron canadensis, and Oenothera biennis, under differential nutrient levels. Diversity indices of plant communities and the biomass of most co‐occurring plants showed no significant difference between invaded and uninvaded plots. L. serriola and testing weedy plants exhibited mutually negative effects on biomass when grown together in the same pot, with the intensity of interspecific competition being comparable across nutrient treatments. Notably, intraspecific competition of L. serriola was weaker than testing weedy plants, particularly manifest in the high‐nutrient treatment. The results of both field and growth‐chamber studies demonstrated that L. serriola was not a particularly strong competitor compared to its neighboring weedy plants. Its successful invasion can be partially attributed to its weak intraspecific competition intensity, which potentially facilitate successful establishment with high density. [ABSTRACT FROM AUTHOR]

Simple Summary: Epstein–Barr virus-associated gastric carcinoma (EBVaGC) is a type of stomach cancer linked to EBV infection. This study explores how the male hormone dihydrotestosterone (DHT) affects the immune response against EBVaGC. Using the SNU719 cell line, we treated the cells with DHT and observed an increased expression of the androgen receptor (AR) and the activation of the NF-κB pathway. This led to higher levels of MICA, a protein that interacts with immune cells like natural killer (NK) and T cells, enhancing their ability to kill EBVaGC cells. Importantly, this immune boost occurred without increasing harmful inflammatory signals. Our findings suggest that DHT enhances the immune system's ability to target EBVaGC, providing a potential therapeutic approach by modulating androgen signaling to improve anti-tumor immunity. Background: Epstein–Barr virus-associated gastric carcinoma (EBVaGC) is a subset of gastric cancers linked to EBV infection. While the role of male hormones in cancers such as prostate, breast, and ovarian cancers is well-studied, their impact on EBVaGC remains less understood. This study aims to examine the effect of dihydrotestosterone (DHT) on EBVaGC, particularly focusing on its influence on the immune response. Methods: The study utilized the SNU719 EBVaGC cell line. Cells were treated with DHT to assess androgen receptor (AR) expression and the activation of signaling pathways, including NF-κB. The expression of MHC class I polypeptide-related sequence A (MICA) and its interaction with the NKG2D receptor on NK and T cells was evaluated. Cytotoxicity assays were conducted to determine DHT's effect on NK and T cell-mediated cytotoxicity, and proinflammatory cytokine gene expression was analyzed. Results: DHT significantly increased AR expression in EBVaGC cells and activated the NF-κB pathway, which led to increased transcription of target genes such as MICA and EBNA1. These changes enhanced the interaction with receptors on NK and T cells, thereby boosting their cytotoxicity against EBVaGC cells. Importantly, DHT did not upregulate proinflammatory cytokine genes. Conclusion: DHT enhances the immune response against EBVaGC by upregulating MICA and activating NK and T cells. These findings suggest potential therapeutic strategies targeting androgen signaling to improve anti-tumor immunity in EBVaGC. [ABSTRACT FROM AUTHOR]

Microneedle (MN) technology offers a powerful approach for transdermal delivery enabling painless injection and facilitating self‐administration without the need for professional assistance. However, the weak mechanical strength of MNs can lead to inefficient drug delivery and serious skin irritation if the MNs fracture during administration and leave fragments under the skin. Thus, the MNs need to be mechanically robust to avoid fracture during penetration through the skin while maintaining efficient drug delivery. Herein, the polymer‐based MNs with layer‐by‐layer (LbL) films of silica (SiO2) nanoparticles (NPs) and a polycation (poly(diallyldimethylammonium chloride) (PDADMAC)) followed by hydrothermal calcination are reinforced. The mechanical strength of the MNs is significantly improved after LbL assembly and shows lower threshold pressure to penetrate skins. Moreover, their drug loading and releasing properties are significantly enhanced due to an increase in the surface area and interfacial interaction. These SiO2 nanoparticle‐containing LbL thin films have great potential for the surface modification of 3D microstructured devices such as MNs, as evidenced by their enhanced mechanical strength and drug coating efficiency that result in a promising MN drug delivery model. [ABSTRACT FROM AUTHOR]

Artificial intelligence's (AI's) capacity for pattern recognition and automation in its decision making distinguishes this technology from conventional educational technology (U.S. Department of Education, 2023), and special education leaders need to provide guidance on how to critically evaluate the integration of AI tools into the instructional design process. We reviewed the definition of inclusion as presented in a national study conducted by The National Center on Educational Restructuring and Inclusion (1995) and isolated accessibility and equity as key values for supporting inclusion within instructional design. We explored the Universal Design for Learning instructional planning process document (UDL-IRN) for the presence of accessibility and equity as instructional values to develop guidance on instructional considerations reflective of ethics when adopting AI to the educational process. We synthesized the ethical foundations presented by the United States Department of Education's Office of Information Technology and the Universal Design for Learning instructional planning process (UDL-IRN) in conjunction with modified ethical assessments from the intelligent-technological, pedagogical, and content knowledge model developed by Celik (2023). We introduce an artificial intelligence ethical pedagogy aligned with inclusion values isolated from the instructional design document presented by Universal Design for Learning (2011). [ABSTRACT FROM AUTHOR]

The article explores the integration of three-dimensional (3D) printing, visual arts, social studies and drama with historical inquiry into silenced stories of school segregation as a potential pedagogical approach in art teacher education. Topics discussed include educational value of employing tableaux, significance of 3D printing for design thinking and artistic learning, use of theatre scriptwriting to understand histories, and visualization techniques to forge personal connections.

Background: Solid-organ transplant recipients (SOTRs) receiving immunosuppressive therapy are expected to have worse clinical outcomes from coronavirus disease 2019 (COVID-19). However, published studies have shown mixed results, depending on adjustment for important confounders such as age, variants, and vaccination status. Materials and Methods: We retrospectively collected the data on 7,327 patients hospitalized with COVID-19 from two tertiary hospitals with government-designated COVID-19 regional centers. We compared clinical outcomes between SOTRs and non-SOTRs by a propensity score-matched analysis (1:2) based on age, gender, and the date of COVID-19 diagnosis. We also performed a multivariate logistic regression analysis to adjust other important confounders such as vaccination status and the Charlson comorbidity index. Results: After matching, SOTRs (n=83) had a significantly higher risk of high-flow nasal cannula use, mechanical ventilation, acute kidney injury, and a composite of COVID-19 severity outcomes than non-SOTRs (n=160) (all P <0.05). The National Early Warning Score was significantly higher in SOTRs than in non-SOTRs from day 1 to 7 of hospitalization (P for interaction=0.008 by generalized estimating equation). In multivariate logistic regression analysis, SOTRs (odds ratio [OR], 2.14; 95% confidence interval [Cl],1.12-4.11) and male gender (OR, 2.62; 95% Cl, 1.26-5.45) were associated with worse outcomes, and receiving two to three doses of COVID-19 vaccine (OR, 0.43; 95% Cl, 0.24-0.79) was associated with better outcomes. Conclusion: Hospitalized SOTRs with COVID-19 had a worse prognosis than non-SOTRs. COVID-19 vaccination should be implemented appropriately to prevent severe COVID-19 progression in this population. [ABSTRACT FROM AUTHOR]

We challenge a common emphasis on documentation and assessment of learning for providing good education: from the mainstream of neoliberal accountability movement to the progressive Reggio Emilia schools. We develop these arguments through discussing: 1) immeasurableness of education and learning, 2) students' ownership/authorship of education and learning. We ground our conceptualization of educational assessment in critical dialogue, in a case of a student who requested assessment of her research project, and guided her peers and the teacher in providing different aspects of this assessment. We argue that documentation of learning on teacher's demand leads to surveillance, discipline, distraction, teacher-student distrust, and robbing of students from ownership of their education and thus it is anti-educational.

This study investigates the possibility of utilizing online learning data to design face-to-face activities in a flipped classroom. We focus on heterogeneous group formation for effective collaborative learning. Fifty-three undergraduate students (18 males, 35 females) participated in this study, and 8 students (3 males, 5 females) among them joined post-study interviews. For this study, a total of 6 student characteristics were used: three demographic characteristics obtained from a simple survey and three academic characteristics captured from online learning data. We define three demographic group heterogeneity variables and three academic group heterogeneity variables, where each variable is calculated using the corresponding student characteristic. In this way, each heterogeneity variables represents a degree of diversity within the group. Then, a two-stage hierarchical regression analysis was conducted to identify the significant group heterogeneity variables that influence face-to-face group achievement. The results show that the academic group heterogeneity variables, which were derived from the online learning data, accounted for a significant proportion of the variance in the group achievement when the demographic group heterogeneity variables were controlled. The interviews also reveal that the academic group heterogeneity indeed affected group interaction and learning outcome. These findings highlight that online learning data can be utilized to obtain relevant information for effective face-to-face activity design in a flipped classroom. Based on the results, we discuss the advantages of this data utilization approach and other implications for face-to-face activity design.

Purpose: Many teachers and students in the USA and various parts of the world are migrating some aspects of education online out of necessity. The purpose of this paper is to identify and describe strategies of the self-regulated learning (SRL) framework for K-12 students learning in online environments to support remote learning with online and digital tools during the COVID-19 pandemic. Design/methodology/approach: The SRL framework (Zimmerman, 2008) has been used consistently to support students in learning to work independently. This framework highlights three phases: planning, performing and evaluating. Previous research in K-12 online learning has yielded specific strategies that are useful. The paper identified and described the strategies to an audience seeking answers on how to meet the needs of students in online learning environment. Findings: The main types of strategies that have emerged from previous studies include asking students to consider how they learn online, providing pacing support, monitoring engagement and supporting families. Originality/value: Although the social crisis of COVID-19 is unique, prior research in online learning may be useful for supporting teacher practice and suggesting future research. Developing SRL skills of students will ensure the effectiveness of online learning that the field of education may ultimately focus on in the future.

How do children develop racial literacy? How do they make sense of and respond to the master narratives of race and racism? What role does elementary social studies education play in children's racial literacy development? I explored these questions as a parent-researcher, inquiring how my child, an Asian American elementary student, develops racial literacy as she learns U.S. history at school. In the following, I first situate my inquiry within the literature on social studies education from a critical race perspective. Next, I delineate my positionality as a critical race motherscholar and the rationale for studying my own child. Last, I present the findings from my inquiry and discuss its implications for elementary social studies education.

In this collaborative self-study, we examined our experiences of oppression and exclusion as tenure-track assistant professors possessing intersecting outsider statuses. We found that oppression is the elephant in the academy. We used self-study methodology, along with narrative inquiry, and textual and discursive analysis, to analyze our respective formal and informal student course evaluations, personal narratives and poems, and ongoing collective conversations. We found and analyzed not only the impact of these experiences on our physical, spiritual, emotional, and mental health, but also how they have impacted our work. Through our support system triad, we became vulnerable, critically aware, and mutually empathic -- all necessary components to building resilience to shame. We found some concerning commonalities problematizing the sanctity of the institution of the university: (a) students use course evaluations to punish professors because of unsafe content or critical pedagogical content and/or non-hegemonic identity markers; (b) similar mobbing tactics occur in private and public institutions in order to punish successful non-hegemonic/critical professors, although the behavior is more flagrant in private institutions, and (c) institutions provide lip service to diversity without creating internal mechanisms to sustain it. In essence, the institution carries on with status quo business as usual. We end with a discussion and conclusion about moving forward that allowed us to voice our discontents for a call to action against hegemony inside the academy and teacher education. We all have more work to do.

Decades of curriculum research have uncovered a persistent trend: white people are depicted as dominating the history of the United States, whereas communities of color and their experiences are omitted or misrepresented in social studies textbooks and curriculum standards. The message the resulting curriculum sends to children is that the United States is a country of white people, and people of color have little or no place in it. The author presents silenced-yet-powerful stories of three Americans--girls of Indigenous, Chinese, and Mexican ancestry--who fought for equal education in America in the last century. Their struggles all pre-dated that of the better-known African-American girl, Ruby Bridges, whose story is included in the first grade unit plan.

The daily encounters of explicit, implicit, direct, and indirect anti-Asian racism are the impetus of Sohyun An's work. Through critical race teaching and research, she seeks to debunk and disrupt curricular exclusions and misrepresentations of Asian Americans and their insidious effects on all children. This article is a part of such work. It offers a critical analysis of the systemic exclusion and misrepresentation of Asian Americans in the history curriculum. In the following paragraphs, she first briefly discusses why the curriculum, particularly history curriculum, matters by building on what Cridland-Hughes and King (2015) called a curriculum of violence. Next, she reviews previous studies and identify persistent trends in the curricular treatment of Asian Americans in the official story of the United States. She then explicates and troubles such curricular practices from the Asian critical race theory (AsianCrit) perspective (Chang, 1993; Iftikar & Museus, 2018). Last, she concludes with a call for a more inclusive presentation of Asian Americans in the official curriculum and highlight the many ways that Asian Americans are fighting for such a curriculum.

The passage of the 2015, Every Student Succeeds Act (ESSA), affords states funding for many new options to address the needs of learners. One of the prominent options is personalized learning (PL). This study sought to determine how states positioned PL in their state plans. This study used a qualitative research design to analyze state ESSA plans for presence of and relation to PL. From this analysis, four themes emerged, (a) definitions of PL, (b) goals of PL for students, (c) supports for PL, and (d) partnership for PL. The findings from this study suggested that many states contain aspects of PL in their state plans; however, there is little consensus of how to best implement PL. This article reported on these findings as well as offered guidance to policymakers and state departments of education on how to operationalize and implement PL.

In response to the COVID-19 pandemic, school closures across the country have altered the way educators teach and provide services to students. Engaging technologies in learning environments have become the primary mechanism delivering curriculum and maintaining the intellectual wellbeing of students. With the accelerated expansion of technologies across the K-12 curriculum, students' opportunities to engage with education-focused artificial intelligence (AI) software have increased (Touretzky et al., 2019). Students are beginning to interact with and orient themselves to AI through the use of home devices, such an Amazon Alexa (Jones, 2019). Many families and educators already have an Alexa device in their home that provides simple interactions with immediate feedback. Users can access Alexa's built-in functionalities, such as using search engines, providing weather information, or playing their favorite song (Wang, 2017). Any developer with knowledge of code can build the skills through the Alexa Voice Service platform (Amazon Alexa, n.d.). Amazon also provides users with premade blueprints for Alexa that are shells of skills made to be used by users of all technological abilities. The blueprints offer the average user guidance to create customized and personal voice user interface activities. In this article, the authors propose the use of AI devices, Amazon Alexa, and their prebuilt blueprints as an emerging form of educational technology. Educators can adapt the established blueprints to meet the needs of their students, mainly to help support distance-learning initiatives.

Abstract Background As the coronavirus disease 2019 (COVID-19) pandemic continues to progress, awareness about its long-term impacts has been growing. To date, studies on the long-term course of symptoms, factors associated with persistent symptoms, and quality of life after 12 months since recovery from acute COVID-19 have been limited. Methods A prospective online survey (First: September 8, 2020–September 10, 2020; Second: May 26, 2021–June 1, 2021) was conducted on recovered patients who were previously diagnosed with COVID-19 between February 13, 2020 and March 13, 2020 at Kyungpook National University Hospital. Responders aged between 17 and 70 years were included in the study. Overall, 900 and 241 responders were followed up at 6 and 12 months after recovery from COVID-19 in the first and second surveys, respectively. Clinical characteristics, self-reported persistent symptoms, and EuroQol-5-dimension (EQ5D) index score were investigated for evaluating quality of life. Results The median period from the date of the first symptom onset or COVID-19 diagnosis to the time of the survey was 454 (interquartile range [IQR] 451–458) days. The median age of the responders was 37 (IQR 26.0–51.0) years, and 164 (68.0%) responders were women. Altogether, 11 (4.6%) responders were asymptomatic, and 194 (80.5%), 30 (12.4%), and 6 (2.5%) responders had mild, moderate, and severe illness, respectively. Overall, 127 (52.7%) responders still experienced COVID-19-related persistent symptoms and 12 (5.0%) were receiving outpatient treatment for such symptoms. The main symptoms were difficulty in concentration, cognitive dysfunction, amnesia, depression, fatigue, and anxiety. Considering the EQ5D index scores, only 59.3% of the responders did not have anxiety or depression. Older age, female sex, and disease severity were identified as risk factors for persistent neuropsychiatric symptoms. Conclusion COVID-19-related persistent symptoms improved over time; however, neurological symptoms can last longer than other symptoms. Continuous careful observation of symptom improvement and multidisciplinary integrated research on recovered COVID-19 patients are required.

Objective: Insulin is a principal metabolic hormone. It regulates a plethora of metabolic pathways in peripheral tissues. The highly homologous insulin-like growth factor 1 (IGF-1), on the other hand, is important for development and growth. Recent studies have shown that insulin and IGF-1 signaling plays fundamental roles in the brain. Loss of insulin or IGF-1 receptors in astrocytes leads to altered glucose handling, mitochondrial metabolism, neurovascular coupling, and behavioral abnormalities in mice. Here, we aim to investigate molecular mechanisms by which insulin and IGF-1 signaling regulates astrocyte functions. Methods: IR-flox and IRKO primary astrocytes were treated with 100 nM insulin or IGF-1 for 6 h, and their transcriptomes were analyzed. Astrocytes with either IR deletion, IGF1R deletion or both were used to examine receptor-dependent transcriptional regulations using qPCR. Additional immunoblotting and confocal imaging studies were performed to functionally validate pathways involved in protein homeostasis. Results: Using next-generation RNA sequencing, we show that insulin significantly regulates the expression of over 1,200 genes involved in multiple functional processes in primary astrocytes. Insulin-like growth factor 1 (IGF-1) triggers a similar robust transcriptional regulation in astrocytes. Thus, over 50% of the differentially expressed genes are regulated by both ligands. As expected, these commonly regulated genes are highly enriched in pathways involved in lipid and cholesterol biosynthesis. Additionally, insulin and IGF-1 induce the expression of genes involved in ribosomal biogenesis, while suppressing the expression of genes involved in autophagy, indicating a common role of insulin and IGF-1 on protein homeostasis in astrocytes. Insulin-dependent suppression of autophagy genes, including p62, Ulk1/2, and several Atg genes, is blunted only when both IR and IGF1R are deleted. Conclusions: In summary, insulin and IGF-1 potently suppress autophagy in astrocytes through transcriptional regulation. Both IR and IGF1R can elicit ligand-dependent transcriptional suppression of autophagy. These results demonstrate an important role of astrocytic insulin/IGF-1 signaling on proteostasis. Impairment of this regulation in insulin resistance and diabetes may contribute to neurological complications related to diabetes.

The most widely used gradient-echo (GE) blood oxygenation level-dependent (BOLD) contrast has high sensitivity, but low specificity due to draining vein contributions, while spin-echo (SE) BOLD approach at ultra-high magnetic fields is highly specific to neural active sites but has lower sensitivity. To obtain high specificity and sensitivity, we propose to utilize a vessel-size-sensitive filter to the GE-BOLD signal, which suppresses macrovascular contributions and to combine selectively retained microvascular GE-BOLD signals with the SE-BOLD signals. To investigate our proposed idea, fMRI with 0.8 mm isotropic resolution was performed on the primary motor and sensory cortices in humans at 7 T by implementing spin- and gradient-echo (SAGE) echo planar imaging (EPI) acquisition. Microvascular-passed sigmoidal filters were designed based upon the vessel-size-sensitive ΔR2*/ΔR2 value for retaining GE-BOLD signals originating from venous vessels with ≤ 45 μm and ≤ 65 μm diameter. Unlike GE-BOLD fMRI, the laminar profile of SAGE-BOLD fMRI with the vessel-size-sensitive filter peaked at ∼ 1.0 mm from the surface of the primary motor and sensory cortices, demonstrating an improvement of laminar specificity over GE-BOLD fMRI. Also, the functional sensitivity of SAGE BOLD at middle layers (0.75–1.5 mm) was improved by ∼ 80% to ∼100% when compared with SE BOLD. In summary, we showed that combined GE- and SE-BOLD fMRI with the vessel-size-sensitive filter indeed yielded improved laminar specificity and sensitivity and is therefore an excellent tool for high spatial resolution ultra-high filed (UHF)-fMRI studies for resolving mesoscopic functional units.