Building a cardiac digital twin relies on high fidelity electrocardiogram signals to accurately simulate individual cardiovascular function. However, conventional ECG acquisition is not well suited for long term, unobtrusive home monitoring, while photoplethysmography, despite its advantage in continuous collection, lacks electrophysiological information. To bridge these complementary modalities for computational analysis, we propose MAGIC, a multi-grained conditional diffusion framework for generating ECG-like waveforms from PPG. MAGIC separates conditional information into a global condition and token-wise local conditions: the former summarizes segment-level cardiovascular context and modulates the diffusion Transformer through adaptive layer normalization, while the latter preserves patch-level PPG cues and is injected through gated cross-attention. The conditional encoder is pre-trained with paired PPG and ECG signals using ROI-weighted reconstruction, contrastive learning, and latent alignment, so that PPG-derived conditions are explicitly encouraged to match ECG-derived representations. Across four public datasets and four downstream proxy tasks, MAGIC improves distributional fidelity in most settings and shows competitive task-level utility. In representative analyses, pre-training reduces FD from 0.908 to 0.693 on MIMIC-AFib; MAGIC also achieves lower FD with 50 sampling steps than RDDM with 500 steps.
A fundamental problem in fault-tolerant quantum computation is the tradeoff between universality and dimensionality, exemplified by the Bravyi-König bound for n-dimensional topological stabilizer codes. In this Letter, we extend topological Pauli stabilizer codes to a broad class of n-dimensional Clifford hierarchy stabilizer codes. These codes correspond to the (n+1)D Dijkgraaf-Witten gauge theories with non-Abelian topological order. We construct transversal non-Clifford gates through automorphism symmetries represented by cup products. In 2D, we obtain the first transversal non-Clifford logical gates including t and cs for Clifford stabilizer codes, using the automorphism of the twisted Z_{2}^{3} gauge theory (equivalent to D_{4} topological order). We also combine it with the just-in-time decoder to fault-tolerantly prepare the logical t magic state in O(d) rounds via code switching. In 3D, we construct a transversal logical sqrt[T] gate in a non-Clifford stabilizer code at the third level of the Clifford hierarchy, located on a tetrahedron corresponding to a twisted Z_{2}^{4} gauge theory. Our constructions surpass the Bravyi-König bound by achieving the logical gates in the (n+1)th level of Clifford hierarchy in n spatial dimension.
Background Hematoma recurrence and progression remain common challenges in nonacute subdural hematomas (SDHs). The understanding of indications for middle meningeal artery embolization (MMAE) is limited. Purpose To investigate the utility of the hyperdense capsule sign (HDCS) at noncontrast CT for identifying potential candidates for MMAE for nonacute SDH. Materials and Methods In this post hoc analysis of the MAGIC-MT randomized controlled trial (September 2022 to December 2023) comparing adjunctive MMAE and usual care, participants were grouped by HDCS presence or absence at noncontrast CT. The primary outcome was symptomatic recurrence or progression of SDH. The Cochran-Mantel-Haenszel χ2 test, propensity score matching (PSM), multivariable analysis, and P value for interaction were used for subgroup comparisons. Results Among 697 participants included in this analysis (median age, 69 years [IQR, 61-74 years]; 575 male participants), 444 (63.7%) showed HDCS presence. Primary outcome incidence was lower in the embolization versus usual-care group among participants with the HDCS (5.0% vs 12.0%, P = .009; after PSM: 4.1% vs 11.2%, P = .04) but not among those without the HDCS (9.4% vs 5.6%, P = .24; after PSM: 10.3% vs 5.0%, P = .13), with an interaction between MMAE and HDCS presence (P = .01; after PSM: P = .01). The proportion of participants experiencing a serious adverse event was lower in the embolization versus usual-care group among those with the HDCS (5.9% vs 15.1%, P = .002; after PSM: 5.8% vs 15.5%, P = .02) but not among those without the HDCS (8.7% vs 5.6%, P = .34; after PSM: 9.4% vs 5.8%, P = .30), with a significant interaction (P = .01; after PSM: P = .02). Conclusion For participants with nonacute SDH, the presence of the HDCS was associated with a lower rate of recurrence or progression among those who underwent MMAE compared with those receiving usual care. HDCS may potentially help identify candidates for MMAE for nonacute SDH. Clinical trial registration no. NCT04700345 © RSNA, 2026 Supplemental material is available for this article. See also the editorial by Kallmes in this issue.
A gas-loading system compatible with ultrafast magic-angle spinning for solid-state nuclear magnetic resonance was developed to enable high-resolution proton detection of porous materials in a controlled gas atmosphere. Application to CO2 adsorption by a representative flexible metal-organic framework provided direct observation of site-specific host-guest interactions.
暂无摘要（点击查看详情）
While it has been one of the most important new physics discoveries in the last decade, the nature of superconductivity in the twisted graphene family remains an unsolved problem. Motivated by recent scanning tunneling experiments that report Kekulé ordering in moiré graphene superconductors, we develop a microscopic theory of this superconductivity for the twisted bilayer system. The pairing we find is an intra-valley, finite-momentum pair-density wave (PDW) that intrinsically carries a Kekulé modulation. This state exhibits four salient features: (i) spontaneous breaking of C3 rotation symmetry, producing nematic order; (ii) triplet pairing; and (iii) a quasiparticle density of states that evolves from a V-shaped profile to a fully gapped, U-shaped spectrum as the attraction increases, which is accompanied by (iv) systematic behavior of the temperature dependent zero bias conductance. These features align with key experimental signatures. We find, as well, that with only modest interaction strengths, the state is near to a BEC-like phase, consistent with the observed extremely short coherence lengths. Taken together, these results identify a microscopic intra-valley Kekulé PDW as a compelling candidate for unconventional superconductivity in the twisted graphene family.
Preference research has shown that humans have a bias towards items located in the middle of the visual field and a number of theories have been suggested to explain the phenomenon. The conjuring trick known as the placement force not only exploits this central bias but also shows that the preference is subtly biased to the right of centre. We used the force, together with eye tracking, to test the different theories. In a single experiment, four face-down playing cards were presented on a table in a horizontal row. Participants (n = 137) were asked to select one by pushing it forward. Results replicated the basic force effect showing that 52% of participants chose the middle right card. Eye tracking measures revealed that when participants fixated the cards, more time was spent looking at the two centrally located cards. However, this attentional bias did not predict the card they chose. Furthermore, individuals who were more reflective decision makers (as measured with the Cognitive Reflection Test) were no less susceptible to the force, nor were individuals who spent more time deliberating about their decision or those who examined more alternatives. The results do not support the view that central bias effects result from cognitive decision heuristics nor attentional biases. Instead, participants chose options that required the least physical effort. This supports the reachability hypothesis.
The chemical richness of RNAs is greatly enhanced by post-transcriptional modifications with RNA methylation as the most prominent type. RNA modifications modulate the stability, folding and interaction pattern of RNA molecules. Furthermore, emerging data suggests RNA modifications also directly regulate the activity of catalytic RNA molecules, i.e., ribozymes. Here, we employ classical and hybrid quantum-classical (QM/MM) molecular dynamics (MD) simulations to investigate the reaction mechanism of an artificial methyltransferase ribozyme MTR1. Importantly, we pinpoint how 2'-O-methylations of active site nucleotides synergistically enhance ribozyme activity by reducing the conformational flexibility of the ribose rings and rigidifying the active site. Finally, the herein reported crystal structure of the modified MTR1, solved at 2.6 Å resolution, validates the results of our simulations. Taken together, our work supports the purported central role of modified RNA for early RNA catalysis and may guide rational design of more efficient ribozymes.
Gel dosimeters have traditionally been developed for external beam radiotherapy and high-energy photon applications. However, their use in low-energy photon contexts-such as low-dose-rate (LDR) brachytherapy-remains limited by challenges related to temporal and thermal stability, as well as water equivalency. This study aimed to develop a novel dosimetric gel adapted to low-energy photon emissions from isotopes such as125I and to evaluate its performance using radioactive seeds incorporated into mock low-dose-rate 3D-printed brachytherapy implants for eye cancer treatments. A gel formulation composed of methacrylic and ascorbic acid in gelatin, known as MAGIC, was optimized using agarose (MAGIC-a) and paraformaldehyde (MAGIC-pf). The gel's thermal and temporal stability and self-polymerization were assessed using magnetic resonance imaging (MRI) and nuclear magnetic resonance (NMR) relaxometry. Water equivalency was evaluated using Monte Carlo (MC) simulations. The radiation sensitivity of MAGIC-pf gel to125I seeds was experimentally measured over two-days, followed by MRI readouts at 1.5T and 3T. For comparison, the gel's sensitivity to a high-energy, high-dose-rate (HDR)192Ir source was also assessed. Dose distributions were evaluated using 3D-printed polymer episcleral plaques. MAGIC-pf demonstrated superior thermal and temporal stability, along with enhanced MRI readout performance. Sensitivity values of MAGIC-pf exposed to125I seeds ranged from 0.155 to 0.388 Gy-1.s-1at 1.5T, and from 0.1 to 0.386 Gy-1.s-1at 3T. The gel's sensitivity to a192Ir source yielded 0.786 Gy-1.s-1at 1.5T. 3D-printed polymer episcleral plaques containing three125I seeds with asymmetric radiation emission profiles produced highly reproducible and geometrically precise dose distributions, visualized in 2D and 3D. MAGIC-pf gel demonstrated excellent temporal and thermal stability, compatibility with HDR and LDR brachytherapy applications, and water equivalency under investigated conditions. The sub-millimetric dose profiles it enables are well-suited to the precision demands of next-generation personalized 3D-printed brachytherapy implants.
'Smart tattoos' based on stimulus-responsive nanoparticles have emerged as a promising platform for intradermal biosensing and dynamic optical interfaces, yet translation to safe and sustained use in human skin remains largely untested. We report a pilot clinical evaluation of Magic Ink, a rewritable photochromic tattoo ink comprising nano-engineered pigments that switch reversibly between nearly colorless and magenta states under visible and ultraviolet light, enabling permanent intradermal tattoos to be visually erased and restored on demand. Preclinical studies established third-party-verified sterility and non-cytotoxicity, confirmed nanoparticle size/morphology and shear-thinning rheological behavior suitable for intradermal delivery, and demonstrated robust photochromic performance with rapid switching kinetics and high fatigue resistance. In a paired, within-subject study, 11 participants received matched Magic Ink and commercial 'Standard Ink' control tattoos. Healing outcomes were assessed by clinical inspection (days 7 & 21), participant surveys through day 21, and longitudinal photographic documentation over five months. No adverse events were observed (0/11 per group). Dermatologist assessments and participant-reported symptoms of pain, redness, and itch did not differ significantly between Magic Ink and Standard Ink tattoos. Magic Ink tattoos remained nearly imperceptible in the deactivated state yet became readily visible upon UV activation after at least one year in vivo, demonstrating durable retention of photoswitchable function in human skin. These results indicate that photo-rewritable tattoo nanomaterials can function as tolerable intradermal implants over the timescales examined, and support their further evaluation for dynamic or 'disappearing' tattoos in medical (e.g., radiotherapy treatment localization and biopsy site marking in dermatology), cosmetic and paramedical (e.g., permanent makeup and micropigmentation), and body art applications.
To describe the multidisciplinary management and outcomes of patients with vascular graft and endograft infections of the abdominal aorta (aVGEI) in Eastern Denmark. Retrospective cohort study of aVGEI patients between 1st July 2022 and 30th June 2025. Diagnosis and management were based on a multidisciplinary team (MDT) conference. The primary outcome was 90-day mortality. Secondary outcomes included one-year mortality, cure, remission, treatment failure, and re-hospitalization. In 35 aVGEI patients, the median age was 73 years (IQR 69.5-79 years), and the median Charlson Comorbidity Index score was 5 (IQR 3-6). The Management of Aortic Graft Infection Collaboration (MAGIC) criteria were fulfilled in 27 cases (77%, 'MAGIC positive aVGEI'). The remaining eight cases (23%) were based on conference consensus, often supported by positive PET-CT findings (n = 4/8). The most frequent monomicrobial infections were Staphylococcus aureus (n = 5/35, 14.3%) and coagulase-negative staphylococci (n = 4/35, 11.4%). Polymicrobial infections occurred in nine patients (25.7%). Five aVGEI patients were treated surgically (14.3%). The 90-day mortality was 8.6% (n = 3/35, 95%CI 1.8-3.1%); 4.2% among 'MAGIC positive aVGEI' patients (n = 1/24), 12.5% among those diagnosed on conference consensus (n = 1/8), and 33.3% among patients with an aortoenteric fistula (AEF) (n = 1/3). Among aVGEI patients with complete follow-up, cure was achieved in 31.8% (n = 7/22, 95%CI 13.9-4.9%), but none of the three patients with AEF. We report low short-term mortality and a cure rate of over 30% within a cohort of predominantly conservatively managed patients discussed at an MDT conference. These outcomes may reflect the benefits of individualized treatment decisions based on careful patient evaluation during MDT meetings as well as survivor bias.
Cotton domestication has fixed favorable alleles, often masking cryptic loci and reinforcing genetic trade-offs, particularly between yield and fiber quality, thereby constraining simultaneous trait improvement. We develop an eight-parent MAGIC population comprising 319 recombinant inbred lines through a 12-year breeding program and integrate it with a panel of 318 Xinjiang cotton cultivars released between 1978 and 2024. High-resolution genomic analyses combining SNP-based and identity-by-descent mapping identify 111 sQTLs and 15 hQTLs associated with 19 agronomic traits across multiple environments. Genome-wide epistasis analysis further identifies over 3,000 cryptic loci, highlighting complex genetic interactions underlying trait variation. Parallel population genomic analyses of Xinjiang cultivars reveal 520 genomic regions consistently shaped by modern breeding selection. Integrating these datasets enabled the construction of a multi-trait optimization framework to prioritize elite genotypes with favorable allele combinations. We validate this framework using cultivars derived from MAGIC parental lines, including Zhuangjiahan902 and Huaxin103, demonstrating coordinated improvement in yield and fiber quality. This study demonstrates the dual utility of MAGIC populations for high-resolution genetic dissection and breeding application. The integrative framework presented here provides a scalable strategy for resolving genetic trade-offs and achieving coordinated multi-trait improvement in cotton and other major crops.
Mutations are a continuous source of new alleles and genetic diversity in populations. Domestication and selection influence the accumulation of alleles occurring across a range of deleteriousness. Evidence suggests that mildly deleterious mutations (DelMut) can be purged out of breeding populations, increasing favorable allele accumulation. We used phylogeny-based analyses among 36 legume genomes to identify selection signatures and trained a random forest (RF) model using conservation and protein information for the prediction of DelMut in common bean populations, including a newly developed multiparent advanced generation intercrossed (MAGIC) population of black beans. Genes involved in nitrogen metabolism showed signs of positive selection in the Middle American genome, whereas genes related to phosphorylation were positively selected in the Andean genome. By combining conservation and protein information with machine learning (ML) for high-dimensional feature analysis, we characterized 82,442 sites in the MAGIC founders (36,558 polymorphic) and 4753 sites evenly sequenced among RILs that could be potentially deleterious. Variation in the number of highly DelMut (high predicted deleterious scores) among lines was observed and later correlated with agronomic traits. Phenotypic analyses showed that calculated genetic load (and number of highly DelMut) was negatively correlated with flowering time, maturity, and yield. A detailed in silico analysis of predicted mutations showed presence in highly conserved protein regions, which is likely to affect protein functionality. Our results show that variation in genetic load can be observed in breeding populations and potentially impact plant performance. These results contribute to understanding the genome-wide accumulation patterns of DelMut in breeding populations. Our study supports future development of strategies to reduce genetic load in promising germplasm and accelerate breeding programs.
Accurate reconstruction of the maxillomandibular relationship is essential for successful prosthetic rehabilitation in digital dentistry. Conventional registration techniques are severely constrained by the absence of direct overlap between the upper and lower dental arches and by their sensitivity to common clinical occlusal variations. In this paper, we introduce MAGIC-OR (Multi-dimensional Alignment with Geometric Intraoral Constraints for Occlusal Reconstruction), a framework that tightly couples multi-view intraoral scanning with geometric constraint optimization. The core of the method is a dual-buccal scanning strategy that exploits the buccal surfaces as a reliable registration bridge; an automatic selection mechanism identifies the optimal transformation among the bilateral scans, thereby coping effectively with occlusal asymmetry and unilateral data degradation. Building on this initial alignment, a geometry-constrained refinement engine with an enhanced safety metric (jointly penalizing penetration frequency, mean depth, and maximum depth) simultaneously evaluates biomechanical features-centroid distance, contact density, normal vector alignment, and gap distribution-to systematically suppress inter-arch penetration while promoting occlusal contact uniformity and stability. Comprehensive weight sensitivity analysis and ablation studies are conducted to quantify the contribution of each geometric constraint. Experiments on 155 clinical cases confirm that MAGIC-OR offers a notable advance in maxillomandibular registration, directly tackling the fundamental difficulty of limited inter-arch overlap through its geometric, dual-buccal optimization paradigm.
The Artists' Residencies in Care Homes (ARCH) programme led by Magic Me involved four arts organisations delivering participatory arts in four UK care homes for older people. The COVID-19 pandemic disrupted the programme, causing substantial trauma to care home communities. Artists paid greater attention to supporting staff and resident wellbeing and recovery from trauma. We present a trauma-informed framework for participatory arts practice in residential care homes, based on learning from the responsive approach of ARCH. The four-year programme comprised research and development focused on building relationships and testing ideas, followed by artists' residencies including workshops, performances, and training in homes, outdoor spaces, and online (e.g., Zoom, film). Artistic media included dance/movement, textiles, music, performance, film, virtual reality, and photography. The research explored how arts and care home staff collaborated to deliver and embed participatory arts in care homes. Qualitative data were collected throughout, comprising observations of meetings, training, and arts activities, alongside interviews and focus groups with artists and care home staff reflecting on their expectations, training/support needs, experiences, and learning. 11 artists, 2 Magic Me directors and 27 care home staff (including home managers, lifestyle coordinators, carers, and representatives from the care home management company) participated. Data was analysed using inductive reflexive thematic analysis. One theme captures the context and experiences of COVID-19-related trauma in care homes. Subsequent themes describe artist approaches to supporting trauma recovery in care homes: creating safe and inclusive spaces, training and support for artists/facilitators, building trusting and collaborative relationships, empowering care home staff and residents, fostering joy, and channelling the power of the participatory arts. These themes informed a trauma-informed framework for participatory arts practice in care homes. We have proposed a trauma-informed framework for participatory arts in residential care homes, which is of particular importance considering the COVID-19-related trauma that care home communities have faced. As care homes continue to recover from the emotional impacts of the pandemic, and face continuing virus outbreaks and staffing challenges, the participatory arts provide the opportunity to restore joy and promote wellbeing for care home staff and residents.
Objectives: To assess whether outcomes differ in patients with aortic graft and endograft infections (AGEIs) according to therapeutic approach (medical treatment alone versus combined medical and surgical treatment) and to describe in detail the radiological and microbiological features of these infections. Methods: This was a single-centre, observational, retrospective study including patients admitted to Monaldi Hospital, Naples, Italy, with a diagnosis of AGEI between 2005 and 2025. All patients fulfilled MAGIC criteria for definite or suspected AGEI. Results: During the study period, 37 patients were enrolled. According to MAGIC criteria, 25 patients had a definite AGEI, while 12 met criteria for suspected infection. A microbiological diagnosis was obtained in 31 patients (84%), mainly from blood cultures (68%). Medical treatment alone was chosen for 19 patients (51%), whereas 18 patients received combined medical and surgical treatment. Crude 30-day, 90-day and 1-year mortality estimates were similar between treatment groups, whereas crude 3-year mortality was numerically higher in patients receiving medical treatment alone. Kaplan-Meier analysis showed a non-significant difference in survival according to treatment strategy (log-rank p = 0.160). Conclusions: AGEIs remain a severe and often fatal complication. In this small retrospective cohort, no statistically significant survival difference was observed between treatment strategies, although a clinically meaningful benefit of surgery cannot be excluded. Graft location was associated with distinct microbiological patterns and may help guide empirical antimicrobial therapy.
Acute graft-versus-host disease (aGvHD) stands as a critical complication following haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Most existing predictive models, predominantly derived from HLA-matched donor cohorts, have been utilized for nonrelapse mortality (NRM) prediction; however, their utility in predicting aGvHD risk specifically in haplo-HSCT recipients receiving antithymocyte globulin (ATG)-based prophylaxis warrants further validation. A total of 280 patients undergoing ATG-based haplo-HSCT were retrospectively analyzed across two medical centers, split into training, internal test, and external validation cohorts. We first evaluated the predictive accuracy of the previously established Mount Sinai Acute GvHD International Consortium (MAGIC) algorithm for aGvHD, steroid-refractory aGvHD (SR-aGvHD). Subsequently, plasma concentrations of candidate cytokines (ST2, REG3α, Elafin, and TNFRI), selected a priori for their links to epithelial injury and inflammatory signaling in GvHD, were assessed for their predictive and causal relationships with aGvHD using logistic regression, weighted average area under the curve (wAUC), Mendelian randomization (MR), and restricted cubic spline (RCS) analyses. A new predictive model (the HAG model) was constructed based on identified key cytokines and validated across multicenter cohorts. MR analyses utilized external genome-wide association (GWAS) datasets to validate the reliability of identified cytokines. A visual interface for the model was created using R Shiny. MAGIC algorithm remains effective in the ATG-based haplo-HSCT setting for predicting aGvHD, achieving AUC values of 0.693 (training), 0.658 (internal test), and 0.622 (external validation). Among candidate cytokines, a combination of ST2, REG3α, and Elafin (the HAG model) demonstrated the highest predictive accuracy. MR analysis leveraging external GWAS data supported potential causal associations of ST2 (OR = 1.280, p = 0.004), REG3α (OR = 1.300, p = 0.012), and Elafin (OR = 1.209, p = 0.039) with aGvHD risk, providing complementary biological support for their selection as candidate biomarkers. The HAG model displayed good discrimination for aGvHD (AUC = 0.636-0.701) and SR-aGvHD (AUC = 0.666-0.779). Integration of clinical factors further enhanced prediction (HAG-C model, wAUC from 0.682 to 0.701). The HAG model, incorporating ST2, REG3α, and Elafin, provides clinically meaningful prediction of aGvHD and related clinical outcomes in ATG-based haplo-HSCT recipients, and may serve as a mechanistically informed tool for risk stratification and clinical management.
In large-core anterior-circulation large-vessel occlusion (LVO), differing admission clinical-imaging profiles complicate interpretation of prognostic differences between large-artery atherosclerosis (LAA) and cardioembolism (CE). We assessed whether these differences persisted after adjustment and whether endovascular thrombectomy (EVT)-outcome associations differed by etiology. We analyzed 631 patients with Alberta Stroke Program Early CT Score (ASPECTS) ≤ 5 from the 38-center MAGIC registry; 404 underwent EVT plus medical therapy and 227 received medical therapy alone. The primary outcome was 90-day modified Rankin Scale (mRS) 0-3. Mixed-effects models assessed etiology-outcome associations and treatment-by-etiology interaction. Among EVT-treated patients, Shapley decomposition quantified domain contributions to attenuation of the LAA-CE contrast. Among EVT-treated patients, higher crude odds of mRS 0-3 with LAA (OR 1.59, 95% CI 1.05-2.42) were substantially attenuated after adjustment (aOR 0.92, 95% CI 0.53-1.59). No adjusted LAA-CE contrast was evident with medical therapy alone (aOR 1.12, 95% CI 0.47-2.65). In a separate fixed-effects decomposition model, the absolute log-odds contrast was attenuated by 96.2% after inclusion of measured pretreatment domains, with imaging/collateral features, demographics, and stroke severity contributing most. For the secondary mRS 0-2 outcome, adjusted odds favored CE (aOR 0.46, 95% CI 0.25-0.84). No treatment-by-etiology interaction was detected (p = 0.944). Admission clinical-imaging phenotype clarified the apparent LAA-CE prognostic contrast and may help reconcile discordant findings across EVT cohorts. These findings reinforce established clinical-imaging criteria as the basis for hyperacute EVT selection rather than LAA versus CE etiology alone. Chinese Clinical Trial Registry (ChiCTR.org.cn); ChiCTR2100051664; https://www.chictr.org.cn/.
Liposomes have been extensively studied as carriers for delivering anticancer agents, and a formulation that encapsulates irinotecan (IRT) is currently available on the market under the name Onyvide. This study examined the molecular state of IRT within liposomes prepared with ammonium sulfate (AS) or triethylammonium sucrose octasulfate (TEA-SOS) as trapping agents using various analytical techniques. Cryogenic transmission electron microscopy revealed distinct morphologies: solid IRT precipitates in IRT/TEA-SOS liposomes, and dot-like microstructures in IRT/AS liposomes. Small-angle and wide-angle X-ray scattering (SAXS/WAXS), Raman spectroscopy, and 1H NMR analyses indicated that IRT was in a dissolved state within the inner aqueous phase of IRT/AS liposomes. In contrast, it precipitated in an amorphous form within IRT/TEA-SOS liposomes. In situ NMR measurements, conducted while varying the temperature, revealed a molecular state change of IRT during the encapsulation process. Detailed analysis of the NMR spectrum, supported by the magic-angle spinning (MAS) technique, enhanced our understanding of the molecular state, including the mobility and fraction of IRT between monomers and aggregates within the liposome. These differences in molecular states elucidated the distinct release profiles of IRT from each liposome. The solubility of IRT salts within the inner aqueous phase of the liposome played a key role in controlling the release properties of IRT. The findings highlight that the molecular state of IRT, determined by the choice of trapping agent, significantly influences release behavior and provides valuable insights for the rational design of advanced liposomal drug formulations.
Reconstruction with autologous costal cartilage remains the gold standard surgical treatment for total or partial ear reconstruction. The different auricular subunits are sculpted from costal cartilage and assembled. The assembly requires a particular skillset and training, including a thorough three-dimensional (3D) understanding of auricular anatomy. The correct positioning of the ear framework can be particularly difficult in patients with hemifacial microsomia because of facial asymmetry. We developed a digital workflow that can help the surgeon in the correct positioning of the framework via per-operative Augmented Reality (AR) and without the use of a pre-operative CT scan. The digital workflow is illustrated for two patients who underwent surgery in 2023. All patients underwent total ear reconstruction for microtia. A high-resolution digital impression was obtained from the contralateral ear using a unique scanning protocol. A Trios 3 Wireless intraoral scanner (3Shape A/S, Denmark) was used for this purpose. The remaining gaps in the STL file were closed, and the surfaces were smoothed using Meshmixer (Autodesk,US). The digital ear was mirrored and imported together with the STL model of the patients face (Vectra®, Canfield, US) in Mimics Innovation Suite (Materialise, Belgium). The digital ear was correctly positioned, and a surgical guide, including AR fiducials, was printed for peroperative use with a Magic Leap 2 (Florida, US). The digital workflow was validated using three dummy skulls. The accuracy for all measurements was within the limits of the requested margin of error for autologous ear reconstruction. The use of AR in Autologous Auricular Reconstruction was validated and appears to be feasible, precise, and useful. Challenging cases with complex facial asymmetry, such as hemifacial microsomia, will particularly benefit from this new development.