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Summary: TSPEAR variants cause autosomal recessive ectodermal dysplasia (ARED) 14. The function of TSPEAR is unknown. The clinical features, the mutation spectrum, and the underlying mechanisms of ARED14 are poorly understood. Combining data from new and previously published individuals established that ARED14 is primarily characterized by dental anomalies such as conical tooth cusps and hypodontia, like those seen in individuals with WNT10A-related odontoonychodermal dysplasia. AlphaFold-predicted structure-based analysis showed that most of the pathogenic TSPEAR missense variants likely destabilize the β-propeller of the protein. Analysis of 100000 Genomes Project (100KGP) data revealed multiple founder TSPEAR variants across different populations. Mutational and recombination clock analyses demonstrated that non-Finnish European founder variants likely originated around the end of the last ice age, a period of major climatic transition. Analysis of gnomAD data showed that the non-Finnish European population TSPEAR gene-carrier rate is ∼1/140, making it one of the commonest AREDs. Phylogenetic and AlphaFold structural analyses showed that TSPEAR is an ortholog of drosophila Closca, an extracellular matrix-dependent signaling regulator. We, therefore, hypothesized that TSPEAR could have a role in enamel knot, a structure that coordinates patterning of developing tooth cusps. Analysis of mouse single-cell RNA sequencing (scRNA-seq) data revealed highly restricted expression of Tspear in clusters representing enamel knots. A tspeara−/−;tspearb−/− double-knockout zebrafish model recapitulated the clinical features of ARED14 and fin regeneration abnormalities of wnt10a knockout fish, thus suggesting interaction between tspear and wnt10a. In summary, we provide insights into the role of TSPEAR in ectodermal development and the evolutionary history, epidemiology, mechanisms, and consequences of its loss of function variants.

Most U.S. metropolitan areas developed alongside the automobile, producing neighborhoods of relatively low density. Consequently, access to opportunities in these neighborhoods is predicated on having an automobile, yet many households do not have the resources to purchase one outright, relying on automobile loans to spread out the purchase price. While automobile loans can enable automobile ownership, they also significantly increase the vehicle purchase price, particularly for non-white consumers subject to discriminatory lending practices.In this study, we rely on data from the University of California Consumer Credit Panel from Experian to examine the determinants and geography of automobile debt and its consequences in California, testing whether various automobile debt measures disproportionately affect non-white neighborhoods.We find that, controlling for other factors associated with automobile lending including income, Black and Latino/a neighborhoods have higher total automobile debt, debt burdens (debt relative to income), and automobile loan delinquency rates. In particular, Latino/a neighborhoods shoulder significant automobile debt, while borrowers in Black neighborhoods have the highest delinquency rates. Factors associated with lower total automobile debt and automobile debt burden include better credit ratings, higher residential densities, urban locations, and proximity to rail stations.The findings underscore the importance of policies to offset the costs of automobile ownership and access. As part of this, policymakers should adopt and enforce fair lending rules to combat discriminatory and predatory practices and facilitate access to high-quality financial institutions and products in communities of color.

COVID-19 altered travel patterns in the U.S. Studies have analyzed the effect of the pandemic on travel mode, including working from home, but few have focused on automobile ownership—a relationship with potentially long-term consequences for accessibility, household budgets and debt, and policy efforts to meet climate goals.To understand the association between the pandemic and automobile ownership, we rely on a unique credit panel dataset from Experian and examine three different automobile loan-related outcome measures: annualized growth rate of new automobile loan balances, average new loan size, and the number of new loans. We focus specifically on changes across loans in neighborhoods by race/ethnicity, hypothesizing larger increases in automobile debt in Black and Latino/a neighborhoods, where workers are less likely to be able to telework. The annualized growth rate of new automobile loans increased during the pandemic across all neighborhoods by race/ethnicity, increasing most rapidly in Latino/a neighborhoods. Controlling for other factors, loan size increased similarly across neighborhoods by race/ethnicity. The increase in automobile lending in Latino/a neighborhoods, therefore, likely was explained by a significant uptick in the number of new loans.The growth in automobile lending during the pandemic was potentially prompted by pandemic-induced changes in the need for automobiles and facilitated by an expanded social safety net. As the pandemic and its various forms of public financial assistance recede, the findings underscore the importance of ongoing assistance in enabling automobile ownership or shared access among households with limited means whose livelihoods depend on the access that vehicles provide.

Daily vehicle travel collapsed with the onset of the COVID-19 pandemic in early 2020 but largely bounced back by late 2021. The pandemic caused dramatic changes to working, schooling, shopping, and leisure activities, and to the travel associated with them. Several of these changes have so far proven enduring. So, while overall vehicle travel had largely returned to pre-pandemic levels by late 2021, the underlying drivers of this travel have likely changed.To examine one element of this issue, we analyzed whether patterns of daily trip-making shifted temporally between the fall of 2019 and 2021 in the Greater Los Angeles megaregion. We used location-based service data to examine vehicle trip originations for each hour of the day at the U.S. census block group level in October 2019 and October 2021. We observed notable shifts in the timing of post-pandemic PM peak travel, so we examined changes in the ratio of mid-week trips originating in the early afternoon (12–3:59 PM) and the late afternoon/early evening (4–7:59 PM).We found a clear shift in the temporal distribution of PM trip-making, with relatively more late PM peak period trip-making prior to the pandemic, and more early PM peak trip-making in 2021. The peak afternoon/evening trip-making hour shifted from 5–5:59 PM to 3–3:59 PM. We also found that afternoon/evening trip-making in each year is largely explained by three workplace-area/school-area factors: (1) the number of schoolchildren in a block group (earlier); (2) block groups with large shares of potential remote workers (earlier), and (3) block groups with large shares of low-wage jobs and workers of color (later, except for Black workers in 2021). We found the earlier shift in PM peak travel between pre- and late-pandemic periods to be explained most by (1) higher shares of potential remote workers and (2) higher shares of low-wage jobs and workers of color. These findings suggest that the rise of working from home has likely led to a shift in PM peak travel earlier in the afternoon when school chauffeuring trips are most common. This is especially true for low-income workers and workers of color.

This study reviews factors affecting Muslim consumer behavior towards halal food products, using bibliometric analysis to identify key research trends and influential works in the field. A bibliometric analysis was conducted on 613 peer-reviewed articles from the Scopus database (2015-2024), using VOSviewer to visualize co-citation, keyword clusters, and research themes. The analysis reveals that religious beliefs, halal certification trust, and perceived product quality are key drivers of halal food purchasing behavior. Interest in halal products is growing globally, appealing to both Muslim and non-Muslim consumers due to perceived ethical and safety standards. The study identifies top contributors, influential journals, and leading countries in halal food research. Insights suggest further exploration into halal certification for alternative proteins, sustainability, and comparative studies across diverse regions. The findings are useful for researchers and businesses targeting the global halal market. This study provides a comprehensive bibliometric review of halal consumer behavior, highlighting trends and research gaps. It is essential for those seeking to understand the evolving dynamics of the halal food sector. Keywords: Halal Food, Consumer Behavior, Halal Certification, Bibliometric Analysis, VOSviewer

Abstract The pharmaceutical industry has been primarily focused on developing synthetic drugs to address orofacial pain (OFP)-related conditions. There is limited knowledge regarding the efficacy of the use of herbal extracts in treating OFP. A systematic review and a meta-analysis of 62 randomized controlled trials assessing the analgesic effects of herbal extracts on pain intensity in various orofacial conditions was conducted. The intervention comprised the use of herbal extracts compared with a placebo and/or standard treatment. The primary outcome was pain intensity assessed before and after the intervention. The pain scores were compared with the baseline scores in each treatment. When compared with standard therapy, the pooled results of the patients who received herbal extracts revealed lower pain intensity in periodontal pain (MD = -0.92[-6.69, 4.85]), oral surgery pain (MD = 18.80[8.80, 28.79]), oral neuropathic pain (MD = 20.34[6.16, 34.52]), endodontic pain (MD = -8.04[-11.72, -4.37]), oral mucosal pain (MD = 8.74[2.76, 14.73]), and temporomandibular pain (MD = 30.94[6.04, 55.83]). The findings indicated a pain-attenuating effect of herbal extracts such as cannabis, turmeric, capsaicin, licorice, ginger, chamomile, clove, Hypericum perforatum, and Arnica montana. These findings revindicate that herbal extracts may be valuable alternatives to traditional pain medications and promising source for the development of new active ingredients for pharmaceuticals.

Abstract Background and objective Tricuspid valve replacement (TVR) is required when repair is not feasible, and it continues to be a relatively high-risk procedure owing to the complex medical and/or surgical profile of patients. The choice between mechanical and biological prostheses for TVR remains a subject of debate owing to their distinct advantages and disadvantages. This study aimed to analyse and compare the clinical outcomes of these two types of prostheses in the tricuspid position. Methods PubMed, EMBASE, Web of Science, and the COCHRANE library were searched from 1995 to April 2023 for studies comparing clinical outcomes of mechanical versus biological valves in the tricuspid position. Data on 30-day mortality, reoperations, 5-year valve failure rates, thrombotic/thromboembolic events, and long-term survival were extracted, pooled, and analysed. Forest plots were generated using a random-effects model. Results From an initial pool of 4716 citations, 37 studies meeting our inclusion criteria were assessed, collectively encompassing 8316 prostheses (3796 mechanical, 4520 bioprostheses). Our analysis revealed that mechanical valves exhibited a non-significant trend towards diminished 30-day mortality (RR = 0.85, 95% CI = 0.69–1.06). A distinct disparity emerged in valve durability, with mechanical valves demonstrating a significantly increased risk of 5-year valve failure (RR = 2.21, 95% CI = 1.38–3.56). Strikingly, mechanical valves displayed a substantial six-fold elevated risk of thrombotic events (RR = 6.29, 95% CI = 3.98–9.92). In contrast, the long-term survival and reoperation rates demonstrated no statistically significant differences between the two valve types. Conclusions This systematic review and meta-analysis provides insights into the selection of mechanical and bioprosthetic valves for TVR. These findings highlight the potential advantages and disadvantages of mechanical and bioprosthetic valves in terms of early mortality, valve durability, and thrombotic risk. Our analysis provides clinicians with evidence-based guidance for optimizing outcomes in TVR, offering a foundation for informed decision-making in this intricate surgical landscape. Despite these insights, clinicians must overcome the limitations of retrospective studies, evolving healthcare, and anticoagulant disparities to ensure careful consideration in tricuspid valve replacement decisions.

This study explores ICT profiles of teacher educators to understand personal, pedagogical and organisational factors affecting technology use in teacher education. After delineating latent profiles based on survey data, 12 teacher educators were interviewed on technology integration in educational settings for a deeper insight. Based on the Synthesis of Qualitative Research model developed to outline strategies for preparing preservice teachers to integrate technology, findings revealed key issues including teacher educators' classroom stance as role models for effective technology use, importance of technological-pedagogical content knowledge in designing technology-enriched learning environments, peer collaboration and avoidance of using technology regardless of pedagogical concerns. Issues related to assessment, professional development, attitudes and ICT competency were raised. Findings are discussed considering potential consequences for current practices and areas of future research.

The digitalisation of education has been emphasised over the last two decades, affecting and developing both the theories and practices of teaching and learning. Considering these developments, the need for addressing teachers' and students' digital competence has gained ground. In the last few years, the concept of digital agency has been noted in empirical and theoretical research - broadly focusing on the integration of information and communication technologies (ICT) in education. Nonetheless, how digital agency is understood and how it relates to the more established concept of digital competence remains unclear. To address this gap, we conducted a conceptual systematic review and examined the current state of the knowledge on digital agency. Specifically, we review the conceptualisations of digital agency, its underlying theoretical frameworks, and how it relates to digital competence and similar concepts. Database searches resulted in 32 publications, with the majority published in education and design journals and stemming from Scandinavian countries. Our findings show that out of 32 studies, only one aimed at defining digital agency explicitly. Nevertheless, for the last three years, digital agency has been more frequently used in the body of literature, emphasising the design and transformation of teaching and learning with technology towards a 'new normal' considering the post-pandemic era and lessons learned. Reviewing the extant body of knowledge on digital agency, we review the strengths and weaknesses of the concept and compare it to the more established notion of digital competence. Finally, we discuss implications for policy, research, and practice in education.

Meta-analyses and international large-scale assessments (ILSA) are key sources for informing educational policy, research, and practice. While many critical research questions could be addressed by drawing evidence from both of these sources, meta-analysts seldom integrate ILSAs, and current integration practices lack methodological guidance. The aim of this methodological review is therefore to synthesize and illustrate the principles and practices of including ILSA data in meta-analyses. Specifically, we (a) review four ILSA data inclusion approaches (analytic steps, potential, challenges); (b) examine whether and how existing meta-analyses included ILSA data; and (c) provide a hands-on illustrative example of how to implement the four approaches. Seeing the need for meta-analyses on educational inequalities, we situated the review and illustration in the context of gender differences and socioeconomic gaps in student achievement. Ultimately, we outline the steps meta-analysts could take to utilize the potential and address the challenges of ILSA data for meta-analyses in education.