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Mindfulness witnessed a substantial popularity surge in the past decade, especially as digitally self-administered interventions became available at relatively low costs. Yet, it is uncertain whether they effectively help reduce stress. In a preregistered (OSF https://doi.org/10.17605/OSF.IO/UF4JZ ; retrospective registration at ClinicalTrials.gov NCT06308744 ) multi-site study (nsites = 37, nparticipants = 2,239, 70.4% women, Mage = 22.4, s.d.age = 10.1, all fluent English speakers), we experimentally tested whether four single, standalone mindfulness exercises effectively reduced stress, using Bayesian mixed-effects models. All exercises proved to be more efficacious than the active control. We observed a mean difference of 0.27 (d = -0.56; 95% confidence interval, -0.43 to -0.69) between the control condition (M = 1.95, s.d. = 0.50) and the condition with the largest stress reduction (body scan: M = 1.68, s.d. = 0.46). Our findings suggest that mindfulness may be beneficial for reducing self-reported short-term stress for English speakers from higher-income countries.

Abstract Purpose To assess the efficacy of bolus injections of landiolol hydrochloride as premedication in coronary artery CT angiography (CCTA). Methods The study population consisted of 37 patients (17 female; median age, 56 years; IQR, 19 years; range, 19–88 years) who underwent CCTA after intravenous injection of landiolol hydrochloride due to a heart rate > 60 bpm. Landiolol hydrochloride was administered in a stepwise manner until a heart rate of ≤ 60 bpm was achieved or a maximum dose of 60 mg was reached after six injections. Heart rates routinely displayed continuously on the CT scanner before the start of the landiolol hydrochloride injection (HRPRE), after each partial dose (HR1–6), during the CT scan (HRCT), and after the examination before moving from the CT table (HRPOST) were recorded. Furthermore, the blood pressure routinely measured before (BPPRE) and after the examination before moving from the CT table (BPPOST) was recorded. Results A HRCT of ≤ 60 bpm was achieved in 13 patients (35%) and a HRCT ≤ 65 bpm was achieved in 25 patients (68%). The mean difference (± SD) between HRPRE and HRCT was −11 ± 9 bpm in total, −14 ± 10 bpm in patients without oral beta-blocker premedication and −6 ± 5 bpm in patients with oral Beta-blocker premedication. Conclusions Landiolol hydrochloride enables a reduction of the heart rate in patients with and without oral beta-blocker premedication, whereby the use of serial partial doses is a simple and effective approach in clinical routine. Critical relevance statement In cardiac CT, weight-independent, stepwise landiolol hydrochloride injection up to 40 mg reduces heart rate by −14 bpm without and −5 bpm with oral beta-blocker premedication, and achieves heart rates of ≤ 65 bpm in a significant proportion of patients. Key Points The ideal heart rate for cardiac CT is ≤ 60–65 bpm, which improves image quality and reduces radiation dose. In cardiac CT, landiolol hydrochloride intravenously reduces heart rate by −14 bpm. Heart rate of ≤ 65 bpm can be achieved in a significant proportion of patients. Graphical Abstract

Abstract Background Virtual surgical planning for orthognathic surgery typically relies on two methods for intraoperative plan transfer: CAD/CAM occlusal splints and patient-specific implants (PSI). While CAD/CAM splints may offer limited accuracy, particularly in the vertical dimension, PSIs are constrained by higher costs and extended preparation times. Surgical navigation has emerged as a potential alternative, but existing protocols often involve invasive registration or lack transparent evaluation. This study introduces a novel protocol for point-based optical navigation using modified CAD/CAM splints for non-invasive registration and transparent intraoperative evaluation, assessing its effectiveness in maxillary positioning. Methods This prospective case-control study included 20 patients undergoing bimaxillary orthognathic surgery. The experimental group employed surgical navigation with modified CAD/CAM splints, while the control group used standard CAD/CAM splints. Surgical accuracy was evaluated by measuring translational and rotational discrepancies between the planned and achieved maxillary positions. A mixed ANOVA was conducted to assess other factors, aside from surgical navigation, that might influence surgical accuracy. Results Surgical navigation significantly improved accuracy in translational movements along the x-axis (right-left: -0.81 mm; p = 0.021) and z-axis (down-up: -0.82 mm; p = 0.014), as well as in yaw rotation (-0.45°; p = 0.045). Other movements also showed improved precision in the navigated group, though not statistically significant; y-axis (back-front): -0.60 mm (p = 0.094); pitch rotation: -0.70° (p = 0.071); roll rotation: -0.04° (p = 0.428). Besides the use of surgical navigation, the amount of planned movement significantly impacted surgical accuracy, although no specific factors could be identified to predict which cases would particularly benefit from surgical navigation. Conclusions Surgical navigation with modified CAD/CAM splints enhances surgical accuracy without requiring invasive procedures, offering a straightforward and transparent protocol suitable for routine clinical practice that allows intraoperative evaluation of maxillary positioning. However, the clinical significance and cost-effectiveness compared to PSI need further investigation. These findings suggest new directions for future developments, especially with advancements in mixed reality technologies, which could broaden the application of surgical navigation. Trial registration Retrospectively registered with the German Clinical Trials Register (DRKS00034795).

Abstract Background Exergames are interactive technology-based exercise programs. By combining physical and cognitive training components, they aim to preserve independence in older adults and reduce their risk of falling. This study explored whether primary end users (PEU, healthy older adults and patients with neurological and geriatric diagnoses) and secondary end users (SEU, health professionals) evaluated the ExerG functional model to be usable, providing a positive experience and therefore acceptable. Methods We conducted a multi-methods study using several assessments to quantify usability and enjoyment outcomes, along with semi-structured interviews to gain an in-depth understanding of the users’ experiences. Descriptive statistics were used for quantitative outcome measures. For qualitative data, a thematic analysis (TA) using an inductive, data-driven approach was carried out to develop themes for each user group. Results We interviewed 20 PEUs (13 healthy older adults, 7 patients) and 22 SEUs at two rehabilitation centres in Austria and Switzerland. Users' scores of over 70 on the System Usability Scale denoted good usability. On the Physical Activity Enjoyment Scale-16, both PEU groups rated the ExerG highly. Our TA approach identified four themes per user group. Themes from both PEU groups confirmed their enjoyment of training with the ExerG, however more variety and greater challenges were requested. Whilst the patient group appreciated the security given by the harness system, the healthy older adults reported feeling restricted. SEU themes reflected their approval of this novel training device, although a desire for increased difficulty and more individualisation was expressed. Clear instructions and an easy-to-use harness system were acknowledged and useful feedback for the developers emerged. Conclusions The ExerG is usable, offers a positive experience, and can therefore be regarded as an acceptable solution for the combined physical and mental training of older adults. Our findings contribute to the ongoing development of the ExerG, which will be a welcome addition to current training options for this target group. Further research is needed to confirm its effectiveness in preserving or improving functional independence in daily life and reducing the risk of falling.

Abstract In regenerating tissues, synthesis and remodeling of membranes rely on lipid turnover and transport. Our study addresses lipid adaptations in intestinal regeneration of Drosophila melanogaster and limb regeneration of Ambystoma mexicanum. We found changes in lipid profiles at different locations: transport, storage organs and regenerating tissues. We demonstrate that attenuating insulin signaling, exclusively in fat storage, inhibits the regeneration-specific response in both the fat storage and the regenerating tissue in Drosophila. Furthermore, in uninjured axolotls we found sex-specific lipid profiles in both storage and circulation, while in regenerating animals these differences subside. The regenerating limb presents a unique sterol profile, albeit with no sex differences. We postulate that regeneration triggers a systemic response, where organs storing lipids play a significant role in the regulation of systemic lipid traffic. Second, that this response may be an active and well-regulated mechanism, as observed when homeostatic sex-differences disappear in regenerating salamanders.

In an EEG-based near real-time neurofeedback (NF) study in two parts using high immersive virtual reality (VR) we successfully trained healthy participants to downregulate their parietal alpha power, a neurophysiological correlate previously associated with enhanced sense of presence. The first part included n = 10 participants equipped with 128 and 64 channels gel-based active EEG electrodes in 10 sessions using standard bar feedback presented on a computer monitor. Nine participants were better than random at the 10th session and four improved over time. For the second part we reduced the electrode subset to 9 sponge-based active channels (2 frontal, 7 parietal around Pz) and a portable amplifier. Participants (n = 10) were trained each session within VR using bar feedback projected on a wall in the first 5 sessions and then controlling the flow of a water fountain. Participants were able to significantly downregulate their parietal alpha power after 5 sessions and learning occurred at the group level, with 7 participants showing both improvement over time and ability to modulate. However, these results were only shown during the fountain feedback and both ability and learning were non-significant in the VR projector condition. Based on self-reports, after excluding participants performing movements and closing their eyes, no particular mental strategy, such as relaxation, breathing or mental calculus was identified to help with alpha modulation. The hypothesized behavioral effect on sense of presence was not found nor any neurophysiological changes in fronto-parietal connectivity. While NF did not improve the sense of presence, we succeeded in adapting real-time NF training for high immersive VR technology via seamlessly embedded feedback in the form of a water fountain. The study showcases that NF is possible with sponge electrodes and portable EEG that would prove convenient in end-user (at home) or clinical setup. The dataset is publicly available on Openneuro.org.

In acute myeloid leukemia (AML), leukemogenesis depends on cell-intrinsic genetic aberrations and thus, studies on AML require investigations in an in vivo setting as provided by patient derived xenografts (PDX) models. Here we report that, next to leukemic cell characteristics, recipient sex highly influences the outgrowth of AML cells in PDX models, with females being much better repopulated than males in primary as well as secondary transplantation assays. Testosterone may be the more important player since, strikingly, better engraftment was seen in castrated versus control male recipients, while ovariectomy did not significantly impair engraftment in females. Shorter time-to-engraftment and mouse survival were observed with adverse molecular risk, and respectively with high FLT3-ITD ratio mutated AML cells. Adverse risk AML furthermore showed higher percentages of phenotypic leukemic stem cells (LSCs), suggesting impaired differentiation capacity in these AML subtypes. Overall, we achieved successful repopulation with 14/23 (61%) favorable, 18/30 (60%) intermediate and 4/8 (50%) adverse risk AML cases in female recipient PDX models. Our data identify recipient sex as an important experimental confounder in leukemia PDX models, and the contribution of the sex hormones to leukemogenesis as an intriguing, underexplored research area.

Thin layer activation (TLA) is already routinely utilised for online wear monitoring of metallic components with the radioisotope concentration (RIC) method for various tribological applications. However, many components in tribological systems are made of carbon-based bulk material (e.g. polymers) or have carbon-based wear resistant coatings (e.g. diamond-like carbon). By utilising the nuclear reaction 12C(3He,x)7Be, TLA can thus be employed in carbon-containing components. To evaluate the applicability of this approach for TLA in combination with the RIC method, three materials EPDM (ethylene propylene diene monomer), PEEK (polyether ether ketone) and DLC (diamond-like carbon), which are vastly utilised in tribology, were activated. Subsequently, the modulus of elasticity and hardness of the activated specimens were measured and evaluated if the material works for TLA. As EPDM developed cracks after the irradiation process, it is regarded to be not applicable for TLA and subsequent wear measurements. While the PEEK material revealed small changes in hardness values compared to non-irradiated samples, the irradiated DLC coating showed no detectable material changes. Both irradiated materials have been applied to representative tribological wear studies, for which the RIC results showed a good correlation with optical wear measurements.

Karolin Teichmüller,1,2 Andrea Kübler,2 Heike L Rittner,1 Gudrun-Karin Kindl1 1University Hospital Würzburg, Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, Centre for Interdisciplinary Pain Medicine, Würzburg, Germany; 2University of Würzburg, Institute of Psychology, Department of Psychology I, Würzburg, GermanyCorrespondence: Gudrun-Karin Kindl, University Hospital Würzburg, Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, Centre for Interdisciplinary Pain Medicine, Oberdürrbacher Str. 6, Würzburg, 97080, Germany, Email Kindl_G@ukw.dePurpose: The Avoidance-Endurance Model postulates fear-avoidance responses and endurance responses as important psychological mechanisms in the development and maintenance of chronic pain. The present study aims to investigate potential differences in avoidance and endurance responses to pain before and with advanced chronification.Patients and Methods: Two samples of adults with non-cancer pain at two different stages of chronicity were compared: One with pain and risk factors for chronicity (n=26, part of the PAIN2020 project) and one with chronic pain (n=33 from a pain day care clinic). The German Pain Questionnaire, the Graded Chronic Pain Scale (GCPS) and medical reports were used to measure duration and severity of pain. Responses to pain were assessed with the Avoidance-Endurance Questionnaire (AEQ) and psychological strain with the Depression, Anxiety and Stress Scales (DASS).Results: Both groups were primarily affected by musculoskeletal pain. Although not yet chronified, the risk group reported comparable GCPS levels of pain intensity and disability. Depression and stress ratings were also similar, except for anxiety, which was significantly elevated in the chronic pain sample (p< .001). The AEQ scales did not differ between groups, neither on any of the fear-avoidance- nor endurance-related dimensions. A post-hoc regression analysis revealed a significant prediction of fear-avoidance by pain-related disability (p< .001). The regression model for endurance responses was not significant.Conclusion: Patients with risk factors of chronification experience substantial pain-related burden. Responses to pain in the realm of the Avoidance-Endurance model do not appear to vary as a function of chronification. While fear-avoidance and pain-related disability correlate positively, endurance could not be associated to any of our variables.Keywords: Avoidance-Endurance Model, fear-avoidance, chronic pain, chronification, PAIN2020

ObjectiveIn severe cases of systemic sclerosis (SSc), autologous hematopoietic stem cell transplantation (aHSCT) is superior compared to cyclophosphamide. But treatment related morbidity and mortality have to be considered. To date, data on major physical and psychological impacts of aHSCT are scarce. Therefore, subjectively experienced physical and psychological impact of aHSCT and exploration of internal and external factors helping to cope with aHSCT was assessed.MethodsRetrospective assessment of physical and psychological variables in an SSc cohort after aHSCT to describe: Health-related quality of life (HRQL), SSc-associated impairment, coping strategies, body image, and resilience. Additionally, semi-structured interviews were conducted and analyzed via mixed methods qualitative content analysis.ResultsThirty-two patients were included. HRQL correlated with impairment due to SSc and with depressive coping. An unfavorable body image correlated with reduced HRQL and increased impairment but improves after aHSCT. Patients with good resilience had a better HRQL, less depressive coping, and less SSc-associated impairment. The semi-structured interviews revealed that resilience is important for a successful disease management as patients with higher resilience were more satisfied with aHSCT, patients with lower resilience would have wished for more psychological support. Thirty-one patients would recommend aHSCT to other patients.ConclusionA transient negative impact of aHSCT on mental well-being is present but can be relieved by a team specialized to aHSCT. Psychological support seems to be an unmet need, particularly in patients with low resilience. Patients with higher resilience described a lower negative impact caused by aHSCT and higher satisfaction after therapy.

The use of hypofractionated radiotherapy in prostate cancer has been increasingly evaluated, whereas accumulated evidence demonstrates comparable oncologic outcomes and toxicity rates compared to normofractionated radiotherapy. In this prospective study, we evaluate all patients with intermediate-risk prostate cancer treated with ultrahypofractionated (UHF) MRI-guided radiotherapy on a 1.5 T MR-Linac within our department and report on workflow and feasibility, as well as physician-recorded and patient-reported longitudinal toxicity. A total of 23 patients with intermediate-risk prostate cancer treated on the 1.5 T MR-Linac with a dose of 42.7 Gy in seven fractions (seven MV step-and-shoot IMRT) were evaluated within the MRL-01 study (NCT04172753). The duration of each treatment step, choice of workflow (adapt to shape-ATS or adapt to position-ATP) and technical and/or patient-sided treatment failure were recorded for each fraction and patient. Acute and late toxicity were scored according to RTOG and CTC V4.0, as well as the use of patient-reported questionnaires. The median follow-up was 12.4 months. All patients completed the planned treatment. The mean duration of a treatment session was 38.2 min. In total, 165 radiotherapy fractions were delivered. ATS was performed in 150 fractions, 5 fractions were delivered using ATP, and 10 fractions were delivered using both ATS and ATP workflows. Severe acute bother (G3+) regarding IPS-score was reported in five patients (23%) at the end of radiotherapy. However, this tended to normalize and no G3+ IPS-score was observed later at any point during follow-up. Furthermore, no other severe genitourinary (GU) or gastrointestinal (GI) acute or late toxicity was observed. One-year biochemical-free recurrence survival was 100%. We report the excellent feasibility of UHF MR-guided radiotherapy for intermediate-risk prostate cancer patients and acceptable toxicity rates in our preliminary study. Randomized controlled studies with long-term follow-up are warranted to detect possible advantages over current state-of-the-art RT techniques.