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Computed tomography (CT) scanners are essential for modern imaging but require around 600 projections from various angles. We present x-ray-induced acoustic computed tomography (XACT), a method that uses radiation-induced acoustic waves for three-dimensional (3D) x-ray imaging. These spherical acoustic waves travel through tissue at 1.5 × 103 meters per second, much slower than x-rays, allowing ultrasound detectors to capture them and generate 3D images without mechanical scanning. We validate this theory by performing 3D numerical reconstructions of a human breast from a single x-ray projection and experimentally determining 3D structures of objects at different depths. Achieving resolutions of 0.4 millimeters in the XZ plane and 3.5 millimeters in the XY plane at a depth of 16 millimeters, XACT demonstrates the ability to produce 3D images from one x-ray projection, reducing radiation exposure and enabling gantry-free imaging. XACT shows great promise for biomedical and nondestructive testing applications, potentially replacing conventional CT.

In this exploratory descriptive study, changes in one cohort's responses to an authentic statistical investigation at the commencement of years 3 and 4 were analysed. Forty-four students made predictions by interpreting a data table of historical monthly temperatures, represented these data and explained their reasoning. An Awareness of Mathematical Pattern and Structure (AMPS) framework was extended to analyse students' responses at five increasing levels of predictive reasoning. More developed predictive reasoning was observed in year 4 than for year 3, as well as large individual differences in both years. Most year 4 students (87%) made predictions within the historical range, relative to half the same cohort in year 3 (54%). More year 4 students (79%) made predictions based on extraction, clustering and aggregation of these data than those in year 3 (51%). Year 4 students noticed patterns such as seasonal trends and variability in these data and observed measures of central tendency. By year 4, 57% of students' representations demonstrated transnumeration using extracted data from the table, including pictorial, column and line graphs. However, most students' representations and explanations of these data lagged behind their predictions at both year levels.

Abstract Background Educational innovation in health professional education is needed to keep up with rapidly changing healthcare systems and societal needs. This study evaluates the implementation of PACE, an innovative curriculum designed by the physiotherapy department of the HAN University of Applied Sciences in The Netherlands. The PACE concept features an integrated approach to learning and assessment based on pre-set learning outcomes, personalized learning goals, flexible learning routes, and programmatic assessment. PACE distinguishes itself from traditional education because of the flexible learning routes, vertical organization in learning communities, absence of pre-defined learning activities and class schedules, and a culture of continuous learning and development. PACE is based on three guiding principles: 1) flexible and varied, 2) self-directed and collaborative, 3) future-oriented. PACE was implemented in 2021 for first-year students. This study evaluates the implementation to inform future curriculum development. Methods A sequential explanatory mixed methods design was used to evaluate the implementation of PACE using a questionnaire, focus groups, in-depth interviews, and a national progress test allowing for benchmarking results. Participants were undergraduate physiotherapy students of cohort 2021–2022, the first group who experienced PACE and teachers involved with this cohort. Questionnaire data were analyzed using descriptive statistics. To compare mean total scores of the national progress test between four different universities a one-way ANOVA was conducted including a post-hoc analysis. Reflexive thematic analysis guidelines were applied to analyze the interview data. Results In total 82 first year students (44,6%) of cohort 2021–2022 and 36 teachers (60%) completed the questionnaire. Results show that the guiding principles were implemented as intended. Results of the national progress test on knowledge and clinical reasoning showed that students of the HAN University performed well compared to other universities. Thematic analysis of interviews and focus groups resulted in three themes and nine subthemes: 1) navigating a personalized curriculum, 2) caring and sharing, and 3) shaping professional identity. PACE contributed positively to students' intrinsic motivation, learning joy, identity development, and life-long learning skills. Areas for improvement were self-directed learning support, and teaching strategies to prompt deep learning. Conclusion The evaluation showed that the guiding principles of PACE were implemented as intended and that the innovation positively contributed to student learning,

Abstract Background Metabolism is error prone. For instance, the reduced forms of the central metabolic cofactors nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), can be converted into redox-inactive products, NADHX and NADPHX, through enzymatically catalyzed or spontaneous hydration. The metabolite repair enzymes NAXD and NAXE convert these damaged compounds back to the functional NAD(P)H cofactors. Pathogenic loss-of-function variants in NAXE and NAXD lead to development of the neurometabolic disorders progressive, early-onset encephalopathy with brain edema and/or leukoencephalopathy (PEBEL)1 and PEBEL2, respectively. Methods To gain insights into the molecular disease mechanisms, we investigated the metabolic impact of NAXD deficiency in human cell models. Control and NAXD-deficient cells were cultivated under different conditions, followed by cell viability and mitochondrial function assays as well as metabolomic analyses without or with stable isotope labeling. Enzymatic assays with purified recombinant proteins were performed to confirm molecular mechanisms suggested by the cell culture experiments. Results HAP1 NAXD knockout (NAXDko) cells showed growth impairment specifically in a basal medium containing galactose instead of glucose. Surprisingly, the galactose-grown NAXDko cells displayed only subtle signs of mitochondrial impairment, whereas metabolomic analyses revealed a strong inhibition of the cytosolic, de novo serine synthesis pathway in those cells as well as in NAXD patient-derived fibroblasts. We identified inhibition of 3-phosphoglycerate dehydrogenase as the root cause for this metabolic perturbation. The NAD precursor nicotinamide riboside (NR) and inosine exerted beneficial effects on HAP1 cell viability under galactose stress, with more pronounced effects in NAXDko cells. Metabolomic profiling in supplemented cells indicated that NR and inosine act via different mechanisms that at least partially involve the serine synthesis pathway. Conclusions Taken together, our study identifies a metabolic vulnerability in NAXD-deficient cells that can be targeted by small molecules such as NR or inosine, opening perspectives in the search for mechanism-based therapeutic interventions in PEBEL disorders. Graphical Abstract

Radiation-induced acoustics (RIA) shows promise in advancing radiological imaging and radiotherapy dosimetry methods. However, RIA signals often require extensive averaging to achieve reasonable signal-to-noise ratios, which increases patient radiation exposure and limits real-time applications. Therefore, this paper proposes a discrete wavelet transform (DWT) based filtering approach to denoise the RIA signals and avoid extensive averaging. The algorithm was benchmarked against low-pass filters and tested on various types of RIA sources, including low-energy X-rays, high-energy X-rays, and protons. The proposed method significantly reduced the required averages (1000 times less averaging for low-energy X-ray RIA, 32 times less averaging for high-energy X-ray RIA, and 4 times less averaging for proton RIA) and demonstrated robustness in filtering signals from different sources of radiation. The coif5 wavelet in conjunction with the sqtwolog threshold selection algorithm yielded the best results. The proposed DWT filtering method enables high-quality, automated, and robust filtering of RIA signals, with a performance similar to low-pass filtering, aiding in the clinical translation of radiation-based acoustic imaging for radiology and radiation oncology.

Children born to parents with fewer years of education are more likely to have depression, anxiety, and attention-deficit hyperactivity disorder (ADHD), but it is unclear to what extent these associations are causal. We estimated the effect of parents' educational attainment on children's depressive, anxiety, and ADHD traits at age 8 years, in a sample of 40,879 Norwegian children born in 1998-2009 and their parents. We used within-family Mendelian randomization, which employs genetic variants as instrumental variables, and controlled for direct genetic effects by adjusting for children's polygenic indexes. We found little evidence that mothers' or fathers' educational attainment independently affected children's depressive, anxiety, or ADHD traits. However, children's own polygenic scores for educational attainment were independently and negatively associated with these traits. Results suggest that differences in these traits according to parents' education may reflect direct genetic effects more than genetic nurture. Consequences of social disadvantage for children's mental health may however be more visible in samples with more socioeconomic variation, or contexts with larger socioeconomic disparities than present-day Norway. Further research is required in populations with more educational and economic inequality and in other age groups.

A rare neurodevelopmental disorder has been linked to a well-conserved splice site variant in the TRAPPC4 gene (c.454 + 3A > G), which causes mis-splicing of TRAPPC4 transcripts and reduced levels of TRAPPC4 protein. Patients present with severe progressive neurological symptoms including seizures, microcephaly, intellectual disability and facial dysmorphism. We have generated stem cells from fibroblasts of two individuals with the same homozygous TRAPPC4 c.454 + 3A > G pathogenic variant and used CRISPR/Cas9 editing to generate heterozygous gene-corrected isogenic controls. Clones were tested for pluripotency, differentiation potential, genotyped and karyotyped. These iPSC-based models will be used to understand disease mechanisms of TRAPPC4 disorder.

Background Personalised outcomes forecasts (POFs) were introduced among physical and exercise therapists in the Netherlands to optimise supervised exercise therapy for patients with intermittent claudication. Yet, therapists’ initial adoption and sustainable implementation of POFs can be influenced by various factors.Objectives The purpose of this study was to examine therapists’ adoption of the POFs, their fidelity to the measurement protocol for supervised exercise therapy, and their perceived barriers and facilitators for using POFs in practice.Methods A multimethod process evaluation was conducted, including quantitative descriptive and pre–post approaches, as well as a qualitative framework approach. To examine adoption, we evaluated the proportion of therapists who expressed interest in POFs by completing one of three provided e-learnings and the proportion of therapists who started using POFs in practice. To examine fidelity to the measurement protocol, we compared the per-episode proportion of follow-up measurements documented by therapists preimplementation and postimplementation. Qualitative data on barriers and facilitators were identified through semistructured interviews with therapists.Results One year after the implementation, 89% of therapists eligible to use POFs (n=1727) completed at least one e-learning and 51% of therapists started using POFs. The per-episode proportion of documented follow-up measurements per therapist increased, from a mean rate of 37% (3 months) and 22% (6 months) during the preimplementation period to a mean rate of 53% (3 months) and 32% (6 months) during the postimplementation period (p

The COVID-19 pandemic has caused significant upheaval in schools in Australia and internationally. The aim of this study was to map Australian teachers' positive and negative experiences during remote and online learning. Our study took place during the first COVID-19 wave, in the early stages of lockdown. Using an online instrument, we asked 210 primary and secondary teachers about changes in their teaching roles due to COVID-19. Responses were coded for positive and negative themes using inductive thematic analysis. The majority of teachers reported negative themes (88.6%), while half also reported positive themes (44.8%). Participants reported missing their students and struggling with excessive workload demands. They also experienced difficulties tracking student progress and felt worried for student wellbeing. Interestingly, concerns about technology were less common. Indeed, 19.1% enjoyed learning new online skills and integrating IT in new ways. Implications for student-teacher relationships, mental health, and future teaching are discussed.

Background: Seafood allergy (SA), including allergy to shellfish (crustacean and mollusks) and fish, is among the 4 most common food allergies causing anaphylaxis, but there are limited data showing SA clinical management in different countries. Objective: We sought to characterize a large cohort of patients with fish and shellfish allergy and to facilitate standardization of future care for this increasingly common allergic disease. Methods: We performed a retrospective, observational, noninterventional study from 945 patients from 2015 to 2019 in 7 hospitals in the United States and the United Kingdom to evaluate SA. A chi-square test was used to detect differences in family history, medical history, and current symptoms between patients in 2 countries. Results: Underdiagnosed anaphylaxis in patients with SA was associated with underuse of epinephrine (adrenaline) autoinjectors in both countries. Oral food challenge was used only when skin or serologic test results were negative. Asthma and allergic rhinitis were more common in the US patients with SA, but eczema was more common in UK patients with SA (P < .001). Respiratory, gastrointestinal, and neurological symptoms were higher in UK patients with SA than in US patients with SA (P < .001). Conclusions: In international multicenter cohorts of patients with fish and shellfish allergy, there are opportunities for improvement in management. Physician identification of anaphylaxis, use of diagnostic oral food challenges, and anaphylaxis treatment with epinephrine are areas with significant knowledge gaps in need of improvement in the United Kingdom and the United States. There is an opportunity for the development of unified, standardized diagnostic protocols for SA with distribution for allergists and trainees.

Background Insects often show adaptive phenotypic plasticity where environmental cues during early stages are used to produce a phenotype that matches the environment experienced by adults. Many tropical satyrine butterflies (Nymphalidae: Satyrinae) are seasonally polyphenic and produce distinct wet- and dry-season form adults, providing tight environment-phenotype matching in seasonal environments. In studied Mycalesina butterflies, dry-season forms can be induced in the laboratory by growing larvae at low temperatures or on poor food quality. Since both these factors also tend to reduce larval growth rate, larval growth rate may be an internal cue that translates the environmental cues into the expression of phenotypes. If this is the case, we predict that slower-growing larvae would be more likely to develop a dry-season phenotype. Methods We performed the first experimental study on seasonal polyphenism of a butterfly in the tribe Melanitini. We measured both larval growth rate and adult phenotype (eyespot size and wing shape) of common evening brown butterflies (Melanitis leda), reared at various temperatures and on various host-plant species. We constructed provisional reaction norms, and tested the hypothesis that growth rate mediates between external cues and adult phenotype. Results Reaction norms were similar to those found in Mycalesina butterflies. We found that both among and within treatments, larvae with lower growth rates (low temperature, particular host plants) were more likely to develop dry-season phenotypes (small eyespots, falcate wing tips). However, among temperature treatments, similar growth rates could lead to very different wing phenotypes, and within treatments the relationships were weak. Moreover, males and females responded differently, and eyespot size and wing shape were not strongly correlated with each other. Overall, larval growth rate seems to be weakly related to eyespot size and wing shape, indicating that seasonal plasticity in M. leda is primarily mediated by other mechanisms.

CD4+ T helper antigens are essential components of cancer vaccines, but the relevance of the source of these MHC class II-restricted antigens remains underexplored. To compare the effectiveness of tumor-specific versus tumor-unrelated helper antigens, we designed three DNA vaccines for the murine MC-38 colon carcinoma, encoding CD8+ T cell neoantigens alone (noHELP) or in combination with either “universal” helper antigens (uniHELP) or helper neoantigens (neoHELP). Both types of helped vaccines increased the frequency of vaccine-induced CD8+ T cells, and particularly uniHELP increased the fraction of KLRG1+ and PD-1low effector cells. However, when mice were subsequently injected with MC-38 cells, only neoHELP vaccination resulted in significantly better tumor control than noHELP. In contrast to uniHELP, neoHELP-induced tumor control was dependent on the presence of CD4+ T cells, while both vaccines relied on CD8+ T cells. In line with this, neoHELP variants containing wild-type counterparts of the CD4+ or CD8+ T cell neoantigens displayed reduced tumor control. These data indicate that optimal personalized cancer vaccines should include MHC class II-restricted neoantigens to elicit tumor-specific CD4+ T cell help.