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In this randomized control study, we evaluated science teachers' pedagogical practices via classroom observations following ongoing, intensive, and structured instructional support sessions. These sessions included virtual professional development (VPD) and virtual mentoring and coaching (VMC) that accompanied a literacy-infused science curriculum. Using a low-inference observational instrument, we explored the direct impact of VPD and VMC on fifth-grade science teachers' observed time allocation in a randomized controlled trial (RCT) validation study. The observations were collected three times during science instruction from 121 teachers in 68 schools from 35 public school districts in the U.S. state of Texas, during the 2017-2018 school year. Preliminary findings revealed pedagogical differences in time allocation among teachers between treatment and control classrooms. We identified improved instructional practices within treatment classrooms, which suggests the intervention had a positive effect by enhancing the quality of pedagogy as well as the content-area instruction in science.

Collaborative problem-solving (CPS) involves the interaction and interdependence of students' social and cognitive skills, making it a complex learning process. To delve into the complex dynamics of CPS, previous research has categorized socio-cognitive roles, providing insights into social-cognitive frameworks. However, despite the specific cognitive and social interaction structures employed by roles to engage in CPS interactions, most existing research primarily focuses on individual roles, neglecting inter-role interactions. To fill this gap, twelve triad groups were formed by engaging 36 undergraduate students in online CPS activities to examine differences in social and cognitive interaction structures across different roles and group compositions. Additionally, analyze the differences in CPS processes among various group compositions. The analyses identified five roles ("Lurkers," "Followers," "Drivers," "Influential Actors," and "Innovators") and three group compositions ("Balanced groups," "Decentralized groups," and "Power Struggle groups"). The socio-cognitive structure of Balanced groups, along with other evidence, indicates effective information sharing and negotiation interactions. In contrast, "Decentralized" and "Power Struggle groups" exhibited various deficiencies in their socio-cognitive structures, negatively impacting group collaboration processes. These insights provide educators with a comprehensive guide to fostering effective group compositions and role dynamics in online CPS settings, thereby enhancing the overall success of CPS. Additionally, possible activity design considerations and scaffolding strategies are also discussed.

Faithful genome partition during cell division relies on proper congression of chromosomes to the spindle equator before sister chromatid segregation. Here we uncover a kinesin-7 motor, kinetochore-associated kinesin 1 (KAK1), that is required for mitotic chromosome congression in Arabidopsis. KAK1 associates dynamically with kinetochores throughout mitosis. Loss of KAK1 results in severe defects in chromosome congression at metaphase, yet segregation errors at anaphase are rarely observed. KAK1 specifically interacts with the spindle assembly checkpoint protein BUB3.3 and both proteins show interdependent kinetochore localization. Chromosome misalignment in BUB3.3-depleted plants can be rescued by artificial tethering of KAK1 to kinetochores but not vice versa, demonstrating that KAK1 acts downstream of BUB3.3 to orchestrate microtubule-based chromosome transport at kinetochores. Moreover, we show that KAK1's motor activity is essential for driving chromosome congression to the metaphase plate. Thus, our findings reveal that plants have repurposed BUB3.3 to interface with a specialized kinesin adapted to integrate proper chromosome congression and checkpoint control through a distinct kinetochore design.

Coordinate geometry is an important part of mathematics. It helps students develop thinking, logic, and problem-solving skills. This study was conducted to test the effectiveness of the CORE learning model in promoting students' mathematical problem-solving skills when they learn the method of coordinates in a plane. Consequently, this study used mixed methods as a quasi-experiment with a non-equivalent control group design, with assessment tools including pretest, post-test, classroom observation, and attitude survey. The data collected were quantitatively analyzed with JASP and qualitatively analyzed. The analysis findings demonstrate that the students in the experimental group performed better academically in terms of knowledge and problemsolving skills and had more optimistic learning attitudes. In particular, a correlation test was performed on the pre-and post-test scores of the experimental group. It showed that with a correlation level of 0.810, according to the Hopkins reference table, the scores of the students in the experimental group were higher than those of the control group due to the effectiveness of the CORE learning model in promoting students' problem-solving abilities. In addition, the study identified certain limitations and proposed new research directions for the future.

Modern society is complex and ever-changing. To adapt to this situation, the level of education must be continuously enhanced, and college students who are about to enter society are the group that needs the most attention. As a creative and effective teaching organizational form and teaching strategy, the cooperative learning method plays an important role in education and teaching. This article research aims to achieve the following two goals: (1) Compare students' learning abilities after the cooperative learning method and traditional teaching method. (2) Compare students' core competencies after the cooperative learning method and traditional teaching method. The participants in this study were students studying physics at Guangxi Normal University for Nationalities in China. It includes a control group consisting of 30 students and an experimental group consisting of 30 students. The research tool used a Likert scale question, and the data were analyzed using normal distribution and standard deviation. The research results show that students' learning ability and core competencies after the cooperative learning method are better than traditional teaching method (P<0.01).

Purpose: This study investigates the role of the engineering education environment created by the implementation of the "Plan for Educating and Training Outstanding Engineers" (PETOE) on the professional capability development of engineering students from the perspective of students' experience. Design/Approach/Methods: This study uses data from the National Engineering Student Survey and multiple regression analysis to explore the role of institutional resources and support, teaching reforms, and interpersonal interaction on the professional development of engineering students. Findings: The opportunities for on-campus practical activities provided by the institution, content of the teachers' teaching, teaching methods, comprehensive coursework assessment, and interpersonal interactions contributed to the development of students' engineering competencies, with limited contributions from research-based teaching methods. Internship opportunities and international exchange environments were negatively associated with the development of engineering skills in an "unexpected" manner. Originality/Value: Focusing on students' experiences of engineering education reform, this study comprehensively evaluates the implementation of there form measures adopted under PETOE. Furthermore, it assesses how corresponding changes in the general educational environment relate to students' professional capability development. Thus, this study addresses an important research gap in educational reform--the lack of domestic empirical studies in China.

A central objective of science education is to foster a profound comprehension of fundamental scientific principles among students. Research has shown that a highly integrated knowledge structure is a key factor in achieving a deep understanding. This research has developed a friction force conceptual framework to model students' different understandings of friction force from a knowledge integration perspective. Utilizing the established conceptual framework, this study devised and implemented an evaluation of friction force among a cohort of 598 grade-10 students in China. The assessment outcomes were then analyzed quantitatively and qualitatively. The results show that the conceptual framework model effectively represents the knowledge structures of students at different levels of knowledge integration, and the students' understanding of friction force can be divided into three levels: novice, intermediate, and expert. Furthermore, emphasizing the passivity of friction force can help students gain a deeper understanding of the concept of friction force, thereby forming a more comprehensive knowledge structure. This study provides an effective strategy for students to progress from novices to experts.

The Dong Grand Songs, renowned for their polyphonic choral arrangements, are a vital cultural heritage of the Dong ethnic group. This study investigates the contemporary educational approaches to the literacy and development of the Dong Grand Songs in Guangxi, China. Employing a qualitative design, the research includes fieldwork, in-depth interviews, participant observation, and document analysis. Key informants comprise school administrators, teachers, song teachers, cultural inheritors, students, and community members. The findings reveal that integrating Dong Grand Song courses into primary and secondary school curricula, with support from song teachers and cultural inheritors, effectively enhances musical literacy and preserves this tradition. However, challenges such as youth migration, modern entertainment influences, and the aging population of song masters threaten the continuity of this cultural heritage. The study suggests comprehensive approaches, including economic support for rural areas, increased public awareness, and sustainable cultural programs, are necessary to address these challenges. This research provides valuable insights for policymakers, educators, and cultural practitioners on preserving intangible cultural heritage and promoting musical literacy through education.

This research aimed to (1) study the current situation and existing problems of undergraduate students 'understanding of intangible cultural heritage, (2) develop a curriculum of intangible cultural heritage based on experiential learning theory, and (3) compare undergraduate students' understanding of intangible cultural heritage before and after teaching. The sample group was 50 students who were selected to attend the Intangible Cultural Heritage curriculum in the spring semester of 2023. The research tools were (1) Lesson plans (2) a Questionnaire on the current situation and existing problems of undergraduate students 'understanding of intangible cultural heritage, (3) an Interview form on the current situation and existing problems regarding students' understanding of intangible cultural heritage, (4) understanding intangible cultural heritage test, (5) Observation of Students' Behavior form, and (6) Interview form on opinions about teaching. This study was conducted in three steps: (1.) The study on the current situation and existing problems of undergraduate students 'understanding of intangible cultural heritage, (2.) The development of a curriculum of intangible cultural heritage based on experiential learning theory, and (3.) The experimental and improvement of curriculum. The results of the study showed that: 1) The current situation and existing problems of the intangible cultural heritage of college students have three aspects: students, teachers, and the school environment. The most important current situation and existing problems of undergraduate students 'understanding of intangible cultural heritage was the school environment aspects. 2) The Curriculum of intangible cultural heritage based on experiential learning theory includes 6 elements: Principle, Goal Contents, Learning process, Learning resource, and Evaluation. The learning process consisted of 4 steps: (1) Concrete Experience, (2) Reflective Observation, (3) Abstract Conceptualization, (4) Active Experimentation 3) The curriculum based on experiential learning theory can improve undergraduate students' understanding of intangible cultural heritage.

Practitioner-focused educational doctoral programs have grown substantially in recent years. Dissertations in Practice (DiPs), which are the culminating research report and evaluation method in these programs, differ from traditional PhD dissertations in their focus on addressing a problem of practice and on connecting theories with practice. As part of our ongoing program evaluation, we reviewed DiPs from doctoral students who graduated from an online asynchronous Educational Doctoral program in Learning Design and Technologies at the University of South Carolina. Findings revealed that most students chose a pragmatic philosophical paradigm, adopted a mixed methods research design, reported an action research intervention implemented with populations in K-12 schools, used surveys and interviews as data sources, and analyzed data with descriptive/inferential statistics and thematic analysis. Implications for the program curriculum are discussed.

Redox reaction is a core chemical concept. However, its abstract nature makes it very difficult for students. Students' conceptual structure reflects their mastery of concepts, which helps teachers implement targeted educational strategies. This study aimed to explore the conceptual structures of redox reaction held by students (grades 10 to 12) by employing MDS and HCA. A total of 606 students participated, with 195 students in 10th grade, 202 in 11th grade, and 209 in 12th grade. The results indicated that three-dimensional solutions were appropriate for the conceptual structures of 10th and 12th graders, while 11th graders demonstrated two-dimensional solutions. All students grouped the 15 concepts related to redox reaction into two large clusters: metrology and the redox reaction process. Moreover, both 10th and 12th graders further subdivided the 15 concepts into four subclusters: metrology, oxidation process, reduction process, and chemical reaction. Students' conceptual structures were rational across all three grades. The conceptual structures of 10th and 12th graders were more refined than those of 11th graders, and there was no significant difference between the conceptual structures of 10th and 12th graders. 11th graders learned about electrochemistry and tended to confuse concepts related to redox reaction with those related to electrochemistry.

For more than a decade, the Financial Technology (FinTech) industry has been growing, and it has reshaped how payments were made and brought new financial service products to the market. FinTech has created innovative disruptions to traditional, long-established financial institutions (e.g., banks and investment firms) in financial services markets. The worldwide blooming of FinTech has caused universities around the globe to teach their students (particularly those in the IT and finance disciplines) about practical and contemporary knowledge on FinTech. This paper discusses our recent survey study to investigate the status quo of offering FinTech education and training by Australian universities. Our study involved two rounds of online data collection (one in November 2021 and the other one in June 2022) from 41 sample universities in Australia. Among our various findings, we observed that, although Australian universities are increasingly aware of the importance of and the demand for FinTech studies, FinTech has still not yet become a mainstream study discipline. This observation indicates that, in Australia, FinTech studies have generally gone through the inception stage and entered the growth stage.

Numerous scholars have investigated the determinants of university innovation efficiency. However, the internal governance aspects of universities and their interactions with the external environment are frequently neglected. Therefore, this study, grounded in the framework of embeddedness theory, employed the Stochastic Frontier Analysis method to empirically analyze innovation efficiency in Chinese universities. The results indicated that competitive threats significantly improved university innovation efficiency, whereas bureaucracy and international openness exhibited adverse effects, which were alleviated in regions with greater marketization.

Objectives: Previous studies have widely demonstrated that inhibition of return (IOR) with audiovisual targets decreases due to audiovisual integration (AVI). It is currently unclear, however, whether the impaired AVI in children with ADHD has effects on IOR. The present study used the cue-target paradigm to explore differences between the IOR of audiovisual targets and the IOR of visual targets in ADHD and typically developing (TD) children. Method: A total of 81 native Chinese speakers aged 6 to 13 years were recruited, including 38 children with ADHD and 43 age- and sex-matched TD children. Results: The results showed that there was a smaller magnitude of IOR with audiovisual targets as compared with visual targets in the two groups. Importantly, the reduction of IOR in audiovisual conditions was significantly smaller in children with ADHD than in children with TD. Race model analyses further confirmed that differences in IOR between ADHD and TD are due to deficits of audiovisual integration in ADHD. Conclusion: The results indicated that children with ADHD have impaired audiovisual integration, which has a minimal impact on IOR.

There is no relationship more vital than the one a child shares with their primary caregivers early in development. Yet many children worldwide are raised in settings that lack the warmth, connection, and stimulation provided by a responsive primary caregiver. In this study, we used data from the Bucharest Early Intervention Project (BEIP), a longitudinal study of institutionally-reared and family-reared children, to test how caregiving quality during infancy is associated with average EEG power over the first 3.5 years of life in alpha, beta, and theta frequency bands, and associations with later executive function (EF) at age 8 years. The sample comprised 189 children (129 institutionally-reared; 60 family-reared) who contributed data on observed caregiving quality during infancy (baseline; average age of 22 months), resting EEG power at baseline, 30, and 42 months, and performance-based data on a series of EF tasks at 8 years. Using Bayesian estimation, observed caregiving quality at baseline was marginally linked with higher average alpha and beta power, and lower theta power, from baseline to 42 months. In turn, higher average beta power and lower average theta power were marginally associated with higher EF at 8 years. In indirect effects models, higher caregiving quality at baseline was associated with higher EF at 8 years, with a marginal indirect effect through average theta power from baseline to 42 months. Variation in the quality of the early caregiving environment may be associated with later executive function, which is partially underpinned by individual differences in brain activity during early childhood.

Research in STEM education has focussed on integrated STEM projects that combine knowledge and skills across science, technology, engineering, and mathematics. These integrated STEM projects are typically designed by teachers or researchers addressing a limited range of topics that do not always cater well to the diversity of interest among children and adolescents. By contrast, self-selected projects where students have more choices and autonomy in selecting their own projects are relatively rare. Consequently, there is a gap in the literature on students' learning experiences when they choose and develop their own STEM projects. This study aims to examine the classroom experience and enactment of a high school STEM course designed for Grade 9 and 10 students (14 to 16 years old) to carry out a project of their choice aligned with the theme of sustainability. A case study methodology was used to investigate eight students' lived experiences in making connections to STEM. The study reveals the nature of students' self-directed learning experiences as they chose their own topics of exploration and subsequently developed their respective STEM-related projects. It also illuminates the alignments and tensions between STEM integration and various aspects of students' self-directed learning, including intrinsic motivation, open-ended tasks, goal setting, design thinking, collaboration with external partners, curriculum constraint, and time management. The implications of the study encompass student autonomy and agency, the significance of authentic problems and themes in STEM education, and the role of curriculum in facilitating self-selected projects.

While the effect of reading strategies on L2 test performance has been extensively researched, the effect of test-taking strategies remains underexplored, with mixed results due to varying contextual factors. This study, therefore, investigated the latent structure of test-taking strategies and the relationships among test-taking strategies, lexico-grammatical ability, and test performance in a test of local-level reading comprehension questions (LRCQs) by 217 Chinese EFL learners. Confirmatory factor analyses revealed test-taking strategies could be composed of test-management and test-wiseness strategies. Structural equation modeling provided further empirical evidence for this conceptual distinction, as only test-management strategies were significantly affected by lexico-grammatical ability. However, while lexico-grammatical ability had a large effect on test performance, neither test-management nor test-wiseness strategies had a significant impact on test performance. This study helps researchers and teachers better understand the test-taking strategies at play in LRCQs and their impact on test performance and carries implications for L2 reading pedagogy.

Augmentative and alternative communication (AAC) refers to methods and tools that facilitate communication for individuals with limited functional speech. This study aims to present and analyse the research status of AAC interventions for children with special needs in mainland China using a bibliometric analysis approach. The researcher conducted a literature search in the China National Knowledge Infrastructure (CNKI) database to identify relevant studies. Based on the literature search, 80 articles met the inclusion criteria. The research literature spans from 2007 to 2022, with a notable increase in publications after 2015. The majority of studies focus on children with autism, while other disabilities, such as intellectual disabilities and cerebral palsy, receive less attention. AAC interventions primarily utilize low-technology communication aids, with limited use of high-technology tools. Research on AAC interventions for children with special needs in mainland China has grown recently. However, it still falls short of meeting the potential demand to promote the application and development of AAC. More diverse research is needed, including various disabilities and higher-technology AAC tools. The effectiveness of AAC in impacting users and their communication partners will increase their quality of life and social interactions.

Background: Preadolescents, who are in a transitional phase of development, may experience higher exposure to heterosexual interactions while facing higher risks regarding misinformation in sexual knowledge and unsafe engagement in sexual activities. There is a deficiency in the availability of qualified educators and age-appropriate teaching materials for sexuality education in China. Methods: We implemented an animation-based comprehensive sexuality education package among preadolescents aged 9 to 12 years from eight schools in Anhui, China. The first round of intervention included 1,835 participants, lasting 2 months from September to November 2020. A total of 374 participants, accounting for 52% of the intervention group, received a second round of intervention in September 2021. Participants completed immediate follow-up assessment and 1-year follow-up assessment to assess changes in their sexual knowledge, attitudes, and other outcomes. Propensity score matching and difference-in-difference analysis were performed to determine the short- and long-term impacts. Results: Significant improvements were observed for both sexual knowledge and sexual attitudes in the immediate follow-up. There was no significant effect on pornography-seeking behavior or awareness of experiencing sexual abuse. After 1 year, the effect was sustained for sexual knowledge, but slightly declined for sexual attitudes. The second intervention significantly improved sexual knowledge; however, no significant change in sexual attitudes, pornography-seeking behavior, or awareness of experiencing sexual abuse was observed. Conclusions: Our comprehensive sexuality education package was effective in improving sexual knowledge both immediately and 1 year after the intervention. Repeated intervention can be an effective strategy for promoting preadolescent health development regarding comprehensive sexuality education.

Collaborative Problem Solving (CPS) has received increasing attention for its role in promoting learners' cognitive and social development in STEM education. However, little is known about how learners interact dynamically within a group at different time granularities. This gap mainly resulted from overlooking the time dimension of interactions, leading to a lack of nuanced understanding of moment-to-moment interaction in CPS. In this study, we demonstrated the potential of "temporal group interaction density" in modeling online CPS interactions and investigated the impact of temporal interaction density on CPS processes and outcomes. Specifically, we proposed using cumulative weighted density to measure the holistic state of group interactions and explained the differences in group interactions with different collaborative performance and interaction densities by modeling the transition and evolution of interaction sequences through Apriori and cumulative relative centrality. Results indicated that group interaction density cannot directly predict their collaborative performance, but notable differences in interaction patterns existed in the high-performance groups with different interaction densities, while low-performance groups showed interactive commonalities towards the completion of CPS. The findings of this study guided the design of CPS interventions and supported the process mining of CPS interactions, with vital practical implications for CPS assessment and skills development.

Tools for rapid identification of novel and/or emerging viruses are urgently needed for clinical diagnosis of unexplained infections and pandemic preparedness. Here we developed and clinically validated a largely automated metagenomic next-generation sequencing (mNGS) assay for agnostic detection of respiratory viral pathogens from upper respiratory swab and bronchoalveolar lavage samples in

Humans are exposed to DNA alkylating agents through endogenous metabolism, environmental exposure and cancer chemotherapy. The resulting alkylated DNA adducts may elicit genome instability by perturbing DNA replication and transcription. R-loops regulate various cellular processes, including transcription, DNA repair, and telomere maintenance. However, unscheduled R-loops are also recognized as potential sources of DNA damage and genome instability. In this study, by employing fluorescence microscopy and R-loop sequencing approaches, we uncovered, for the first time, that minor-groove N2-alkyl-dG lesions elicit elevated R-loop accumulation in chromatin and in plasmid DNA in cells. We also demonstrated that the N2-alkyl-dG-induced R-loops impede transcription elongation and compromise genome integrity. Moreover, genetic depletion of DDX23, a R-loop helicase, renders cells more sensitive toward benzo[a]pyrene diolepoxide, a carcinogen that induces mainly the minor-groove N2-dG adduct. Together, our work unveiled that unrepaired minor-groove N2-alkyl-dG lesions may perturb genome integrity through augmenting R-loop levels in chromatin. Our findings suggest a potential therapeutic strategy involving the combination of R-loop helicase inhibitors with DNA alkylating drugs.

Healthcare facilities produce millions of tons of waste annually, with a significant portion consisting of diagnostic plasticware. Here, we introduce a new detection platform that completely replaces traditional assay plates with a piece of membrane, offering a much greener and more sustainable alternative. The membrane, integrated within the portable vortex fluidic device (P-VFD), enables rapid detection of a clinically relevant protein biomarker, urinary p75ECD. This biomarker is utilized to evaluate the prognosis, disease severity, and progression of amyotrophic lateral sclerosis (ALS). This assay has a limit-of-detection (LOD) of 4.03 pg, which is comparable to the plate-based assay (2.24 pg) and has been optimised through a full factorial design of experiments (DOE) and response surface methodology (RSM). P-VFD has great potential in quantifying p75ECD in human biofluids and can significantly reduce the assay time to 5 min compared to the current plate-based p75ECD ELISA assay (3 days), with at least a 4.4-fold reduction in the usage of the detection antibody.

Condensation of RNA and proteins is central to cellular functions, and the ability to program it would be valuable in synthetic biology and synthetic cell science. Here we introduce a modular platform for engineering synthetic RNA condensates from tailor-made, branched RNA nanostructures that fold and assemble co-transcriptionally. Up to three orthogonal condensates can form simultaneously and selectively accumulate fluorophores through embedded fluorescent light-up aptamers. The RNA condensates can be expressed within synthetic cells to produce membrane-less organelles with a controlled number and relative size, and showing the ability to capture proteins using selective protein-binding aptamers. The affinity between otherwise orthogonal nanostructures can be modulated by introducing dedicated linker constructs, enabling the production of bi-phasic RNA condensates with a prescribed degree of interphase mixing and diverse morphologies. The in situ expression of programmable RNA condensates could underpin the spatial organization of functionalities in both biological and synthetic cells.

Psoriasis, an immune-mediated inflammatory skin disorder characterized by a chronically relapsing-remitting course, continues to be primarily managed through topical therapy. While oral administration of tyrosine kinase 2 inhibitors (TYK2i) stands as an effective approach for psoriasis treatment, the potential efficacy of topical application of TYK2i remains unexplored. Herein, the carbomer/alginic acid hydrogel is embedded with borneol (BO) as a new topical carrier of TYK2i for achieving enhanced transdermal permeation and anti-psoriasis efficacy. The hydrogel system, i.e., TYK2i-BO-gel, exhibits significantly improved preventative and therapeutic effects in mice models of psoriasiform dermatitis, as evidenced by phenotypical images, psoriasis severity score index (PSI), histology, immunohistochemical staining, and PCR analysis. Remarkably, TYK2i-BO-gel outperforms conventional topical corticosteroid therapy by significantly preventing psoriatic lesion recurrence as measured by a nearly 50 % reduction in ear thickness changes (p

Starting in the 1970s, individuals, businesses and the public have increasingly benefited from policies prohibiting smoking indoors, saving thousands of lives and billions of dollars in healthcare expenditures. Smokefree policies to protect against secondhand smoke exposure, however, do not fully protect the public from the persistent and toxic chemical residues from tobacco smoke (also known as thirdhand smoke) that linger in indoor environments for years after smoking stops. Nor do these policies address the economic costs that individuals, businesses and the public bear in their attempts to remediate this toxic residue. We discuss policy-relevant differences between secondhand smoke and thirdhand smoke exposure: persistent pollutant reservoirs, pollutant transport, routes of exposure, the time gap between initial cause and effect, and remediation and disposal. We examine four policy considerations to better protect the public from involuntary exposure to tobacco smoke pollutants from all sources. We call for (a) redefining smokefree as free of tobacco smoke pollutants from secondhand and thirdhand smoke; (b) eliminating exemptions to comprehensive smoking bans; (c) identifying indoor environments with significant thirdhand smoke reservoirs; and (d) remediating thirdhand smoke. We use the case of California as an example of how secondhand smoke-protective laws may be strengthened to encompass thirdhand smoke protections. The health risks and economic costs of thirdhand smoke require that smokefree policies, environmental protections, real estate and rental disclosure policies, tenant protections, and consumer protection laws be strengthened to ensure that the public is fully protected from and informed about the risks of thirdhand smoke exposure.

Cancer stem cells, characterized by high tumorigenicity and drug-resistance, are often responsible for tumor progression and metastasis. Aldehyde dehydrogenases, often overexpressed in cancer stem cells enriched tumors, present a potential target for specific anti-cancer stem cells treatment. In this study, we report a self-assembled nano-prodrug composed of aldehyde dehydrogenases activatable photosensitizer and disulfide-linked all-trans retinoic acid for diagnosis and targeted treatment of cancer stem cells enriched tumors. The disulfide-linked all-trans retinoic acid can load with photosensitizer and self-assemble into a stable nano-prodrug, which can be disassembled into all-trans retinoic acid and photosensitizer in cancer stem cells by high level of glutathione. As for the released photosensitizer, overexpressed aldehyde dehydrogenase catalyzes the oxidation of aldehydes to carboxyl under cancer stem cells enriched microenvironment, activating the generation of reactive oxygen species and fluorescence emission. This generation of reactive oxygen species leads to direct killing of cancer stem cells and is accompanied by a noticeable fluorescence enhancement for real-time monitoring of the cancer stem cells enriched microenvironment. Moreover, the released all-trans retinoic acid, as a differentiation agent, reduce the cancer stem cells stemness and improve the cancer stem cells enriched microenvironment, offering a synergistic effect for enhanced anti-cancer stem cells treatment of photosensitizer in inhibition of in vivo tumor growth and metastasis.

BackgroundCOVID-19 is associated with acute risk of major adverse cardiac events (MACE), including myocardial infarction, stroke, and mortality (all-cause). However, the duration and underlying determinants of heightened risk of cardiovascular disease and MACE post-COVID-19 are not known.MethodsData from the UK Biobank was used to identify COVID-19 cases (n=10 005) who were positive for polymerase chain reaction (PCR+)-based tests for SARS-CoV-2 infection (n=8062) or received hospital-based International Classification of Diseases version-10 (ICD-10) codes for COVID-19 (n=1943) between February 1, 2020 and December 31, 2020. Population controls (n=217 730) and propensity score-matched controls (n=38 860) were also drawn from the UK Biobank during the same period. Proportional hazard models were used to evaluate COVID-19 for association with long-term (>1000 days) risk of MACE and as a coronary artery disease risk equivalent. Additional analyses examined whether COVID-19 interacted with genetic determinants to affect the risk of MACE and its components.ResultsThe risk of MACE was elevated in COVID-19 cases at all levels of severity (HR, 2.09 [95% CI, 1.94-2.25]; P

Rosacea is a chronic inflammatory skin disorder, whose underlying cellular and molecular mechanisms remain obscure. Here, we generate a single-cell atlas of facial skin from female rosacea patients and healthy individuals. Among keratinocytes, a subpopulation characterized by IFNγ-mediated barrier function damage is found to be unique to rosacea lesions. Blocking IFNγ signaling alleviates rosacea-like phenotypes and skin barrier damage in mice. The papulopustular rosacea is featured by expansion of pro-inflammatory fibroblasts, Schwann, endothelial and macrophage/dendritic cells. The frequencies of type 1/17 and skin-resident memory T cells are increased, and vascular mural cells are characterized by activation of inflammatory pathways and impaired muscle contraction function in rosacea. Most importantly, fibroblasts are identified as the leading cell type producing pro-inflammatory and vasodilative signals in rosacea. Depletion of fibroblasts or knockdown of PTGDS, a gene specifically upregulated in fibroblasts, blocks rosacea development in mice. Our study provides a comprehensive understanding of the aberrant alterations of skin-resident cell populations and identifies fibroblasts as a key determinant in rosacea development.

ImportanceGuideline-directed medical therapy (GDMT) remains underutilized on a global level, with significant disparities in access to treatment worldwide. The potential global benefits of quadruple therapy on patients with heart failure with reduced ejection fraction (HFrEF) have not yet been estimated.ObjectiveTo assess the projected population-level benefit of optimal GDMT use globally among patients with HFrEF.Design, setting, and participantsEstimates for HFrEF prevalence, contraindications to GDMT, treatment rates, and the number needed to treat for all-cause mortality at 12 months were derived from previously published sources. Potential lives saved from optimal implementation of quadruple therapy among patients with HFrEF was calculated globally and a sensitivity analysis was conducted to account for uncertainty in the existing data.Main outcomes and measuresAll-cause mortality.ResultsOf an estimated 28.89 million people with HFrEF worldwide, there were 8 235 063 (95% CI, 6 296 020-10 762 972) potentially eligible for but not receiving β-blockers, 20 387 000 (95% CI, 15 867 004-26 184 996) eligible for but not receiving angiotensin receptor-neprilysin inhibitors, 12 223 700 (95% CI, 9 376 895-15 924 973) eligible for but not receiving mineralocorticoid receptor antagonists, and 21 229 170 (95% CI, 16 537 400-27 242 688) eligible for but not receiving sodium glucose cotransporter-2 inhibitors. Optimal implementation of quadruple GDMT could potentially prevent 1 188 277 (95% CI, 767 933-1 914 561) deaths over 12 months. A large proportion of deaths averted were projected in Southeast Asia, Eastern Mediterranean and Africa, and the Western Pacific regions.Conclusions and relevanceImprovement in use of GDMT could result in substantial mortality benefits on a global scale. Significant heterogeneity also exists across regions, which warrants additional study with interventions tailored to country-level differences for optimization of GDMT worldwide.

A breast cancer risk assessment tool for Asian populations, incorporating Polygenic Risk Score and Gail Model algorithm, has been established and validated. However, effective methods for delivering personalized risk information remain underexplored. This study aims to identify and develop effective methods for conveying breast cancer risk information to Asian women. Through ten focus group discussions with 32 women in Indonesia and Singapore, we explored preferences for the presentation of risk information. Participants favored comprehensive reports featuring actionable steps, simplified language, non-intimidating visuals, and personalized risk reduction recommendations. Singaporean participants, more aware of breast cancer prevention, showed a lower likelihood of seeking follow-ups upon receiving low-risk results compared to Indonesians. Overall, participants found the reports useful and advocated for similar approaches in other disease assessments. Balancing content and complexity in reports is crucial, highlighting the need for improved patient understanding and engagement with healthcare providers. Future studies could explore physicians roles in delivering personalized risk assessments for breast cancer prevention.

PurposeHigh consumption of fruits and vegetables decrease the risk of bladder cancer (BC). The evidence of specific fruits and vegetables and the BC risk is still limited.MethodsFruit and vegetable consumptions in relation to BC risk was examined by pooling individual participant data from case-control studies. Unconditional logistic regression was used to estimate study-specific odds ratio's (ORs) with 95% confidence intervals (CIs) and combined using a random-effects model for intakes of total fruits, total vegetables, and subgroups of fruits and vegetables.ResultsA total of 11 case-control studies were included, comprising 5637 BC cases and 10,504 controls. Overall, participants with the highest intakes versus the lowest intakes of fruits in total (OR 0.79; 95% CI 0.68-0.91), citrus fruits (OR 0.81; 95% CI 0.65-0.98), pome fruits (OR 0.76; 95% CI 0.65-0.87), and tropical fruits (OR 0.84; 95% CI 0.73-0.94) reduced the BC risk. Greater consumption of vegetables in total, and specifically shoot vegetables, was associated with decreased BC risk (OR 0.82; 95% CI 0.68-0.96 and OR 0.87; 95% CI 0.78-0.96, respectively). Substantial heterogeneity was observed for the associations between citrus fruits and total vegetables and BC risk.ConclusionThis comprehensive study provides compelling evidence that the consumption of fruits overall, citrus fruits, pome fruits and tropical fruits reduce the BC risk. Besides, evidence was found for an inverse association between total vegetables and shoot vegetables intake.

UNLABELLED: A common complication of chimeric antigen receptor (CAR) T-cell therapy is immune effector cell-associated neurotoxicity syndrome (ICANS), which presents with encephalopathy, aphasia, inattention, somnolence, seizures, weakness, or cerebral edema. Despite its significant morbidity, there are currently no effective targeted treatments. Given the clinical similarities between ICANS and the neurological manifestations of acute hypophosphatemia, we retrospectively reviewed 499 patients treated with CD19-targeted CAR T-cell therapy across multiple clinical trials between 2015 and 2020. In addition to clinical toxicities experienced by the patients, we also interrogated the impact of serum electrolyte data and repletion of corresponding electrolyte deficiencies with ICANS incidence, severity, and duration. Hypophosphatemia was a common occurrence in CAR T-cell recipients and the only electrolyte derangement associated with a significantly higher cumulative incidence of ICANS. Moreover, phosphorus repletion in patients with hypophosphatemia was associated with significantly decreased ICANS incidence and duration. Hypophosphatemia was uniquely associated with encephalopathy neurological adverse events, which also showed the strongest positive correlation with both ICANS and cytokine release syndrome severity. These findings suggest that serum phosphorus could be a reliable biomarker for ICANS, and expeditious, goal-directed phosphorus repletion in response to serum hypophosphatemia could be a safe, inexpensive, and widely available intervention for such patients. SIGNIFICANCE: Herein we show that phosphorus repletion in patients with hypophosphatemia receiving anti-CD19 chimeric antigen receptor T-cell therapeutics was associated with significantly decreased immune effector cell-associated neurotoxicity syndrome (ICANS) incidence and symptom duration. Given the significant morbidity associated with ICANS and lack of targeted interventions, hypophosphatemia may serve as both a useful biomarker and an inexpensive intervention for ICANS.

BackgroundVentricular ablation may be clinically indicated for patients with recurrent ventricular tachycardia (VT) and has been shown to decrease risk of recurrence and overall morbidity. However, the existence of disparities among patients receiving ventricular ablation has not been well characterized.ObjectivesIn this study, the authors examined patients hospitalized with VT to determine whether disparities exist among those receiving ablations.MethodsThe authors used the National Inpatient Sample to assess patients hospitalized with a primary diagnosis of VT in 2019 who did and did not receive catheter ablations. Multiple logistic regression was used to calculate risk factors for VT ablation based on age, sex, race/ethnicity, socioeconomic status, and hospital characteristics.ResultsAfter adjusting for baseline characteristics and comorbidities, female and Black patients hospitalized with VT had significantly lower odds of receiving ablations compared with male and White patients (OR: 0.835; 95% CI: 0.699-0.997; P = 0.047; and OR: 0.617; 95% CI: 0.457-0.832; P = 0.002, respectively). Additionally, patients at rural or nonteaching hospitals were significantly less likely to receive ablations compared with those at urban, teaching hospitals. No significant differences were noted based on income or insurance status in the adjusted models.ConclusionsThe authors identified significant disparities in the delivery of ventricular ablations among patients hospitalized with VT. Overall, patients who were female or Black as well as those who were hospitalized at rural or nonteaching hospitals were significantly less likely to receive VT ablations during hospitalization.

TGF-β, essential for development and immunity, is expressed as a latent complex (L-TGF-β) non-covalently associated with its prodomain and presented on immune cell surfaces by covalent association with GARP. Binding to integrin αvβ8 activates L-TGF-β1/GARP. The dogma is that mature TGF-β must physically dissociate from L-TGF-β1 for signaling to occur. Our previous studies discovered that αvβ8-mediated TGF-β autocrine signaling can occur without TGF-β1 release from its latent form. Here, we show that mice engineered to express TGF-β1 that cannot release from L-TGF-β1 survive without early lethal tissue inflammation, unlike those with TGF-β1 deficiency. Combining cryogenic electron microscopy with cell-based assays, we reveal a dynamic allosteric mechanism of autocrine TGF-β1 signaling without release where αvβ8 binding redistributes the intrinsic flexibility of L-TGF-β1 to expose TGF-β1 to its receptors. Dynamic allostery explains the TGF-β3 latency/activation mechanism and why TGF-β3 functions distinctly from TGF-β1, suggesting that it broadly applies to other flexible cell surface receptor/ligand systems.

PURPOSE OF REVIEW: In this review, we discuss the status of novel radiation shielding and other methods to reduce radiation exposure and its associated health risks within the CCL. RECENT FINDINGS: There are many devices on the market each with its unique advantages and inherent flaws. Several are available for widespread use with promising data, while others still in development. The field of percutaneous transcatheter interventions includes complex procedures often involving significant radiation exposure. Increased radiation exposes the proceduralist and CCL staff to potential harm from both direct effects of radiation but also from the ergonomic consequences of daily use of heavy personal protective equipment. Here we discuss several innovative efforts to reduce both radiation exposure and orthopedic injury within the CCL that are available, leading to a safer daily routine in a lead [apron]-free environment.