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Derailed cytokine and immune cell networks account for the organ damage and the clinical severity of COVID-19 (refs. .sup.1-4). Here we show that SARS-CoV-2, like other viruses, evokes cellular senescence as a primary stress response in infected cells. Virus-induced senescence (VIS) is indistinguishable from other forms of cellular senescence and is accompanied by a senescence-associated secretory phenotype (SASP), which comprises pro-inflammatory cytokines, extracellular-matrix-active factors and pro-coagulatory mediators.sup.5-7. Patients with COVID-19 displayed markers of senescence in their airway mucosa in situ and increased serum levels of SASP factors. In vitro assays demonstrated macrophage activation with SASP-reminiscent secretion, complement lysis and SASP-amplifying secondary senescence of endothelial cells, which mirrored hallmark features of COVID-19 such as macrophage and neutrophil infiltration, endothelial damage and widespread thrombosis in affected lung tissue.sup.1,8,9. Moreover, supernatant from VIS cells, including SARS-CoV-2-induced senescence, induced neutrophil extracellular trap formation and activation of platelets and the clotting cascade. Senolytics such as navitoclax and a combination of dasatinib plus quercetin selectively eliminated VIS cells, mitigated COVID-19-reminiscent lung disease and reduced inflammation in SARS-CoV-2-infected hamsters and mice. Our findings mark VIS as a pathogenic trigger of COVID-19-related cytokine escalation and organ damage, and suggest that senolytic targeting of virus-infected cells is a treatment option against SARS-CoV-2 and perhaps other viral infections. Virus-induced senescence is a central pathogenic feature in COVID-19, and senolytics, which promote apoptosis of senescent cells, can reduce disease severity in hamsters,mice, as well as humans infected with SARS-CoV-2., Author(s): Soyoung Lee [sup.1] [sup.2] [sup.3] , Yong Yu [sup.4] , Jakob Trimpert [sup.5] , Fahad Benthani [sup.4] , Mario Mairhofer [sup.4] , Paulina Richter-Pechanska [sup.1] , Emanuel Wyler [sup.2] [...]

This paper explores ways in which Roland Barthes' discussion of the encyclopaedia provides us with resources for thinking about education and research practice today. What Barthes addresses in his essay 'The Plates of the Encyclopedia' is a particular encyclopaedia, the "Encyclopédie" produced by Denis Diderot and Jean le Rond d'Alembert, which was published in France between 1751 and 1772. This is commonly referred as the first of a form that we recognise as the encyclopaedia today. I begin with Barthes' analysis and critique of the "Encyclopédie." Barthes, writing in 1964, engages with the "Encyclopédie" as an iconic product of its time, seeing it as conditioned by and, in effect, reinforcing a particular way of experiencing the world. Next, I consider ways in which a parallel critique is pertinent today. I explore some current examples of encyclopaedic form in relation to education and educational research. The purpose of this is to examine the interplay between particular cultural products and their society, in which not only certain types of knowledge but also a certain conception of knowledge are produced and reinforced. So, it will not be the purpose of this paper to provide direct analysis or critique of the Enlightenment, or to provide a historical account of knowledge. Rather, what I am interested in is problematising a particular understanding of language and knowledge that arises through these cultural products, particularly with regard to educational inquiry. This lays the way for thoughts expressed by Gilles Deleuze and Félix Guattari in "What is Philosophy?" which, as I shall try to show, are of help in furthering the analysis of the dominant research culture's use of such products and in imagining the task of education and research differently.

Literature in the field of minority parent participation has focused on cultural differences and cultural mismatch as reasons for the difficulties that minority parents face in schools and has relied on a framework of cultural sensitivity in exploring the issues. Soyoung Lee proposes that the real issue underlying the dynamics between minority parents and schools and the reasons their voices are silenced are undeniably about race, power, and the exercise of racial privilege. She uses a personal narrative to illuminate how racism and power lead to the silencing of minority parents, and she makes recommendations for researchers, schools, and teacher educators to acknowledge and act on such forms of injustice.

This paper explores the concept of "Gelassenheit" as developed in the later thought of Martin Heidegger. It seeks to show the relevance of this to aspects of education, especially to the ways that teaching can be enhanced in order to do better justice both to the learners and to what is studied. Thinking in this way helps to overcome the dominance of representational thought, a kind of thinking that imposes barriers on the understanding and restrictions on how the world can come to be. In the end the thinking illustrated by "Gelassenheit" constitutes a more responsible and more responsive relationship to the truth. My paper provides examples of ways that this can enhance education. In the end, with a caveat, I revisit and re-examine aspects of Heidegger's work about which I think there is reason to be cautious. This is to encourage a degree of vigilance in relation to Heidegger's thought, but in a way that does not deny its powerful insights.

The importance of Levinas's philosophy for education has been widely discussed. In 'Levinas: Ethics or Mystification?' however, Alistair Miller questions whether Levinas's work is of value at all, raising doubts about whether his philosophy can, in any way, be helpful when it comes to practical ethical decision-making, especially within education. Levinas's ethics, he argues, in the light of its lack of rational argument, amounts only to poetic imagery and mystical incantation. The purpose of this paper is to read Levinas in relation to education against this indictment by Miller. This paper proceeds by investigating the basis of Miller's arguments, in the light of exegesis of relevant aspects of Levinas's work. My purpose is not the positing of a new system or the formulation of systematic ideas of ethics but rather achieving an understanding of human experience, especially in contexts of teaching and learning, under a different, more accurate description. In doing so I attempt to show that Levinas's philosophy indeed provides a ground for ethics--that is, a means of understanding the practicality of ethics differently, beyond systematic approaches. In the last section, where education is discussed more directly, ethics will be seen as its very condition.

The development of place attachment is an important learning objective in geography education because it plays a significant role in people's behaviors toward protecting and acting on behalf of places. This study demonstrates the effects of selecting and presenting favorite places (SPFP) strategy in enhancing students' place attachment. The SPFP activity was expected to establish the participants' positive stance toward their chosen places and promote the consistent maintenance of their initial attitude. It builds on the preference for consistency, or the desire and tendency to behave predictably by acting similarly across diverse situations. We asked the participants to select their favorite places in a city, to visualize them using Google Earth, and to present their activities. As a result, the participants increased their place attachment, which is composed of place identity and place dependence.

INTRODUCTION: Despite prior research on the association between sarcopenia and cognitive impairment in the elderly, a comprehensive model that integrates various brain pathologies is still lacking. METHODS: We used data from 528 non‐demented older adults with or without sarcopenia in the Catholic Aging Brain Imaging (CABI) database, containing magnetic resonance imaging scans, positron emission tomography scans, and clinical data. We also measured three key components of sarcopenia: skeletal muscle index (SMI), hand grip strength (HGS), and the five times sit‐to‐stand test (5STS). RESULTS: All components of sarcopenia were significantly correlated with global cognitive function, but cortical thickness and amyloid‐beta (Aβ) retention had distinctive relationships with each measure. In the path model, brain atrophy resulting in cognitive impairment was mediated by Aβ retention for SMI and periventricular white matter hyperintensity for HGS, but directly affected by the 5STS. DISCUSSION: Treatments targeting each sub‐domain of sarcopenia should be considered to prevent cognitive decline. Highlights: We identified distinct impacts of three sarcopenia measures on brain structure and Aβ.Muscle mass is mainly associated with Aβ and has an influence on the brain atrophy.Muscle strength linked with periventricular WMH and brain atrophy.Muscle function associated with cortical thinning in specific brain regions.Interventions on sarcopenia may be important to ease cognitive decline in the elderly. [ABSTRACT FROM AUTHOR]

Background: Recent interest has surged in the locus coeruleus (LC) for its early involvement in Alzheimer's disease (AD), notably concerning the apolipoprotein ɛ4 allele (APOE4). Objective: This study aimed to discern LC functional connectivity (FC) variations in preclinical AD subjects, dissecting the roles of APOE4 carrier status and amyloid-β (Aβ) deposition. Methods: A cohort of 112 cognitively intact individuals, all Aβ-positive, split into 70 APOE4 noncarriers and 42 carriers, underwent functional MRI scans, neuropsychological assessments, and APOE genotyping. The research utilized seed to voxel analysis for illustrating LC rsFC discrepancies between APOE4 statuses and employed a general linear model to examine the interactive influence of APOE4 carrier status and Aβ deposition on LC FC values. Results: The investigation revealed no significant differences in sex, age, or SUVR between APOE4 carriers and noncarriers. It found diminished LC FC with the occipital cortex in APOE4 carriers and identified a significant interaction between APOE4 carrier status and temporal lobe SUVR in LC FC with the occipital cortex. This interaction suggested a proportional increase in LC FC for APOE4 carriers. Additional notable interactions were observed affecting LC FC with various brain regions, indicating a proportional decrease in LC FC for APOE4 carriers. Conclusions: These findings confirm that APOE4 carrier status significantly influences LC FC in preclinical AD, showcasing an intricate relationship with regional Aβ deposition. This underscores the critical role of genetic and pathological factors in early AD pathophysiology, offering insights into potential biomarkers for early detection and intervention strategies. [ABSTRACT FROM AUTHOR]

Allergic asthma is a type 2 immune-response-mediated chronic respiratory disease. Mast cell activation influences the pathogenesis and exacerbation of allergic asthma. Therefore, the development of mast cell-targeting pharmacotherapy is important for managing allergic airway inflammation. We investigated the efficacy of hispidulin (HPD), natural flavone, in a mast-cell-mediated ovalbumin (OVA)-induced allergic airway inflammation model. HPD alleviated symptoms of allergic asthma and decreased the levels of immunoglobulin (Ig) E, type 2 inflammation, immune cell infiltration, and mast cell activation in the lung. Furthermore, in vivo analysis confirmed the efficacy of HPD through the evaluation of IgE-mediated allergic responses in a mast cell line. HPD treatment inhibited mast cell degranulation through inhibition of the FcεR1 signaling pathway and suppressed the expression of inflammatory cytokines (TNF-α, IL-4, IL-6, and IL-13) through suppression of the NF-κB signaling pathway. The antioxidant effects of HPD in activated mast cells were identified through modulation of antioxidant enzymes and the Nrf2/HO-1 signaling pathway. In conclusion, HPD may be a potential therapeutic candidate for allergic airway inflammation of asthma and acts by suppressing mast cell activation and oxidative stress. [ABSTRACT FROM AUTHOR]

Hooking up is a popular trend on college campuses (Victor, 2012). Traditionally, hooking up has been viewed as a sexual risk behavior and research has focused on implications such as the spread of sexually transmitted infections (STI) or unintended pregnancy (Downing-Matibag & Geisinger, 2009). However, hookup behavior may also influence attitudes toward future romantic relationships and young adult perceptions of their ability to be in romantic relationships (Riggio, Weiser, Valenzuela, Lui, Montes & Heuer, 2009; Sassler, 2010). In addition, gender plays a critical role in heterosexual hookup behavior, since there is often a power differential present (Cook-Lindsay, 2013; Lovejoy, 2015), and must be closely examined. Thus, this literature review seeks to examine heterosexual hookup behavior and future romantic relationships. We suggest that hookups are linked to future romantic relationships through romantic relationship self-efficacy, or one's perception of their ability to be in a romantic relationship (Riggio et al., 2013). In addition, upon our review, there are clear gender differences in perceptions of heterosexual hookups which may contribute to perceptions of future romantic relationships. This is discussed in depth and suggestions for future research are provided.

Evidence-based writing is a complex standard in the Common Core State Standards that has taken center stage in the writing curriculum. Students must demonstrate proficiency in making claims based on evidence and explain how the evidence supports their claim. This is a challenging task for all students, but for English learners, it can be especially overwhelming. The author describes a series of lessons that teachers can use to introduce evidence-based writing in three steps to English learners. The author developed the three-step lessons for use with English learners after observing teachers and students struggling with evidence-based writing in linguistically diverse settings. The lessons incorporate literature on best practices in writing development for second-language learners, and the descriptions of the lessons are supported with examples from a sixth-grade English as a Second Language classroom.

Cisplatin is a widely used anti-cancer drug for treating solid tumors, but it is associated with severe side effects, including nephrotoxicity. Various studies have suggested that the nephrotoxicity of cisplatin could be overcome; nonetheless, an effective adjuvant drug has not yet been established. Oleanolic acid acetate (OAA), a triterpenoid isolated from Vigna angularis, is commonly used to treat inflammatory and allergic diseases. This study aimed to investigate the protective effects of OAA against cisplatin-induced apoptosis and necroptosis using TCMK-1 cells and a mouse model. In cisplatin-treated TCMK-1 cells, OAA treatment significantly reduced Bax and cleaved-caspase3 expression, whereas it increased Bcl-2 expression. Moreover, in a cisplatin-induced kidney injury mouse model, OAA treatment alleviated weight loss in the body and major organs and also relieved cisplatin-induced nephrotoxicity symptoms. RNA sequencing analysis of kidney tissues identified lipocalin-2 as the most upregulated gene by cisplatin. Additionally, necroptosis-related genes such as receptor-interacting protein kinase (RIPK) and mixed lineage kinase domain-like (MLKL) were identified. In an in vitro study, the phosphorylation of RIPKs and MLKL was reduced by OAA pretreatment in both cisplatin-treated cells and cells boosted via co-treatment with z-VAD-FMK. In conclusion, OAA could protect the kidney from cisplatin-induced nephrotoxicity and may serve as an anti-cancer adjuvant. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD), a chronic disorder affecting the colon and rectum, involves the overproduction of pro-inflammatory cytokines causing damage to tight junctions (TJ) in the intestinal epithelial cells and chronic inflammation. The current mainstay of treatment, sulfasalazine, often causes adverse effects, thereby necessitating the exploration of alternative herbal medicines with fewer side effects. Portulaca oleracea L. (P. oleracea), a traditional medicinal herb, contains feruloyl amide compounds. We synthesized new compounds by conjugating ferulic acid (FA) with (±)-octopamine. Our study focused on novel FA derivatives that demonstrate protective effects against the intestinal epithelial barrier and inflammatory responses. In lipopolysaccharide-induced cells, C1 and C1a inhibited the production of inflammatory mediators. In Caco-2 cells, these compounds maintained the TJ protein expression, thereby demonstrating their protective effects on the epithelial barrier. In a mouse model of dextran sulfate sodium-induced IBD, a treatment with these compounds ameliorated features including a body weight reduction, colon shortening, an increased disease activity index, and histopathological changes. Furthermore, C1a demonstrated greater efficacy than C1 at the same concentration. These findings suggest that the novel FA derivative (C1a) effectively alleviates clinical signs and inflammatory mediators in IBD, making these compounds potential candidates as natural medicines for the treatment of IBD. [ABSTRACT FROM AUTHOR]

Objective: Despite the suggested topiramate serum level of 5–20 mg/L, numerous institutions have observed substantial drug response at lower levels. We aim to investigate the correlation between topiramate serum levels, drug responsiveness, and adverse events to establish a more accurate and tailored therapeutic range. Methods: We retrospectively analyzed clinical data collected between January 2017 and January 2022 at Seoul National University Hospital. Drug responses to topiramate were categorized as "insufficient" or "sufficient" by reduction in seizure frequency ≥ 50%. A population pharmacokinetic model estimated serum levels from spot measurements. ROC curve analysis determined the optimal cutoff values. Results: A total of 389 epilepsy patients were reviewed having a mean dose of 178.4 ± 117.9 mg/day and the serum level, 3.9 ± 2.8 mg/L. Only 5.6% samples exhibited insufficient response, with a mean serum level of 3.6 ± 2.5 mg/L while 94.4% demonstrated sufficient response, with a mean 4.0 ± 2.8 mg/L, having no statistical significance. Among the 69 reported adverse events, logistic regression analysis identified a significant association between ataxia and serum concentration (p = 0.04), with an optimal cutoff value of 6.5 mg/L. Interpretation: This study proposed an optimal therapeutic concentration for topiramate based on patients' responsiveness to the drug and the incidence of adverse effects. We recommended serum levels below 6.5 mg/L to mitigate the risk of ataxia‐related side effects while dose elevation was found unnecessary for suboptimal responders, as the drug's effectiveness plateaus at minimal doses. [ABSTRACT FROM AUTHOR]

Velufenacin (DA‐8010) is a new muscarinic receptor antagonist under development for the treatment of overactive bladder. This study aimed to evaluate the effect of food on the pharmacokinetics (PK) and safety of velufenacin in healthy subjects. A randomized, open‐label, single‐dose, 4‐sequence, 4‐treatment, 4‐period crossover study was conducted. Subjects received a single oral dose of velufenacin 2.5 or 5 mg in a fasted or fed (high‐fat meal) state in each period with a 7‐day washout. PK parameters including maximum plasma concentration (Cmax) and area under the concentration‐time curve from time 0 to the last measurable point were compared between the fed and fasted states. Twenty‐seven subjects completed the study. The mean area under the concentration‐time curve from time 0 to the last measurable point of the velufenacin 2.5 and 5 mg doses under the fed condition showed a 1.5‐ and 1.3‐fold increase, respectively, compared to the fasted condition. The corresponding values for Cmax were a 2.3‐ and 2.0‐fold increase, respectively. The time to reach Cmax was comparable regardless of the dose or food intake, showing median values of 4.5‐5.0 hours. These results suggest a modest increase of velufenacin absorption by food intake. Velufenacin was generally safe and well tolerated at the 2.5 and 5 mg doses regardless of food. [ABSTRACT FROM AUTHOR]

In exploring why American mothers spend more time on care work compared to prior decades while increasingly engaging in paid work, Hays (1997) attributed women's actions to intensive motherhood (IM) ideology. Hays also asserted that women purposedly adhere to IM to resist an increasingly neoliberal market-based society by dedicating time and effort to nurturing children and family life. Here, we undertake a content analysis to take stock of IM literature's evolution in recent decades. Specifically, we examine scholars' treatment of how women adhere to IM, and why and whether women do so in resistance to neoliberalism. We found that while scholars consistently cite and echo Hays (1997) on how women adhere to IM, most depart from Hays (1997) by positing women adhere to live up to an ideal of being a perfect mother due to the pervasive nature of IM. We also found many scholars focus on the possibility of resisting IM ideology itself rather than Hays's (1997) perspective that women employ the ideology to resist neoliberalism. These findings raise questions about how women's agency manifests in the IM context, and concerns about embedded assumptions that limit our understanding of women's realities. Implications are discussed. [ABSTRACT FROM AUTHOR]