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Despite a significant accumulation of research, there has been little systemic implementation of evidence-based practices (EBP) in youth mental health care. The fragmentation of the evidence base complicates implementation efforts. In light of this challenge, we sought to pilot a system that consolidates and coordinates the entire evidence base in a single direct service model (i.e., Managing and Adapting Practice; MAP) in the context of a legal reform of psychotherapy training in Germany. This pilot study aimed to evaluate the feasibility of the implementation of MAP into the curriculum of the reformed German masters program. Eligible participants were students in the masters program at Philipps-University Marburg during the winter-term 2022/2023. Students first learned about MAP through introductions and role plays (seminar 1), followed by actively planning and conducting interventions using MAP resources for patients in a case seminar under supervision (seminar 2). A repeated-measures survey was conducted to investigate students knowledge gains, perception of MAP and changes in their self-rated confidence to use EBP. Results indicated that students perceive MAP to be manageable to learn. Positive progress was achieved with regard to their knowledge and self-reported confidence to use EBP, although interpretation and generalization of the results are limited by small and homogeneous samples, lack of statistical power and missing comparison groups. The feasibility of the implementation and suitability of measures are discussed. Important implications could be drawn with regard to future investigations.

Abstract Background Effective physician-patient communication is crucial to compassionate healthcare, particularly when conveying life-altering diagnoses such as those associated with congenital heart diseases. Despite its importance, medical practitioners often face challenges in communicating effectively. Because of these gaps, we aim to introduce a simulation-based training protocol to improve pediatric cardiology trainee’s communication skills. This study will be conducted in collaboration with associations supporting caregivers of children with congenital heart disease. It strives to demonstrate how specific training programs can efficiently foster humanistic, patient-centered care in standard medical practice. Methods This multicenter, open-label randomized controlled trial will be conducted in pediatric cardiac units and simulation centers of across 10 universities in France. The study population comprises pediatric cardiologists in training (including pediatric cardiac fellows or specialist assistants). The SIMUL-CHD intervention will consist of simulation-based training with standardized patients, focusing on improving communication skills for pediatric cardiology trainees during diagnostic counselling. Patients and caregivers have been recruited from a National Patient Association named “Petit Cœur de Beurre”. The primary outcome is the quality of physicians’ communication skills. The evaluation committee, which will review video recordings of the sessions, will be blinded to which participants received simulation-based training (group of interest) and which received theory-based training (control group). Secondary outcomes are the effect of SIMUL-CHD on empathy and anxiety levels in young pediatric cardiologists. Baseline scores pre and post-intervention will be compared, and skill improvement resulting from the intervention measured. Discussion Simulation-based training has proven efficacy in teaching technical skills in various scenarios however its application to communication skills in pediatric cardiology remains unexplored. The involvement of experienced parents provides a unique perspective, incorporating their profound understanding of the emotional challenges and specific hurdles faced by families dealing with congenital heart disease. Trial registration This trial is registered with the OSF registry (registered https://osf.io/ed78q ).

Establishing early academic momentum via credit accumulation is strongly associated with community college student success. Using data from one of the nation's largest and most racially diverse community college systems, our quasi-experimental study examined how different first-semester credit loads influenced persistence. For part-time students (less than 12 semester credit hours), enrolling in one additional course (3 more credits) significantly improved their chances of persistence to the subsequent term and next academic year. For part-time students, an increased credit load was significantly and positively related to persistence. However, for full-time students, an increase from 12 to 15 credits was not related to persistence. These patterns were consistent across subgroups by students' level of academic preparation (developmental education status) and degree objective (workforce credential or transfer associate degree). Moreover, the increased course load did not significantly hinder students' early academic performance as measured by GPA for any group and in some cases was related to increased GPA. We discuss the implications of these findings for academic advising, course scheduling, and completion initiatives at community colleges.

Academic advising has been described as the second-most important function in the community college (behind only instruction) toward helping students achieve their goals. Using interview data from 78 students and 33 advisors at one of the nation's largest and most racially diverse community college systems, our qualitative case study examined how academic advisors inform, and directly influence, students' enrollment decisions. Advisors emphasized their role as supporting and scaffolding student decision-making, but not making decisions for students. Most advisors endorsed a developmental approach focused on building students' knowledge and capacity to make better decisions about their own academic trajectory. However, some students had conflicting expectations of the advising relationship (e.g., advisors should tell them exactly what to study, which courses and how many to take), which resulted in frustration and desires for highly prescriptive advising. Advisors recognized a one-size-fits-all advising model would not work well for their diverse student population and rejected prescriptive recommendations, such as uniform advice that each student take 15 credit hours per semester. Instead, advisors considered the totality of each advisee's circumstances (e.g., background, academic preparation, goals, family and work life, transportation) when providing guidance on course load. But determining each student's optimal course load/combination was complicated by the wide range of academic and personal factors advisors had to consider. Consequently, most advisors accentuated the potential risks (for students and themselves) of advising students to attempt too heavy a course load.

Abstract Introduction Training novice ophthalmology residents on the EyeSi® simulator increases cataract surgery safety. However, there is no consensus regarding how much training residents should perform before their first time on patients. We evaluated the French national training program through the analysis of the learning curves of novice residents. Methods This prospective multicentric pedagogic study was conducted with French novice residents. Each resident completed the recommended four two-hour training sessions and performed a standardized assessment simulating standard cataract surgery before the first session (A0), at the end of the first (A1), second (A2), third (A3) and fourth (A4) sessions. For each surgical step of each attempt, the following data were collected: score, odometer, completion time, posterior capsular rupture and cumulative energy delivered (ultrasounds) during phacoemulsification. A performance threshold was set at a score of 80/100 for each surgical step, 400/500 for the overall procedure. Only descriptive statistics were employed. Results Sixteen newly nominated ophthalmology residents were included. Median score progressively increased from 95 [IQR 53; 147]) at A0 to 425 [IQR 411; 451] at A4. Despite a significant progression, the “emulsification” step had the lowest A4 scores 86 [IQR 60; 94] without reduction in completion time, odometer or ultrasounds delivered. The rate of posterior capsular rupture decreased linearly from 75% at A0 to 13% at A4 during “emulsification” and from 69 to 0% during “irrigation and aspiration”. At A4, only 25% [8; 53] of residents had > 80 at each step and only 75% [47; 92] had > 400/500 overall. Conclusion A training program consisting of four two-hour sessions on the EyeSi simulator over four consecutive days effectively enhances the surgical skills of novice ophthalmology residents. Undergoing more training sessions may improve scores and decrease the incidence of surgical complications, particularly at the emulsification step of cataract surgery. The learning curves presented here can reassure residents who are progressing normally and help identify those who need a further personalized training program. Trial registration ClinicalTrials registration number: NCT05722080 (first submitted 22/12/2022, first posted 10/02/2023).

Abstract Despite a significant accumulation of research, there has been little systemic implementation of evidence-based practices (EBP) in youth mental health care. The fragmentation of the evidence base complicates implementation efforts. In light of this challenge, we sought to pilot a system that consolidates and coordinates the entire evidence base in a single direct service model (i.e., Managing and Adapting Practice; MAP) in the context of a legal reform of psychotherapy training in Germany. This pilot study aimed to evaluate the feasibility of the implementation of MAP into the curriculum of the reformed German master's program. Eligible participants were students in the master’s program at Philipps-University Marburg during the winter-term 2022/2023. Students first learned about MAP through introductions and role plays (seminar 1), followed by actively planning and conducting interventions using MAP resources for patients in a case seminar under supervision (seminar 2). A repeated-measures survey was conducted to investigate students’ knowledge gains, perception of MAP and changes in their self-rated confidence to use EBP. Results indicated that students perceive MAP to be manageable to learn. Positive progress was achieved with regard to their knowledge and self-reported confidence to use EBP, although interpretation and generalization of the results are limited by small and homogeneous samples, lack of statistical power and missing comparison groups. The feasibility of the implementation and suitability of measures are discussed. Important implications could be drawn with regard to future investigations.

ABSTRACTHuman Milk Oligosaccharides (HMOs) have been proposed to be instrumental in building immune competence. To explore the role of HMOs in allergy prevention, twenty-one HMOs were quantified in breast milk samples and associated with sensitisation in infants. 2′-fucosyllactose (2′-FL) levels were positively associated with an increased risk of sensitisation, atopic dermatitis and recurrent skin rash. Interestingly, 2′-FL levels, ranging from 1.35 to 1.95 g/L, were associated with a higher prevalence of non-allergic and non-sensitised infants. The role of 2′-FL and lacto-N-neotetraose (LNnT) was further investigated in allergic sensitisation models in vivo. Oral administration of HMOs decreased allergic sensitisation. This was associated with gut microbiota and short-chain fatty acid (SCFA) production changes. Aligned with the clinical associations, the decreased sensitisation was not observed with lower and higher tested doses of the HMOs supporting a U-shape association between 2′-FL and LNnT levels and allergic sensitisation risk reduction in humans and mice.Trial registration: ClinicalTrials.gov identifier: NCT02550236.

Objectives: To understand why some long-term childhood cancer survivors experience positive adjustment in the long run,[Q1] this study aimed to (1) explore associations between well-being, health status, social support, and emotion regulation (ER) strategies in a cohort of long-term childhood lymphoblastic leukemia (cALL) survivors, (2) identify the individual contribution of each ER strategy to well-being (3) and their interaction with social support.Methods: We used data from 92 participants from the PETALE cohort (51% female, aged 24 ± 7 years). Measures included well-being (WHO-5), health status (15D), social support (SSQ-6), cognitive reappraisal and expressive suppression (ERQ), and emotional processing and expression (EAC). We modeled the odds of high well-being adjusting for health status in logistic regressions and explored the moderating role of social support with bootstrap techniques. Independent of clinical history, high well-being was associated with better health status, higher social support, more frequent use of cognitive reappraisal and emotional processing.Results: We found a main contribution of emotional processing to well-being (OR = 2.12, 95% CI = 1.09-5.37). The interaction between low suppression and high social support was significant (OR = .40, 95% CI = .13-.79). Probabilities for high well-being were 96% when expressive suppression was low and social support was high. Results suggest approaching one's own emotions may contribute to well-being in long-term childhood cancer survivors.Clinical implications: Combining curbing emotional suppression with promoting supportive social environment could be a promising target for future supportive care interventions in survivors.

Abstract Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Main body This selection of highlights provides commentary on 24 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application of novel radiopharmaceuticals. Conclusion Trends in radiochemistry and radiopharmacy are highlighted. Hot topics cover the entire scope of EJNMMI Radiopharmacy and Chemistry, demonstrating the progress in the research field in many aspects.

Abstract Marine organisms are simultaneously exposed to anthropogenic stressors associated with ocean acidification and ocean warming, with expected interactive effects. Species from different trophic levels with dissimilar characteristics and evolutionary histories are likely to respond differently. Here, we perform a meta-analysis of controlled experiments including both ocean acidification and ocean warming factors to investigate single and interactive effects of these stressors on marine species. Contrary to expectations, we find that synergistic interactions are less common (16%) than additive (40%) and antagonistic (44%) interactions overall and their proportion decreases with increasing trophic level. Predators are the most tolerant trophic level to both individual and combined effects. For interactive effects, calcifying and non-calcifying species show similar patterns. We also identify climate region-specific patterns, with interactive effects ranging from synergistic in temperate regions to compensatory in subtropical regions, to positive in tropical regions. Our findings improve understanding of how ocean warming, and acidification affect marine trophic levels and highlight the need for deeper consideration of multiple stressors in conservation efforts.

Abstract The gut microbiota modulates response to hormonal treatments in prostate cancer (PCa) patients, but whether it influences PCa progression remains unknown. Here, we show a reduction in fecal microbiota alpha-diversity correlating with increase tumour burden in two distinct groups of hormonotherapy naïve PCa patients and three murine PCa models. Fecal microbiota transplantation (FMT) from patients with high PCa volume is sufficient to stimulate the growth of mouse PCa revealing the existence of a gut microbiome-cancer crosstalk. Analysis of gut microbial-related pathways in mice with aggressive PCa identifies three enzymes responsible for the metabolism of long-chain fatty acids (LCFA). Supplementation with LCFA omega-3 MAG-EPA is sufficient to reduce PCa growth in mice and cancer up-grading in pre-prostatectomy PCa patients correlating with a reduction of gut Ruminococcaceae in both and fecal butyrate levels in PCa patients. This suggests that the beneficial effect of omega-3 rich diet is mediated in part by modulating the crosstalk between gut microbes and their metabolites in men with PCa.

Abstract Background Research has consistently shown that some children are more vulnerable at the time of school readiness. Better understanding the characteristics of these children is therefore important. Most studies have used a variable-based approach, which may mask the presence of small but important subgroups of children with mixed patterns of readiness strengths and weaknesses. Identifying subgroups with mixed readiness patterns using a person-centered approach matters because their developmental trajectories might differ in important ways from children with broader difficulties across all readiness domains. Objective This systematic review attempts to synthesize existing profiles of school readiness conducted on preschool-aged children and to describe how these various profiles are associated with children’s academic achievement and social adjustment during their school years. Specifically, we described how the school readiness profiles vary in number of profiles identified and differences in the specific domains of school readiness. We further describe the school readiness profiles and how they predict later academic and social outcomes. Furthermore, we focus on profile differences between at-risk and non-at-risk preschoolers. Methods Longitudinal studies published between 2005 and 2022 on profiles of school readiness before school entry and at least one subsequent academic and/or social outcomes were extracted from five databases. Eight articles were included in this systematic review out of the 117 screened peer-reviewed articles. Results All the studies incorporated both the cognitive and socioemotional domains of school readiness in their profiles. Fifteen profiles of school readiness at preschool age were identified based on the child level of cognitive and socioemotional skills, with 7 profiles at risk of later academic and social difficulties. Despite variation, children in these at-risk profiles of school readiness shared similar features. Conclusion This literature review provides an exhaustive summary on the number of profiles and domains of school readiness most frequently reported in studies using a person-centered approach. Yielding an in-depth description of at-risk profiles of school readiness can help designing early preventive intervention for these children.

BackgroundIn 2020, the Health Resources and Services Administration's HIV/AIDS Bureau funded an initiative to promote implementation of rapid antiretroviral therapy initiation in 14 HIV treatment settings across the U.S. The goal of this initiative is to accelerate uptake of this evidence-based strategy and provide an implementation blueprint for other HIV care settings to reduce the time from HIV diagnosis to entry into care, for re-engagement in care for those out of care, initiation of treatment, and viral suppression. As part of the effort, an evaluation and technical assistance provider (ETAP) was funded to study implementation of the model in the 14 implementation sites.MethodThe ETAP has used implementation science methods framed by the Dynamic Capabilities Model integrated with the Conceptual Model of Implementation Research to develop a Hybrid Type II, multi-site mixed-methods evaluation, described in this paper. The results of the evaluation will describe strategies associated with uptake, implementation outcomes, and HIV-related health outcomes for patients.DiscussionThis approach will allow us to understand in detail the processes that sites to implement and integrate rapid initiation of antiretroviral therapy as standard of care as a means of achieving equity in HIV care.

Abstract Background Neural tube defects (NTDs) are caused by genetic and environmental factors. ARMC5 is part of a novel ubiquitin ligase specific for POLR2A, the largest subunit of RNA polymerase II (Pol II). Results We find that ARMC5 knockout mice have increased incidence of NTDs, such as spina bifida and exencephaly. Surprisingly, the absence of ARMC5 causes the accumulation of not only POLR2A but also most of the other 11 Pol II subunits, indicating that the degradation of the whole Pol II complex is compromised. The enlarged Pol II pool does not lead to generalized Pol II stalling or a generalized decrease in mRNA transcription. In neural progenitor cells, ARMC5 knockout only dysregulates 106 genes, some of which are known to be involved in neural tube development. FOLH1, critical in folate uptake and hence neural tube development, is downregulated in the knockout intestine. We also identify nine deleterious mutations in the ARMC5 gene in 511 patients with myelomeningocele, a severe form of spina bifida. These mutations impair the interaction between ARMC5 and Pol II and reduce Pol II ubiquitination. Conclusions Mutations in ARMC5 increase the risk of NTDs in mice and humans. ARMC5 is part of an E3 controlling the degradation of all 12 subunits of Pol II under physiological conditions. The Pol II pool size might have effects on NTD pathogenesis, and some of the effects might be via the downregulation of FOLH1. Additional mechanistic work is needed to establish the causal effect of the findings on NTD pathogenesis.

This study focuses on the synthesis of Biguanide-PROTACs, formed by conjugating the biguanide motif with a spacer and a ligand for recognition subunits of two E3 ubiquitin ligases. Evaluation of their activity on pancreatic cancer cell (KP4) proliferation established a correlation between membrane permeability and median effective concentration. Mechanistic insights revealed that only two compounds exhibited biguanide-like AMPK activation, while only one hydrophobic compound uniquely altered mitochondrial protein levels. The prospect of developing and expanding the Biguanide-PROTAC library holds several promises, offering potential insights into biguanide mechanisms and the creation of more potent anticancer agents. This study contributes to understanding the intricate interplay between compound structure, permeability, and anticancer activity, paving the way for targeted drug development in pancreatic cancer treatment.