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Mouse models are a critical tool for studying human diseases, particularly developmental disorders1. However, conventional approaches for phenotyping may fail to detect subtle defects throughout the developing mouse2. Here we set out to establish single-cell RNA sequencing of the whole embryo as a scalable platform for the systematic phenotyping of mouse genetic models. We applied combinatorial indexing-based single-cell RNA sequencing3 to profile 101 embryos of 22 mutant and 4 wild-type genotypes at embryonic day 13.5, altogether profiling more than 1.6 million nuclei. The 22 mutants represent a range of anticipated phenotypic severities, from established multisystem disorders to deletions of individual regulatory regions4,5. We developed and applied several analytical frameworks for detecting differences in composition and/or gene expression across 52 cell types or trajectories. Some mutants exhibit changes in dozens of trajectories whereas others exhibit changes in only a few cell types. We also identify differences between widely used wild-type strains, compare phenotyping of gain- versus loss-of-function mutants and characterize deletions of topological associating domain boundaries. Notably, some changes are shared among mutants, suggesting that developmental pleiotropy might be 'decomposable' through further scaling of this approach. Overall, our findings show how single-cell profiling of whole embryos can enable the systematic molecular and cellular phenotypic characterization of mouse mutants with unprecedented breadth and resolution.

Carola Santi,1 Thomas Haag,2 Christian Cooke,2 Michael E Schatman,3,4 Andrea Tinnirello5 1Anesthesia, Intensive Care and Pain Management Unit, Manerbio Hospital, ASST Del Garda, Brescia, Italy; 2Pain Management Unit-Wrexham Maelor Hospital, Wrexham, UK; 3Department of Anesthesiology, Perioperative Care, & Pain Medicine, NYU Grossman School of Medicine, New York, NY, USA; 4Department of Population Health – Division of Medical Ethics, NYU Grossman School of Medicine, New York, NY, USA; 5Anesthesia and Pain Management Unit, Iseo Hospital, ASST Franciacorta, Brescia, ItalyCorrespondence: Andrea Tinnirello, Ospedale di Iseo-Asst Franciacorta, Via Giardini Garibaldi 1, Iseo, BS, 25049, Italy, Tel +390303422, Email andrea.tinnirello@asst-franciacorta.itPurpose: Radiofrequency ablation has been used to treat chronic shoulder pain with mixed results. Thanks to recent anatomical studies, the precise location of articular branches of the suprascapular, lateropectoral and axillary nerves has been determined. Cooled radiofrequency is a neuroablative modality of treatment which has been demonstrated as efficient in different anatomical locations, and targeting the aforementioned nerves could result in a complete and efficient denervation of the shoulder. The aim of this study is to assess the efficacy of a fluoroscopic guided cooled radiofrequency technique for chronic shoulder pain.Patients and Methods: This is a retrospective observational study performed in two hospital in Wales and Italy (Wrexham NHS trust and Iseo Hospital). Forty-four patients were treated between December 2019 and January 2023. Follow-up was provided at 1-, 6- and 12-months post-procedure. Pain intensity was measured with a 0– 10-point Numerical Rating Scale (NRS), and was assessed at rest and during movement. Disability was assessed with the Oxford Shoulder Score (OSS). All patients were treated with cooled radiofrequency under fluoroscopic guidance targeting the articular branches of the suprascapular, axillary and lateropectoral nerves.Results: In the 44 patients treated, the mean NRS significantly decreased at all follow ups, pain relief of > 50% was obtained in 70.4%, 61% and 51% of the patients at 1.6 and 12 month follow-ups, respectively. Disability improved significantly, with a mean OSS at 12 months follow up of 30 ± 17.5, compared to 15 ± 3 at baseline. Medication intake (non-steroidal anti-inflammatory drugs (NSAIDS) and/or opioids) significantly decreased at all follow ups.Conclusion: Cooled radiofrequency denervation can be an effective procedure to manage chronic shoulder pain, providing sustained pain relief and functional improvement in more than 50% of the patients.Keywords: radiofrequency, neuromodulation, shoulder pain, pain management

This study aimed to describe orthodontic treatment patterns of children in Australia.

Identity construction during adolescence constitutes a primary psychosocial developmental task. A growing body of research has addressed the importance of school education in fostering adolescents' identity formation and the skills they need to thrive. Although several studies aimed at defining the factors contributing to a coherent, stable, and integrated identity formation, none sought to investigate this question from the adolescents' perspective. This contribution aimed to explore new ways of fostering 21st-century skills among adolescents through action research. Five adolescents aged 13 to 15 participated in the research process, creating a survey to answer a research problem mainly focused on identity construction in adolescence. A reflexive analysis of the co-research process highlighted the interest in involving adolescents as co-researchers to foster their social and emotional skills. The deployment of the resulting survey in a sample of 1210 adolescents from the general population highlighted the importance of gender diversity for constructing various dimensions of identity.

Skills and understanding of operations with negative numbers, which are typically taught in middle school, are crucial aspects of numerical competence necessary for all subsequent mathematics. To more swiftly and coherently develop the field's understanding of how to foster this critical competence, we need shared measures that allow us to compare results across studies with diverse populations and theoretical perspectives. Yet, to date no validated instrument exists to assess all four primary operations (addition, subtraction, multiplication and division). Thus, we conducted a Rasch analysis of the Integer Test of Primary Operations (ITPO) with 187 middle school students to provide a valid and reliable assessment with good person and item fit. The implications of this study are numerous for multiple stakeholders including scholars, test and textbook developers, as well as teachers. First, we validated three forms of the ITPO to foster future longitudinal studies of how integer arithmetic knowledge ismaintained or decays as well as how such knowledge might be related to success in STEM disciplines. Second, our analysis provides trustworthy insights about relative difficulty of integer problem structures because regardless of test form similar problem structures loaded together. For instance, sums of additive inverses were the easiest structure, whereas division by -1 was more difficult than multiplying or dividing by any other integer. We discuss each of these and other findings that have practical implications for learning and teaching integers. Third, for broader mathematics assessments in which minimal items can be included to measure integer knowledge, this study informs which items would serve the intended assessment purpose. Finally, we provide the three forms as an appendix in printable formats to ensure these validated tests are practical to implement for teachers as well as scholars.

Managers sometimes have a bad reputation as they are often perceived as more manipulative than other employees. This study focuses on the Dark Triad (DT)—comprising psychopathy, Machiavellianism, and narcissism—and its connection with managers’ “Ability” Emotional Intelligence (AEI). The link between DT (measured through the Dirty Dozen) and managers’ AEI (measured through QEPro, an AEI performance test) was examined through a Latent Profile Analysis (LPA). We identified two AEI latent profiles within a heterogeneous population of 231 French managers. Our results show that managers with the FEP (Full Emotional Processing) profile are less Machiavellian (relative to the MEP -Minimal Emotion Processing- profile). Our results show that identifying AEI profiles may be a practical way to prevent toxic Management.

The cut-open oocyte Vaseline gap technique is a powerful electrophysiological method for the characterization of ion channels. However, traditional amplifiers for cut-open oocyte Vaseline gap are labor intensive and require significant user expertise. We introduce an innovative, open-source digital amplifier system with high-speed digitization and software-controlled electronics for computer-driven automation. This system compares well to existing commercial systems in terms of conventional specifications of step response (current peak at 25μs and decay of 36μs time constant), current noise (1.0 nA at 3-kHz bandwidth), and dynamic range (96.9 dB). Additionally, it unlocks new methods through close integration of the amplifier and software, including machine-learning techniques for tuning capacitive compensation waveforms, achieving a 100-fold suppression of mean-squared transient current, and impedance measurement methods to identify system components such as membrane capacitance and electrode resistances. For future extensions, the design has unique attributes such as real-time digital signal processing for feedback, multiple input and multiple output, and allows for user customization. By providing open-source access to the circuit board designs, control software, and field-programmable gate array code on GitHub, this approach aims to foster cross-disciplinary collaboration and facilitate instrument customization enabling previously inaccessible electrophysiology experiments.

Abstract A systematic series of industrial‐relevant polystyrene‐based anion exchange resins that are functionalized with hydro‐ or fluorocarbon chains are compared regarding their adsorption behavior toward perfluorocarboxylic acids (PFCA) in respect to their charge, chain length, and type of chain. The results clearly show the dominance of electrostatic interactions in the adsorption process as uncharged adsorber materials showed no adsorption at all. In contrast, the charged adsorber materials showed in general a PFCA removal of 80% to 30% over the experiment depending on effluent fraction. Unexpectedly, for perfluorobutanoic acid (PFBA) the highest removal rate is found with consistently >90%. Despite observing significant benefits in the adsorption of PFCA for fluoroalkylated adsorbers in comparison to their non‐fluorinated counterparts, this effect of fluoroalkylation is comparatively small and can not be clearly attributed to fluorophilic interactions between the fluoroalkyl chains. These findings help clarifying that the introduction of fluorocarbon moieties in adsorber materials is not necessary in order to remove fluorocarbon molecules from the environment.

The control of plant diseases represents a significant challenge in agriculture, particularly with the current emphasis on reducing pesticide use, necessitating alternative approaches. Among them, resistant plant breeding programs offer a promising alternative. Considering the stressful conditions in space, space conditions emerge as an innovative method for advancing crop improvement. This study explored the unique potential of the International Space Station (ISS) environment to induce beneficial modifications in grapevine, resulting in plants with reduced susceptibility to diseases. Canes of two Vitis vinifera L. cultivars, Cabernet Sauvignon (CS) and Merlot (Me), have undergone a 10-month space journey on-board the ISS, while others stayed on Earth (Ground Control, GC). We conducted a 2-year analysis of the response to downy mildew (Plasmopara viticola) of plants developed from ISS and GC canes, called Mother plants. The disease development of progenies produced from Merlot Mother plants was also evaluated. A higher proportion of individuals with low-susceptibility was noted in the ISS Mother group compared to the controls for both cultivars. This trend was also observed for the Merlot progenies. Finally, 11% of Merlot individuals (Mother and progenies, and for the 2 years of study) were distributed in the low susceptibility class. This study suggests that grapevine canes exposure to ISS conditions resulted in an enhanced percentage of plants showing reduction of susceptibility to downy mildew.

Introduction Despite growing evidence of efficacy, oncology patient navigation is not ubiquitously offered. Navigation may reduce barriers to cancer care, yet geographic location may limit patient access. To overcome geographical barriers and increase patient education in oncology, our medical center developed a virtual navigation program. Objective To examine the efficacy of the Virtual Navigation Program designed to increase patient access and education across local and national contexts Methods In this mixed-methods study, a total of 105 individuals completed an online survey administered nationally to oncology patients who used the navigation program. Clinical and demographic data were collected. Nonparametric tests were used for group comparisons (Wilcoxon Signed-Ranks test). Results Virtual navigation increased access as the majority of patients utilized the Virtual Navigation Program beyond the local area; 42% of patients were local; 58% were patients located across the US. 55 (52%) were female; 25% were non-White. Pancreatic cancer was the largest tumor type: 51 (49%). Patients agreed the virtual cancer education helped them make critical health choices (mean 4.89 SD = 84); understand their diagnosis (mean 4.44 SD = .77); were able to make informed decisions (mean 4.43 SD = .83), and empowered to manage their cancer care (mean 4.58 SD = .82). Post navigation, the user experience survey revealed significant increases in a subset of patients’ cancer knowledge ( P

A holistic understanding and careful balancing of different quality aspects can support sustainable, evidence-based decisions during the planning and realisation phases of a building. To this end, it is important to consider, whether and to what extent different quality aspects are interrelated in order to assess potential consequences of decisions. For this purpose, the Holistic Quality Model 2.0 is introduced, representing a second iteration of the Holistic Quality Model developed in recent studies. It incorporates two improvements. First, the integration of the economic quality aspect in addition to the technical, environmental and social quality aspects. Second, the development of an extended interrelations methodology to facilitate better identification and quantitative analysis of interrelations. These improvements and a corresponding case study emphasise the shift from the conventional practice of evaluating quality aspects in isolation towards a holistic approach enabling informed decision-making by considering and balancing different quality aspects.