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Microorganisms are ubiquitous in nature and are central to human, animal, environmental, and planetary health. They play a particularly important role in the food chain and the production of high-quality, safe, and health-promoting foods, especially fermented foods. This important role is not always apparent to members of the public. Here, we describe Kefir4All, a citizen science project designed to provide the general public with an opportunity to expand their awareness, knowledge, and practical skills relating to microbiology, introduced through the medium of producing fermented food, i.e., milk kefir or water kefir. During the course of Kefir4All, 123 citizen scientists, from second-level school and non-school settings, participated in a study to track changes in the microbial composition of kefirs, by performing and recording details of milk kefir or water kefir fermentations they performed in their homes or schools over the21-week project. At the start of the study, the citizen scientists were provided with milk or water kefir grains to initiate the fermentations. Both types of kefir grain are semi-solid, gelatinous-like substances, composed of exopolysaccharides and proteins, containing a symbiotic community of bacteria and yeast. The experimental component of the project was complemented by a number of education and outreach events, including career talks and a site visit to our research center (Kefir Day). At the end of the study, a report was provided to each citizen scientist, in which individualized results of their fermenting activities were detailed. A number of approaches were taken to obtain feedback and other insights from the citizen scientists. Evaluations took place before and after theKefir4All project to gauge the citizen scientist's self-reported awareness, knowledge, and interest in microbiology and fermented foods. Further insights into the level of citizen science participation were gained through assessing the number of samples returned for analysis and the level of participation of the citizen scientists throughout the project. Notably, the survey results revealed a self-reported, increased interest in, and general knowledge of, science among the Kefir4All citizen scientists after undertaking the project and a willingness to take part in further citizen science projects. Ultimately, Kefir4Allrepresents an example of the successful integration of citizen science into existing education and research systems.

PurposeThe purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC).Experimental designRB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 patients with primary HGSC to characterize tumors with concurrent BRCA deficiency and RB1 loss.ResultsRB1 loss was associated with longer OS in HGSC but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared with patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA deficiency correlated with transcriptional markers of enhanced IFN response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1.ConclusionsCo-occurrence of RB1 loss and BRCA deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.

Abstract: Lyman break galaxies (LBGs) are promising probes for clustering measurements at high redshift, z > 2, a region only covered so far by Lyman-α forest measurements. In this paper, we investigate the feasibility of selecting LBGs by exploiting the existence of a strong deficit of flux shortward of the Lyman limit, due to various absorption processes along the line of sight. The target selection relies on deep imaging data from the HSC and CLAUDS surveys in the g, r, z and u bands, respectively, with median depths reaching 27 AB in all bands. The selections were validated by several dedicated spectroscopic observation campaigns with DESI. Visual inspection of spectra has enabled us to develop an automated spectroscopic typing and redshift estimation algorithm specific to LBGs. Based on these data and tools, we assess the efficiency and purity of target selections optimised for different purposes. Selections providing a wide redshift coverage retain 57% of the observed targets after spectroscopic confirmation with DESI, and provide an efficiency for LBGs of 83±3%, for a purity of the selected LBG sample of 90±2%. This would deliver a confirmed LBG density of ~ 620 deg-2 in the range 2.3 < z < 3.5 for a r-band limiting magnitude r < 24.2. Selections optimised for high redshift efficiency retain 73% of the observed targets after spectroscopic confirmation, with 89±4% efficiency for 97±2% purity. This would provide a confirmed LBG density of ~ 470 deg-2 in the range 2.8 < z < 3.5 for a r-band limiting magnitude r < 24.5. A preliminary study of the LBG sample 3d-clustering properties is also presented and used to estimate the LBG linear bias. A value of b LBG = 3.3 ± 0.2  (stat.) is obtained for a mean redshift of 2.9 and a limiting magnitude in r of 24.2, in agreement with results reported in the literature.

With the rising demand for virtual learning, districts are establishing virtual schools to offer more flexible education. This study investigates K-12 virtual learner characteristics, examines trends and issues in virtual academies, and outlines opportunities and challenges faced by stakeholders in a southeastern U.S. state. The study used a mixed-method design, combining quantitative survey data and qualitative interviews with virtual academy leaders. Results reveal that virtual learners opt for this mode of schooling due to busy extracurricular schedules, a desire to avoid crowded schools or health concerns. These students include those with special needs and high-achieving individuals. Collaboration between parents and teachers plays a crucial role. Essential factors include reliable internet access, teacher tech proficiency, and diverse curriculum development approaches. However, diverse curricular methods require additional implementation support. Balancing instructional flexibility with accountability poses a significant challenge. Virtual teachers need resources, professional development, and time, especially when transitioning from traditional to digital curriculum. Effective communication and interpersonal interactions are vital. Involving home learning coaches and community partnerships enhances the educational experience. While virtual schools offer flexible and personalized support, they encounter challenges related to resource access, social isolation, and student motivation.

The study focuses on the identification of relationships and/or rules between computational thinking (CT) concepts among the undergraduate students of Applied Informatics due to their attitudes towards mathematics. We analyze three CT concepts -- decomposition, pattern recognition, and algorithmic thinking. We assume that students who have a closer relationship with mathematics, a positive attitude towards mathematics, have better developed CT. We conducted the experiment during the 2022/2023 academic year on the Information Coding and Displaying subject. The results indicate that those students who have no relationship to mathematics, negative attitude towards mathematics, have no problem with decomposition and pattern recognition, but without significant algorithmic thinking. On the other hand, students who have a close relationship with mathematics are also able to decompose or recognize patterns, but moreover they have shown algorithmic thinking. The contribution of the study comprises the identification of relationships and/or patterns of computational thinking concepts among students who have a relationship to mathematics, who cannot assess their relationship to mathematics, as well as among students who have no relationship to mathematics. Our results indicate a different occurrence of computational thinking concepts as well as links and/or relationships between them.

Since stepping into education delivery, technology continues to revolutionise education, responding to access and equity. This has made online learning to be the choice for access and equity like never seen before. Unfortunately, it has not only provided solutions but also introduced issues that have created the divide in technology and online learning for learners and institutions. The study explored online learning in the Solomon Islands from students' narratives at the Solomon Islands National University via "tok stori"; seeking to understand what they perceived as enablers and barriers of online learning. The study employed the sequential mixed-method approach and was guided by the theories of transactional distance and interaction, with the latter's extensions. The findings show that the level and strategies of support in administration, academics, and technology determine what transpires as an enabler or a barrier to online learning.

The Diversity in Science towards Social Inclusion--Non-formal Education in Science for Students' Diversity (DiSSI) project aimed to provide a holistic perspective on diversity, focusing specifically on cultural and ethnic identities, language, socioeconomic background, gender, as well as differing levels of achievement. In particular, the work presented in this paper aims to tackle consciously the issues surrounding teaching and learning in socio-economically deprived areas through non-formal education. This paper presents the results of a pilot study that examined how students participating in non-formal education engage with multi-modal pedagogical approaches designed to address multiple dimensions of diversity via an intersectionality lens. Working with diverse groups requires varied methods; as such, a mixed-method approach was employed in the study to ensure the research team authentically captured and engaged with the lived experiences of the participants. The study aimed to generate best practices that augment the science capital of students, which are applicable across various contexts of diversity. The pedagogical approaches, while not novel in science education literature, were rarely utilised by the teacher and thus were rarely experienced by the students. Participants reported a greater sense of autonomy and ownership of the science through participation in the DiSSI programme. Preliminary results indicate an overall positive experience for students and teachers alike and offer insights into the overall lived experiences of participants, which inform future work.

This research explores the implementation of Arabic language learning at the Maitreechit Withayattan School in Bangkok, Thailand. With a population dominated by a Muslim minority, this research aims to understand the challenges and potential for developing Arabic language education in this context. The research background reflects Thailand's uniqueness as an ASEAN country with a Muslim minority that is recognized and regulated by national law. The focus of the research is on issues of student interest, teaching methods, hidden learning goals, and the role of teachers in the learning process. The research method uses modern ethnographic studies at Maitrechit Wittaayathan School Bangkok. Research findings show that students' low interest is influenced by less innovative teaching methods and a need for more variety in learning. Hidden learning goals, which include students' political aspirations to support the position of Muslims in government, become a complex dynamic in Arabic language learning. The importance of Arabic in the government context was a significant finding, with students being taught that Arabic language skills can provide a competitive advantage in careers in the government sector. Despite challenges regarding student interest, school administrators' high enthusiasm for Arabic creates the potential for solid collaboration between education and religious identity development. Implications for Arabic language education management include the need for more exciting learning strategies, teacher training, and collaboration with external parties to increase the relevance of learning to careers. This research provides in-depth insight into the complex dynamics of Arabic language education in Muslim minority school environments in Thailand. However, it should be acknowledged that the research findings are limited to one school in Bangkok, and generalization of the findings must be done cautiously.

In a challenging world, the spotlight on children's wellbeing has strengthened. There is extensive research about the ways in which well-designed arts education programs positively impact children's wellbeing. Despite this, arts education continues to be marginalised in schools. When researchers with arts education and leadership experience teamed up to consider the intransient nature of the resistance to arts education in primary/elementary schools, they conducted a collaborative autoethnography (CAE) to see if this offered new insights. The iterative process of sharing and interrogating personal stories to distil collective meanings (themes) highlighted four features of education programs that provide sustained support for children's wellbeing: centering in a discordant world; effective leadership; experiential processes, engagement, and trust; and harnessing the transformative potential of the arts. The CAE also pointed the team towards conducting future inquiries about the currently under-researched role of the school principal in instigating cultural change that sustains meaningful arts education.

Social networks have grown rapidly in recent years, enabling the application of social web technologies to the scientific process and creating platforms that enhance communication between researchers. The aim of this research is to go one step further and investigate whether the use of more general social networks, such as Twitter (currently X) or Facebook, is also becoming more widespread for scientific research, thus contributing to the visibility of scientists and their collaborative networks. Social media analysis is carried out using the Brandwatch platform to assess the use of generalist social networks in research, and compared with the use of scientific social networks through an online survey of university professors. The resulting conclusions show that scientific mentions in networks are rare and that, despite the importance of researchers having a profile in a social network, which allows them to give greater visibility to their results and receive feedback from their colleagues, many of them are still unaware of its usefulness.

As part of a large exercise physiology laboratory (lab) reform project, we used blended learning to support graduate teaching assistants and lab technicians in developing their pedagogical knowledge and create an entry point to reflective conversations about teaching and learning. Because self-paced asynchronous online modules can enable reflective and self-determined learning, this asynchronous professional development course is punctuated with reflective questions for the instructional team preparing to teach reformed exercise physiology labs. Asynchronous course content was shared via short videos, podcasts, and readings. We debriefed this self-paced, SoTL-informed course together, in-person. This social debriefing kicked off our weekly synchronous reflective conversations about teaching and learning in a community of practice. Developing a shared language for talking about teaching, enabling student learning, practicing effective teaching, and beginning to contemplate teaching philosophies were described by graduate teaching assistants as notable aspects of this blended learning journey. Lab technicians described discovering SoTL and discussing learning challenges as helpful to their teaching. [Articles in this journal were presented at the University of Calgary Conference on Postsecondary Learning and Teaching.]

During the COVID pandemic, universities around the globe had to move not only their content delivery online, but also their assessments. Due to COVID causing significant upheaval in Higher Education (HE), this enforced experiment also afforded an opportunity to reflect on traditional, invigilated, closed book exams (ICBE) resulting in research and advice in this area. A systematic review of this academic and grey literature was performed concentrating on maths heavy physics examinations to investigate what guidance is given to examination writers, educators who prepare students for exams and HE examinees themselves. The literature review results were divided into: Advice for examiners who need to provide an uinvigilated open book exam (UOBE), discussions on cheating, advice for students and case studies. It was found that ICBEs were good at examining lower order cognitive skills, e.g. recall and understanding, but higher order skills, such as analysing and synthesising, are better examined with access to a larger range of resources. Guidance on making academic misconduct more difficult also suggested using higher order thinking skills in exam questions as responses to these types of tasks are more individual and getting outside help may be more difficult in a time constrained UOBE. Furthermore, literature encouraged reflection on the motivation for cheating and suggested that overly demanding assessment may encourage students to seek inappropriate help. The advice for students highlighted the need to prepare as thoroughly for a UOBE as they would for a traditional exam. Probably the thrust should change from pure memorization to students preparing their notes so that they can efficiently access their material to locate relevant parts for synthesis during a UOBE. Some of the case studies used statistical methods to investigate comparability of grades between UOBEs and ICBEs and some of the studies found them comparable, so a large shift of results may be due to other factors rather than the exam type. Other studies describe their approach and include stakeholder reflections. The main recommendation to exclude lower cognitive skills can pose a problem for maths heavy exams as they mainly assess how well an examinee has mastered these skills before building on them. However, it seems advisable to climb higher up Bloom's taxonomy if possible. Also, it may be conceivable to break up exams into shorter sections that require individual uploading before access to the next part is granted to reduce the possibility of outside help. Furthermore, individualised maths type problems could be achievable by using different data sets for a question. Student advice should highlight the differences between UOBEs and ICBEs so that they can prepare appropriately.

Bichronous online learning is the intentional blending of asynchronous and synchronous online learning experiences. Twelve award-winning online instructors participated in interviews to discuss best practices they use, and benefits and challenges in bichronous online courses. When sharing best practices for bichronous online courses, online instructors explained how they combined best practices in asynchronous and synchronous online learning. Asynchronous online best practices included course design and structure, resources, and instructor presence; and synchronous online best practices focused on formats, activities, and content of synchronous sessions, and community-building. The best practices, benefits and challenges discussed in this paper have implications for instructors who currently teach in a bichronous online format or may be considering it in the future, and for instructional designers and administrators who work with faculty on offering courses in this modality. Based on the data, the intentional blending of synchronous and asynchronous components has a lot of potential to enhance students' online learning experiences.

The benefits of afterschool activity participation for youth development are well-documented. An interesting question dominating this field is whether there is a threshold at which point participating in too many activities (breadth) and spending too much time in those activities (intensity) is negatively associated with desirable outcomes. Using 9th grade student data (N=115,731) from three administrations of a state-wide school survey, we explore whether students' breadth and intensity of afterschool participation is associated with GPA and perceived family and community support. Findings corroborate prior research in demonstrating the association between breadth and intensity. Importantly, we extend the discussion, with three important observations. First, a linear model is insufficient for modeling these complex associations with outcomes. Second, there is a threshold at which too much participation has a negative impact in these outcomes. Third, variations in activities, time windows and indices have small or no influence in the association with outcomes.

Background: Like other professional training programs, social work pedagogy has long recognized the value of experiential learning for professional development. Despite social work's rich experiential learning literature involving field education, direct practice courses, and program evaluation, there is a dearth of literature examining how to make learning in the policy classroom experiential, particularly for large class sizes. Purpose: We asked, "How might electoral candidate debates provide experiential learning opportunities for large classes?" Approach: The authors organized municipal and federal election candidate debates attended in-person and online by over 300 undergraduate students in a social work policy class at a Canadian university. Integrating our experiences as instructors/organizers and a teaching assistant, within a social constructivist framework, we used Kolb's experiential learning theory, and critiques thereof, to analyze reflective assignments from 73 students. Results and Conclusions: Candidate debates, when facilitated appropriately, can encourage students in large courses to work through the stages of experiential learning and consider related concepts and possible links among social justice course content and social policy, social work practice, and political engagement. Implications: The paper contributes to a broader understanding of the opportunities and constraints associated with employing experiential learning in the large social work classroom and beyond.

Cultural comparisons suggest that an understanding of other minds may develop sooner in independent versus interdependent settings, and vice versa for inhibitory control. From a western lens, this pattern might be considered paradoxical, since there is a robust positive relationship between theory of mind (ToM) and inhibitory control in western samples. In independent cultures, an emphasis on one's own mind offers a clear route to 'simulate' other minds, and inhibitory control may be required to set aside one's own perspective to represent the perspective of others. However, in interdependent cultures, social norms are considered the key catalyst for behaviour, and metacognitive reflection and/or suppression of one's own perspective may not be necessary. The cross-cultural generalizability of the western developmental route to ToM is therefore questionable. The current study used an age-matched cross-sectional sample to contrast 56 Japanese and 56 Scottish 3-6-year-old's metacognition, ToM and inhibitory control skills. We replicated the expected cultural patterns for ToM (Scotland > Japan) and inhibitory control (Japan > Scotland). Supporting western developmental enrichment theories, we find that inhibitory control and metacognition predict theory of mind competence in Scotland. However, these variables cannot be used to predict Japanese ToM. This confirms that individualistic mechanisms do not capture the developmental mechanism underlying ToM in Japan, highlighting a bias in our understanding of ToM development.

The current study investigated perfectionism and procrastination from the trait and cognitive perspectives and addressed how they relate to components of a personal orientation toward failure. A sample of 327 undergraduate students completed three perfectionism measures (i.e., Frost Multidimensional Perfectionism Scale, Hewitt-Flett Multidimensional Perfectionism Scale, and Perfectionism Cognitions Inventory), two procrastination measures (i.e., Lay Procrastination Scale and Procrastinatory Cognitions Inventory), and measures of fear of failure and overgeneralizing failure. Correlational analyses showed that the composite trait dimension of perfectionistic concerns and the cognitive dimension of perfectionistic automatic thoughts had modest links with trait procrastination but much stronger links with the cognitive measure of procrastinatory automatic thoughts. All perfectionism and procrastination measures were significantly correlated with fear of failure and overgeneralization of failure. More extensive analyses showed that fear of failure mediated trait and cognitive pathways between perfectionism and procrastination, and the overgeneralization of failure mediated most pathways. Other evidence supported a sequential mediation between perfectionism and procrastination (i.e., fear of failure followed by the overgeneralization of failure). Overall, the results suggest that procrastinating perfectionists have a cognitive hypersensitivity to failure and a potentially debilitating form of perfectionistic reactivity characterized by overgeneralizing failures to the self. The theoretical and practical implications are discussed.

The Perfectionism Social Disconnection Model (PSDM) and the Existential Model of Perfectionism and Depressive Symptoms (EMPDS) are promising models of perfectionism and psychopathology. However, research examining suicide ideation within the PSDM is scarce, and no research has examined suicide ideation as an outcome in the EMPDS. Moreover, tests of the PSDM and EMPDS have been conducted separately and most research has examined the PSDM and EMPDS using cross-sectional or two-wave longitudinal designs, which do not provide a satisfactory test of mediation. In the current study, we addressed these limitations by testing whether perfectionism confers vulnerability to suicide ideation via feelings of mattering and anti-mattering (from the PSDM) and via difficulty accepting the past (from the EMPDS) in a three-wave longitudinal design in two independent samples of undergraduate students and community adults. Participants completed measures on three occasions over 6 weeks. Findings revealed that socially prescribed perfectionism indirectly predicted suicide ideation via difficulty accepting the past in both samples. In addition, in the undergraduate sample only, socially prescribed perfectionism indirectly predicted higher suicide ideation via anti-mattering, and self-oriented perfectionism indirectly predicted higher suicide ideation via mattering. Based on our findings, we advocate for future research to include suicide ideation in the PSDM and EMPDS, to integrate explanatory models, and to examine a mattering-specific EMPDS.

Friendships are important for the mental well-being of emerging adults. Socially prescribed perfectionism, where individuals feel pressured to be perfect by others, can be destructive, leading to conflict with others, depressive symptoms, and problematic drinking. However, its impact on friendships is not well-explored. This study examined 174 emerging adult friendship dyads using a 4-wave, 4-month dyadic design. Data were analyzed using longitudinal actor-partner interdependence models. Using a novel friend-specific measure of socially prescribed perfectionism, we found that an individual's perceived expectation to be perfect from a friend was positively associated with increased conflict between friends, as well as with higher levels of depressive symptoms and problematic drinking in the individual. Findings lend credence to longstanding theoretical accounts and case histories suggesting socially prescribed perfectionism leads to harmful individual and relational outcomes and extends them to the specific context of friendships.

Recognition that schools should be responsive to children who are impacted by adversity and trauma is burgeoning internationally. However, consensus regarding the necessary components of a trauma-informed school is lacking. This research developed expert-informed and internationally relevant best-practice trauma-informed principles for schools. A four-phase methodology included (i) identification of school-relevant trauma-informed practice programs, (ii) inductive thematic analysis of the main concepts underlying programs, (iii) phrasing of draft Principles and (iv) Principle revision and finalisation via a two-round Delphi survey with international experts. Excellent agreement by experts on the importance of all Principles was achieved (round 1 [greater than or equal to] 86.4%, 2 [greater than or equal to] 92.3%). The final 'International Trauma-Informed Practice Principles for Schools' (ITIPPS) include four Overarching (A-D) and 10 Practice Principles (1-10). Summarised, these include that the school: (A) is student focussed; (B) models compassion and generosity; (C) is understanding and responsive; (D) incorporates recognition of their First Nations peoples in the school's ethos: (1) prioritises safety and wellbeing; (2) models positive relationships; (3) provides a positive culture and connects; (4) consults and collaborates; (5) supports vulnerable students; (6) teaches social and emotional learning; (7) provides trauma-informed practice training; (8) is predictable yet flexible; (9) identifies and nurtures strengths and (10) reflects, changes and grows. The ITIPPS provide clear guidance for education sectors, schools and other settings about appropriate learning environments for children and young people impacted by trauma. Research is now underway in Western Australian schools to pilot test the feasibility and impact of using the ITIPPS within a framework (thoughtfulschools.org.au) to establish trauma-informed schools.

Educational outcomes from traditionally underrepresented groups are generally worse than for their more advantaged peers. This problem is typically known as the awarding gap (we use the term awarding gap over 'attainment gap' as attainment places the responsibility on students to attain at equal levels) and continues to pose a challenge for educational systems across the world. While Learning Analytics (LA) dashboards help identify patterns contributing to the awarding gap, they often lack stakeholder involvement, offering very little support to institutional Equality, Diversity and Inclusion (EDI) leads or educators to pinpoint and address these gaps. This paper introduces an innovative EDI LA dashboard, co-created with diverse stakeholders. Rigorously evaluated, the dashboard provides fine-grained insights and course-level analysis, empowering institutions to effectively address awarding gaps and contribute to a diverse and inclusive higher education landscape.

In recent decades, researchers' interest in the role of emotions in individual political learning has grown. However, it is still unclear whether and how discrete emotions are associated with political learning. Through a cross-disciplinary systematic review and multilevel meta-analysis, we reviewed which discrete emotions have been analyzed in the context of political learning so far and meta-analytically synthesized how these emotions relate to political learning. We addressed this question by synthesizing associations between discrete emotions and various aspects of learning about political matters, such as political attention, information seeking, discussions, knowledge, and knowledge gain. The final dataset included 66 publications with 486 effect sizes, involving more than 100,000 participants. Most of the effect sizes were based on negative-activating emotions (65%; mainly anxiety, 32%, and anger, 19%) and positive-activating emotions (32%; mainly enthusiasm, 15%), while studies on positive-deactivating emotions (e.g., contentment) and negative-deactivating emotions (e.g., sadness) are largely lacking. We uncovered small positive associations (r = 0.05 to 0.13) for activating emotions, of both negative (especially anger) and positive valence (e.g., enthusiasm, only in cross-sectional designs), but no associations for negative-deactivating emotions. We discuss theoretical implications and recommend future research to include previously unconsidered emotions in order to extend existing findings.

Both achievement goals and achievement emotions have empirically been found to be important within educational contexts. This meta-analysis examined the interrelations among six achievement goals and fifteen achievement emotions and various moderators by analyzing 2,644 effect sizes from 355 studies with 155,208 participants. The findings revealed interrelations among achievement goals and achievement emotions that mainly corroborate theoretical assumptions. Mastery and performance goals showed associations with activity and outcome emotions. The results for work-avoidance goals confirmed the assumption that engaging in work avoidance is particularly related to negative activity emotions. Relational goals are positively linked to positive affect and enjoyment. Facets of mastery goals were identified as relevant moderators of the interrelations among achievement goals and emotions, in contrast to population. The results highlight the relevance of considering the interplay among achievement goals and achievement emotions at a specific level, as opposed to considering only the affective level, as well as differentiating between activity and outcome emotions to better understand their relationships with achievement goals.

Young people growing up in England from a poorer background are less likely to progress into higher education compared to their better off counterparts. This is especially true with respect to more selective universities. This study used government administrative data to gauge the effectiveness of the 'Realising Opportunities' programme, which provides a package of support to prospective university applicants from disadvantaged backgrounds to facilitate their progression to more selective universities. Data was gathered concerning 769 16 to 18-year-old students who took part in the programme--which is delivered by a consortium of selective universities--between 2015 and 2017. This data revealed participants' personal characteristics (e.g., gender, ethnicity and socioeconomic status), school attainment and eventual university destination (or lack thereof). Additionally, national administrative data was sourced from the Department for Education's National Pupil Database and the Higher Education Statistics Agency for the entire cohort of state school pupils in England who turned 16 in the 2014-2015 academic year. This national data was used to generate a statistical model that could predict the likelihood of a young person in England progressing to a selective university based on their school attainment and other personal characteristics. Data concerning the programme participants was fed through the model and it was observed that the number of participants who had in fact progressed to selective universities greatly exceeded that predicted. Participation in the Realising Opportunities programme therefore appeared to be positively associated with an increased likelihood of progression to a selective university.

Challenging behavior (CB) is a common occurrence in early childhood and frequently occurs in young children with disabilities. CB is also culturally perceived and includes differences in how caregivers understand and define the topography of CB. Despite the cultural interpretation, CB is known to impact the child and their family but there has been little exploration of what marginalized caregivers perceive as the impact of the CB that their young children with disabilities exhibit. We used semi-structured interviews to explore the perceptions of 24 caregivers, who identified as Black, Mexican American, and White, about the impact of their child's CB. Caregivers shared how the CB impacted themselves, their families, their child, and others. Although much of the impact was similar among caregivers, we discuss nuanced differences across ethnic groups.

The purpose of this study was to analyze and compare the linguistic content of the Spanish HINT and the Spanish AzBio sentence tests. The results revealed that the Spanish AzBio is linguistically more complex as compared with the Spanish HINT in terms of sentence length, complexity, and grammatical structure.

Background: The emergence of Generative Artificial Intelligence has brought a number of ethical and practical issues to higher education. Solid experimental evidence is yet inadequate to set the functional rules for the new technology. Objectives: The objective of this study is to analyse the experience of undergraduate students' interaction with ChatGPT and contribute to identifying the problems arising from the widespread use of artificial intelligence. Methods: Junior university students (N = 25) were assigned the task of working on their seminar essays with the aid of ChatGPT. Most students were novices with this tool (the study was conducted in the spring of 2023). Their essays were analysed qualitatively, according to the principles of the general inductive approach. Results and Conclusions: The initial attitudes towards artificial intelligence were almost equally distributed from enthusiastic to indifferent and cautious, with one student refusing to interact with the chatbot on ideological grounds. After the first experience, most of the students declared themselves adopters of the new technology. We have found some evidence for enhancing critical thinking competence when using ChatGPT, as well as examples of unquestioned reliance on its outputs. The tendency to personification of the chatbot was apparent in the students' essays. Implications: The findings show how easily the students embrace artificial intelligence and suggest a failure of any attempts for its strict regulation. This, on the other hand, underlines the need for emphasis on personal and research-oriented approaches in teaching and learning.

Background: A resurgence in teaching coding in primary school classrooms has led to a pedagogical swing towards using physical computing and coding to develop students' use of algorithms, computational thinking, and problem-solving skills. Two obstacles impede the optimal development of these objectives: the availability of a suitable pedagogy and an instructional sequencing model for primary school teachers to effectively present coding and computational thinking concepts and skills to students in alignment with their developmental stage. Objective: This study aims to address both obstacles by introducing the 3C Model, a newly developed instructional sequence grounded in established pedagogies and designed to effectively teach coding and computational thinking skills to primary school students based on their developmental stage. Methods: The qualitative study employed two data sources to triangulate findings, using: (1) semi-structured interviews and thematic analysis to investigate 11 primary school students' perceptions of their learning experiences with the 3C Model, and (2) researcher observations along with reflections of the students' developed and demonstrated learning through the method of knowing-in-action, reflection-in-action, and reflection-on-action. Results and Conclusions: The findings of this study fill a gap in the existing literature by demonstrating that the pedagogical and sequential approach embedded in the 3C Model not only enhanced students' engagement levels but also resulted in improved curriculum learning outcomes. The 3C Model provides teachers with a coherent and age-appropriate instructional structure. It uses physical computing devices and digital coding platforms to introduce coding concepts, furthering the development of computational thinking skills in primary school students beyond mere procedural and rote learning. Implications: The study holds important implications for practical applications, as it addresses an absence in the literature of an established pedagogy and instructional sequencing model for effectively teaching coding and computational thinking concepts and skills to primary school students. Drawing on established pedagogical and developmental learning theories, the 3C Model provides primary school teachers with an engaging, age-appropriate instructional method that avoids decontextualised teaching and surface-based learning. Instead, it encourages collaborative student work and contextualised learning, steering away from isolated and generic approaches.

Recent research syntheses have identified several potentially high-leverage teaching strategies for improving low-attaining secondary school students' learning of mathematics. These strategies include the structured use of representations and manipulatives and an emphasis on derived facts and estimation. This paper reports on 70 semi-structured interviews conducted with low-attaining students in Years 9-10 (ages 13-15) in England. The interviews addressed the students' perceptions of learning mathematics and the teaching strategies that they experienced and believed were most helpful. Many students reported rarely using number lines, not spontaneously estimating answers and being unfamiliar with derived facts. During the interviews, with minimal direction, students often showed that they were well able to make use of these strategies; however, they did not report making spontaneous use of them independently. We conclude that many of the most well-evidenced and recommended strategies to support low-attaining students in mathematics appear to be unfamiliar and unvalued, and we discuss how this might be addressed.

This quantitative survey-based study examines 366 Czech and 532 Turkish preschool teachers' compassion levels and psychological well-being. The Adult Compassion Scale and Psychological Well-being Scale were used as the data-collection tools, and Mann-Whitney U testing and Kruskal Wallis-H testing were used for data analysis. Although Turkish preschool teachers' compassion levels were found to be higher than Czech participants, the Turkish preschool teachers' psychological well-being was lower. While participants' compassion did not differ significantly across gender, parent/non-parent status, or the presence/absence of children with special needs in their classrooms, significant differences were associated with age, seniority, personal education level, marital status, age group of children taught, class size, and faith. While psychological well-being did not differ significantly across presence/absence of special-needs children, seniority, personal education level, age group of children taught, or faith, there were significant differences across gender, age, parenthood, marital status and class size. There was also a positive and moderately significant relationship between the preschool teachers' compassion and their psychological well-being.

Current research underscores that there are only a few evidence-based programs that teach STEM (science, technology, engineering, and mathematics) as part of their curriculum, especially for autistic students. Even fewer programs focus on engineering and design learning. Hence, we developed an informal afterschool maker program to develop autistic and non-autistic students' interests in engineering to understand their experiences learning STEM concepts and values while applying the engineering mindset to develop projects. This qualitative study aimed to explore and understand students' experiences participating in STEM activities in the maker club. We interviewed twenty-six students (seventeen autistic and nine non-autistic), nine teachers, and thirteen parents representing diverse cultural and socio-economic backgrounds across three public middle schools in a large urban metropolitan city between 2018 and 2019. Our thematic analysis yielded four themes: (1) "active participation in STEM"; (2) "curiosity about STEM topics, concepts, and practices"; (3) "capacity-building to engage in STEM learning"; and (4) "understanding of the importance of STEM education in daily life." The results of this study enabled us to understand that students were deeply engaged with the content and curriculum of our program, expanded their knowledge base about scientific concepts, used engineering-specific scientific terminologies, and engaged with the engineering design process to conceptualize, test, improvise, and problem-solve. Furthermore, this afterschool engineering education program created a safe, nurturing, and stimulating environment for students to build engineering readiness skills.

Since the introduction of new legislation in 2016, questions of inclusive policy have been constantly discussed not only in schools, but also among professionals, parents, and politicians. This article is part of a larger research survey mapping the state of inclusive education at all Czech Republic secondary schools. It presents the results for two regions in order to show what attitudes and views are held by principals on the implementation of inclusion in the education system. The research was carried out as a qualitative study and semi-structured interview were employed as the research method. The obtained data were analysed using the grounded theory method. The results show that inclusion is not generally accepted by school principals. There are schools that are very pro-inclusive, but there are also schools that fundamentally reject inclusion. Initial assumptions that inclusion has been best received by general secondary schools were not confirmed. On the contrary, it turns out that the type of school does not matter as much as the attitudes of the seniors' pedagogical staff towards inclusion. Their behaviour and attitudes significantly influence the whole school climate, which is passed on to all actors as well as how the school functions overall in working with pupils with special needs.

Copper played a central role in the material culture of ancient Egypt. Appearing in the archaeological record as early as the fourth millennium BCE, copper and copper alloys were the most widely used metals throughout pharaonic history. Significant copper ore deposits, such as those of the Eastern Desert and Sinai, were located in proximity to the Nile Valley and were usually mined through large state-organized expeditions. In addition to textual and iconographic evidence, copper alloy objects constitute a valuable source for our understanding of the procurement, use, and circulation of goods within ancient Egyptian society. With the advancement of scientific methods their analysis has become part of the wider development of archaeometallurgy, which aims to shed light on the entire production chain of metals in their historical and social contexts. Indeed, Egyptology, archaeology, and archaeometallurgy are complementary and can benefit from the same research questions.

Alu retrotransposons, which form the largest family of mobile DNA elements in the human genome, have recently come to attention as a potential source of regulatory novelties, most notably by participating in enhancer function. Even though Alu transcription by RNA polymerase III is subjected to tight epigenetic silencing, their expression has long been known to increase in response to various types of stress, including viral infection. Here we show that, in primary human fibroblasts, adenovirus small e1a triggered derepression of hundreds of individual Alus by promoting TFIIIB recruitment by Alu-bound TFIIIC. Epigenome profiling revealed an e1a-induced decrease of H3K27 acetylation and increase of H3K4 monomethylation at derepressed Alus, making them resemble poised enhancers. The enhancer nature of e1a-targeted Alus was confirmed by the enrichment, in their upstream regions, of the EP300/CBP acetyltransferase, EP400 chromatin remodeler and YAP1 and FOS transcription factors. The physical interaction of e1a with EP400 was critical for Alu derepression, which was abrogated upon EP400 ablation. Our data suggest that e1a targets a subset of enhancer Alus whose transcriptional activation, which requires EP400 and is mediated by the e1a-EP400 interaction, may participate in the manipulation of enhancer activity by adenoviruses.

BACKGROUND: Fragile X syndrome (FXS) and autism spectrum disorder (ASD) are neurodevelopmental conditions that often have a substantial impact on daily functioning and quality of life. FXS is the most common cause of inherited intellectual disability (ID) and the most common monogenetic cause of ASD. Previous literature has shown that electrophysiological activity measured by electroencephalogram (EEG) during resting state is perturbated in FXS and ASD. However, whether electrophysiological profiles of participants with FXS and ASD are similar remains unclear. The aim of this study was to compare EEG alterations found in these two clinical populations presenting varying degrees of cognitive and behavioral impairments. METHODS: Resting state EEG signal complexity, alpha peak frequency (APF) and power spectral density (PSD) were compared between 47 participants with FXS (aged between 5-20), 49 participants with ASD (aged between 6-17), and 52 neurotypical (NT) controls with a similar age distribution using MANCOVAs with age as covariate when appropriate. MANCOVAs controlling for age, when appropriate, and nonverbal intelligence quotient (NVIQ) score were subsequently performed to determine the impact of cognitive functioning on EEG alterations. RESULTS: Our results showed that FXS participants manifested decreased signal complexity and APF compared to ASD participants and NT controls, as well as altered power in the theta, alpha and low gamma frequency bands. ASD participants showed exaggerated beta power compared to FXS participants and NT controls, as well as enhanced low and high gamma power compared to NT controls. However, ASD participants did not manifest altered signal complexity or APF. Furthermore, when controlling for NVIQ, results of decreased complexity in higher scales and lower APF in FXS participants compared to NT controls and ASD participants were not replicated. CONCLUSIONS: These findings suggest that signal complexity and APF might reflect cognitive functioning, while altered power in the low gamma frequency band might be associated with neurodevelopmental conditions, particularly FXS and ASD.

BackgroundStandard treatment for patients with newly diagnosed glioblastoma includes surgery, radiotherapy (RT), and temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). The proteasome has long been considered a promising therapeutic target because of its role as a central biological hub in tumor cells. Marizomib is a novel pan-proteasome inhibitor that crosses the blood-brain barrier.MethodsEuropean Organisation for Research and Treatment of Cancer 1709/Canadian Cancer Trials Group CE.8 was a multicenter, randomized, controlled, open-label phase 3 superiority trial. Key eligibility criteria included newly diagnosed glioblastoma, age > 18 years and Karnofsky performance status > 70. Patients were randomized in a 1:1 ratio. The primary objective was to compare overall survival (OS) in patients receiving marizomib in addition to TMZ/RT→TMZ with patients receiving the only standard treatment in the whole population and in the subgroup of patients with MGMT promoter-unmethylated tumors.ResultsThe trial was opened at 82 institutions in Europe, Canada, and the U.S. A total of 749 patients (99.9% of the planned 750) were randomized. OS was not different between the standard and the marizomib arm (median 17 vs. 16.5 months; HR = 1.04; P = .64). PFS was not statistically different either (median 6.0 vs. 6.3 months; HR = 0.97; P = .67). In patients with MGMT promoter-unmethylated tumors, OS was also not different between standard therapy and marizomib (median 14.5 vs. 15.1 months, HR = 1.13; P = .27). More CTCAE grade 3/4 treatment-emergent adverse events were observed in the marizomib arm than in the standard arm.ConclusionsAdding marizomib to standard temozolomide-based radiochemotherapy resulted in more toxicity, but did not improve OS or PFS in patients with newly diagnosed glioblastoma.

The successful use of molecular dyes for solar energy conversion requires efficient charge injection, which in turn requires the formation of states with sufficiently long lifetimes (e.g., triplets). The molecular structure elements that confer this property can be found empirically, however computational predictions using ab initio electronic structure methods are invaluable to identify structure-property relations for dye sensitizers. The primary challenge for simulations to elucidate the electronic and nuclear origins of these properties is a spin-orbit interaction which drives transitions between electronic states. In this work, we present a computational analysis of the spin-orbit corrected linear absorption cross sections and intersystem crossing rate coefficients for a derivative set of phosphonated tris(2,2'-bipyridine)ruthenium(2+) dye molecules. After sampling the ground state vibrational distributions, the predicted linear absorption cross sections indicate that the mixture between singlet and triplet states plays a crucial role in defining the line shape of the metal-to-ligand charge transfer bands in these derivatives. Additionally, an analysis of the intersystem crossing rate coefficients suggests that transitions from the singlet into the triplet manifolds are ultrafast with rate coefficients on the order of 1013 s-1 for each dye molecule.

BACKGROUND: Chronic lung disease of prematurity, called bronchopulmonary dysplasia (BPD), lacks effective therapies, stressing the need for preclinical testing systems that reflect human pathology for identifying causal pathways and testing novel compounds. Alveolar organoids derived from human pluripotent stem cells (hPSC) are promising test platforms for studying distal airway diseases like BPD, but current protocols do not accurately replicate the distal niche environment of the native lung. Herein, we investigated the contributions of cellular constituents of the alveolus and fetal respiratory movements on hPSC-derived alveolar organoid formation. METHODS: Human PSCs were differentiated in 2D culture into lung progenitor cells (LPC) which were then further differentiated into alveolar organoids before and after removal of co-developing mesodermal cells. LPCs were also differentiated in Transwell® co-cultures with and without human fetal lung fibroblast. Forming organoids were subjected to phasic mechanical strain using a Flexcell® system. Differentiation within organoids and Transwell® cultures was assessed by flow cytometry, immunofluorescence, and qPCR for lung epithelial and alveolar markers of differentiation including GATA binding protein 6 (GATA 6), E-cadherin (CDH1), NK2 Homeobox 1 (NKX2-1), HT2-280, surfactant proteins B (SFTPB) and C (SFTPC). RESULTS: We observed that co-developing mesenchymal progenitors promote alveolar epithelial type 2 cell (AEC2) differentiation within hPSC-derived lung organoids. This mesenchymal effect on AEC2 differentiation was corroborated by co-culturing hPSC-NKX2-1+ lung progenitors with human embryonic lung fibroblasts. The stimulatory effect did not require direct contact between fibroblasts and NKX2-1+ lung progenitors. Additionally, we demonstrate that episodic mechanical deformation of hPSC-derived lung organoids, mimicking in situ fetal respiratory movements, increased AEC2 differentiation without affecting proximal epithelial differentiation. CONCLUSION: Our data suggest that biophysical and mesenchymal components promote AEC2 differentiation within hPSC-derived distal organoids in vitro.

Abstract: As a promising candidate for nonvolatile memory devices, the hafnia‐based ferroelectric system has recently been a hot research topic. Although significant progress has been made over the past decade, the endurance problem is still an obstacle to its final application. In perovskite‐based ferroelectrics, such as the well‐studied Pb[ZrxTi1−x]O3 (PZT) family, polarization fatigue has been discussed within the framework of the interaction of charged defects (such as oxygen vacancies) with the moving domains during the switching process, particularly at the electrode‐ferroelectric interface. Armed with this background, a hypothesis is set out to test that a similar mechanism can be in play with the hafnia‐based ferroelectrics. The conducting perovskite La‐Sr‐Mn‐O is used as the contact electrode to create La0.67Sr0.33MnO3 / Hf0.5Zr0.5O2 (HZO)/ La0.67Sr0.33MnO3 capacitor structures deposited on SrTiO3‐Si substrates. Nanoscale X‐ray diffraction is performed on single capacitors, and a structural phase transition from polar o‐phase toward non‐polar m‐phase is demonstrated during the bipolar switching process. The energy landscape of multiphase HZO has been calculated at varying oxygen vacancy concentrations. Based on both theoretical and experimental results, it is found that a polar to non‐polar phase transformation caused by oxygen vacancy redistribution during electric cycling is a likely explanation for fatigue in HZO.

BACKGROUND: The amygdala is highly implicated in an array of psychiatric disorders but is not accessible using currently available noninvasive neuromodulatory techniques. Low-intensity transcranial focused ultrasound (TFUS) is a neuromodulatory technique that has the capability of reaching subcortical regions noninvasively. METHODS: We studied healthy older adult participants (N = 21, ages 48-79 years) who received TFUS targeting the right amygdala and left entorhinal cortex (active control region) using a 2-visit within-participant crossover design. Before and after TFUS, behavioral measures were collected via the State-Trait Anxiety Inventory and an emotional reactivity and regulation task utilizing neutral and negatively valenced images from the International Affective Picture System. Heart rate and self-reported emotional valence and arousal were measured during the emotional reactivity and regulation task to investigate subjective and physiological responses to the task. RESULTS: Significant increases in both self-reported arousal in response to negative images and heart rate during emotional reactivity and regulation task intertrial intervals were observed when TFUS targeted the amygdala; these changes were not evident when the entorhinal cortex was targeted. No significant changes were found for state anxiety, self-reported valence to the negative images, cardiac response to the negative images, or emotion regulation. CONCLUSIONS: The results of this study provide preliminary evidence that a single session of TFUS targeting the amygdala may alter psychophysiological and subjective emotional responses, indicating some potential for future neuropsychiatric applications. However, more work on TFUS parameters and targeting optimization is necessary to determine how to elicit changes in a more clinically advantageous way.

To understand the roles of acute-phase viral dynamics and host immune responses in post-acute sequelae of SARS-CoV-2 infection (PASC), we enrolled 136 participants within 5 days of their first positive SARS-CoV-2 real-time PCR test. Participants self-collected up to 21 nasal specimens within the first 28 days post-symptom onset; interviewer-administered questionnaires and blood samples were collected at enrollment, days 9, 14, 21, 28, and month 4 and 8 post-symptom onset. Defining PASC as the presence of any COVID-associated symptom at their 4-month visit, we compared viral markers (quantity and duration of nasal viral RNA load, infectious viral load, and plasma N-antigen level) and host immune markers (IL-6, IL-10, TNF-α, IFN-α, IFN-γ, MCP, IP-10, and Spike IgG) over the acute period. Compared to those who fully recovered, those reporting PASC demonstrated significantly higher maximum levels of SARS-CoV-2 RNA and N-antigen, burden of RNA and infectious viral shedding, and lower Spike-specific IgG levels within 9 days post-illness onset. No significant differences were identified among a panel of host immune markers. Our results suggest early viral dynamics and the associated host immune responses play a role in the pathogenesis of PASC, highlighting the importance of understanding early biological markers in the natural history of PASC.

Botryosphaeriaceae species are the major causal agents of walnut dieback worldwide, along with Diaporthe species. Botryosphaeria dothidea and Neofusicoccum parvum are the only two Botryosphaeriaceae species associated with this recently emergent disease in France, and little is known about their diversity, structure, origin and dispersion in French walnut orchards. A total of 381 isolates of both species were genetically typed using a sequence-based microsatellite genotyping (SSR-seq) method. This analysis revealed a low genetic diversity and a high clonality of these populations, in agreement with their clonal mode of reproduction. The genetic similarity among populations, regardless of the tissue type and the presence of symptoms, supports the hypothesis that these pathogens can move between fruits and twigs and display latent pathogen lifestyles. Contrasting genetic patterns between N. parvum populations from Californian and Spanish walnut orchards and the French ones suggested no conclusive evidence for pathogen transmission from infected materials. The high genetic similarity with French vineyards populations suggested instead putative transmission between these hosts, which was also observed with B. dothidea populations. Overall, this study provides critical insight into the epidemiology of two important pathogens involved in the emerging dieback of French walnut orchards, including their distribution, potential to mate, putative origin and disease pathways.

Introduction: Historically, prehospital care of trauma patients has included nearly universal use of a cervical collar (C-collar) and long spine board (LSB). Due to recent evidence demonstrating harm in using LSBs, implementation of new spinal motion restriction (SMR) protocols in the prehospital setting should reduce LSB use, even among patients with spinal cord injury. Our goal in this study was to evaluate the rates of and reasons for LSB use in high-risk patients—those with hospital-diagnosed spinal cord injury (SCI)—after statewide implementation of SMR protocols.Methods: Applying data from a state emergency medical services (EMS) registry to a state hospital discharge database, we identified cases in which a participating EMS agency provided care for a patient later diagnosed in the hospital with a SCI. Cases were then retrospectively reviewed to determine the prevalence of both LSB and C-collar use before and after agency adoption of a SMR protocol. We reviewed cases with LSB use after SMR protocol implementation to determine the motivations driving continued LSB use. We used simple descriptive statistics, odds ratios (OR) with 95% confidence intervals (CI) to describe the results.Results: We identified 52 EMS agencies in the state of Arizona with 417,979 encounters. There were 225 patients with SCI, of whom 74 were excluded. The LSBs were used in 52 pre-SMR (81%) and 49 post-SMR (56%) cases. The odds of LSB use after SMR protocol implementation was 70% lower than it had been before implementation (OR 0.297, 95% CI 0.139–0.643; P = 0.002). Use of a C-collar after SMR implementation was not significantly changed (OR 0.51, 95% CI 0.23–1.143; P = 0.10). In the 49 cases of LSB use after agency SMR implementation, the most common reasons for LSB placement were ease of lifting (63%), placement by non-transporting agency (18%), and extrication (16.3%). High suspicion of SCI was determined as the primary or secondary reason for not removing LSB after assessment in 63% of those with LSB placement, followed by multiple transfers required (20%), and critical illness (10%).Conclusion: Implementation of selective spinal motion restriction protocols was associated with a statistically significant decrease in the utilization of long spine boards among prehospital patients with acute traumatic spinal cord injury.

TBI-223, a novel oxazolidinone for tuberculosis, is designed to provide improved efficacy and safety compared to linezolid in combination with bedaquiline and pretomanid (BPaL). We aim to optimize the dosing of TBI-223 within the BPaL regimen for enhanced therapeutic outcomes. TBI-223 is investigated in preclinical monotherapy, multidrug therapy, and lesion penetration experiments to describe its efficacy and safety versus linezolid. A translational platform incorporating linezolid and BPaL data from preclinical experiments and 4 clinical trials (NCT00396084, NCT02333799, NCT03086486, NCT00816426) is developed, enabling validation of the framework. TBI-223 preclinical and Phase 1 data (NCT03758612) are applied to the translational framework to predict clinical outcomes and optimize TBI-223 dosing in combination with bedaquiline and pretomanid. Results indicate that daily doses of 1200-2400 mg TBI-223 may achieve efficacy comparable to the BPaL regimen, with >90% of patients predicted to reach culture conversion by two months.