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In veterinary education, many exercises are performed on animals. Palpating the mucosa of the Ruminoreticulum in ruminants is a necessary preparatory exercise for future surgery. However, there are legal and ethical obligations to reduce the use of animals and improve animal welfare. This can be achieved using 3D models and simulators. To allow students to practice palpating the goat's forestomach, a simulator is being developed. The aim of the present study was to produce replicas of the mucosal surface of the Ruminoreticulum for the inner lining of this simulator. Two methods were applied and compared: 3D printing and surface casting. For 3D printing, computed tomography-based virtual templates were created and printed after appropriate post-processing. For the surface cast, a negative mold of the mucosal surfaces was created using epoxy resin. The positive mucosal cast was then created using silicone. The results showed a clear advantage of surface casting compared to 3D printing. The virtual templates and 3D prints lacked fine anatomical structures. In contrast, the surface casting method yielded detailed replicas of the mucosal surfaces of Rumen and Reticulum, including even finer anatomical structures. Since the silicone casts also allowed for haptic differentiation of mucosal formations, they can be considered a suitable inner lining for the planned simulator.

Cold cases involving fragmented skeletal remains present major interpretative challenges, particularly when craniofacial trauma must be reconstructed from fragile, scattered bone fragments. In the present case, human remains discovered during excavation were severely altered and exhibited multiple craniofacial fractures. Forensic anthropologists and maxillofacial surgeons collaborated to restore cranial volume and clarify injury mechanism using a hospital-based digital workflow. All fragments were scanned using cone-beam computed tomography, manually segmented, virtually reassembled based on cortical congruence and anatomical landmarks, and reproduced at full scale via fused deposition modeling. Three-dimensional reconstruction revealed clustered radial and concentric craniofacial fractures consistent with multiple blunt impacts. Physical replicas enabled manual reassembly while minimizing manipulation of the original remains. Both the virtual reconstruction and the assembled printed skull were subsequently presented to the investigating magistrate. This technical note highlights the potential of maxillofacial digital workflows to support non-destructive reconstruction of complex craniofacial trauma in forensic contexts.

This study compared the quality and efficiency&#xa0;of three obturation techniques for simulated 3D-printed C-shaped canals filled with an epoxy resin-based sealer.&#xa0;A mandibular molar with a C-shaped root canal (C1 configuration) was prepared to size #30/0.04, and 30 replicas were 3D-printed. The canals were obturated with AH Plus Jet sealer using cold lateral compaction (CLC), warm vertical compaction (WVC), or warm vertical hybrid compaction (HC) (n&#x2009;=&#x2009;10). Cross-sections at the apical, middle, and coronal thirds were examined under a digital microscope to determine the proportions of gutta-percha, sealer, and voids. Obturation time was also recorded. Data were analyzed with one-way ANOVA and LSD post-hoc tests (&#x3b1;&#x2009;=&#x2009;0.05). In the apical third, void percentages were significantly lower for CLC (1.00&#xb1;0.21%) and HC (1.00&#xb1;0.43%) compared with WVC (P<0.001), although the effect size indicated only a modest difference (&#x3b7;2&#x2009;=&#x2009;0.218). In the middle third, WVC produced the lowest void percentage (1.03&#x2009;&#xb1;&#x2009;0.37%; P&#x2009;<&#x2009;0.05). In the coronal third, void percentages in WVC and HC were significantly lower than in CLC (P&#x2009;<&#x2009;0.05). Among the techniques, WVC required the shortest obturation time (168.00&#x2009;&#xb1;&#x2009;24.29 s; P&#x2009;<&#x2009;0.001).&#xa0;Considering void percentage and treatment time, WVC appears to be the most efficient technique for obturating C-shaped canals with AH Plus Jet sealer.

Deep-derived carbon dioxide (CO2) degassing is a globally important process linking crust-mantle fluid transport with atmospheric carbon budgets. Matched Field Processing-Bartlett Beamformer (MFP-BB) method offers a seismic approach for detecting tremor signals generated by these degassing centers (mofette). Its principle relies on comparing recorded wavefields with modeled replicas to identify the most likely source locations. This study applies the MFP-BB technique to dense-array seismic noise data from three key mofette areas in the Cheb Basin, western Eger Rift-Bubl&#xe1;k, Hartou&#x161;ov, and Soos. We combine field observations with numerical simulations to evaluate the method's performance. Synthetic tests with interfering noise-embedded sources (SNR&#x2009;=&#x2009;5 dB) demonstrate that accurate localization is achievable with appropriate frequency selection, and that even 20% perturbations in the velocity model introduce only minor degradation. Field data were processed through segmentation, noise filtering, and spectral analysis to determine persistent frequency bands used in the algorithm. Across all sites, MFP-BB energy concentrates near the surface, coinciding with known mofette fields and CO2 discharge zones. These shallow anomalies reflect microtremors generated as ascending CO2 interacts with groundwater and unconsolidated sediments; additional, weaker anomalies at depths&#x2009;<&#x2009;200&#xa0;m may also represent active gas migration.

Accurate and standardized phenotyping of complex, environmentally sensitive quantitative traits remains a major bottleneck for reliable locus discovery and breeding applications. Here, we established a skeleton-guided 3D digital phenotyping framework that generates standardized digital replicas and enables precise quantification of fruit and plant architecture traits in cucumber. The workflow was applied to a permanent recombinant inbred line (RIL) population (n&#x2009;=&#x2009;211) evaluated across two seasons (2023-2024), from which nine traits were extracted from 3D models. All 211 RILs were whole-genome resequenced to generate genome-wide SNPs, enabling construction of a high-density linkage map and subsequent QTL mapping, complemented by GWAS for physical anchoring of association signals. Using this integrated design, we identified 29 QTLs across the nine traits and resolved cross-season major-effect loci with consistent genetic signals. Notably, two cross-season loci were detected as novel: FL4.1/FSL4.1 affecting fruit length and fruit stalk length, and NLB1.1/LLB1.1 affecting branching. GWAS further anchored lead variants to physical coordinates and supported cross-season associations. Together, these results demonstrate that standardized 3D phenotyping provides a reproducible and interoperable trait definition framework that supports cross-season locus discovery and downstream marker development for quantitative genetic dissection in cucumber.

Digital Twin (DT) technology is redefining healthcare through dynamic, data-driven virtual replicas of patients, medical devices, and complex clinical systems that continuously learn and evolve. By integrating real-time physiological data, advanced imaging, multi-omics, and comprehensive clinical records, DTs enable sophisticated simulation, prediction, and optimization across the care continuum. This paper examines how DTs accelerate the transition toward precision medicine, predictive analytics, and value-based healthcare delivery. It explores emerging applications in clinical decision support, advanced surgical planning, hospital operations, and drug development through in silico trials. As the European Health Data Space (EHDS) enters its implementation phase in 2026, establishing secure, validated, and ethically governed DT frameworks is crucial to achieving personalized, preventive, and participatory healthcare across Europe.

Clinical trials in IBD face difficulties of escalating complexity, high costs and challenges in recruitment. Digital twins are virtual, data-driven replicas of individual patients that model disease trajectories and treatment responses, which offer a potential innovative change in the conduct of clinical trials in IBD. Built from multimodal datasets integrating clinical, molecular, imaging and real-world data, digital twins can generate synthetic control arms, enable adaptive randomisation and predict disease relapse or treatment response. Early studies across oncology, cardiology and endocrinology demonstrate their feasibility and potential to improve statistical power while reducing patient burden. However, the integration of digital twins into clinical trials in IBD will require rigorous validation frameworks, transparent data governance and attention to algorithmic bias and consent. In this review, we explore how digital twins may transform IBD research-from in silico simulation to adaptive, patient-centred trial design-and outline the regulatory, ethical and logistical challenges to be considered in order to successfully integrate them into future trials.

This in vitro study compared the precision of articulator-based scanning and scan fixator-based scanning in completely edentulous arches with implant scan bodies. Upper and lower master casts were fabricated from a typodont, and six implant replicas were placed in each arch. Final impressions were used to fabricate master casts, which were subsequently mounted on an Artex articulator. Implant scan bodies were attached during the digital scanning procedures. Two scanning protocols were evaluated: (1) casts mounted on an Artex articulator and (2) casts mounted using a scan fixator. Each configuration was scanned ten times using an extraoral desktop scanner, and all scans were exported as STL files. Precision was evaluated using CloudCompare software by performing pairwise superimpositions within each group. Root mean square (RMS) values were calculated from all pairwise comparisons to assess intra-group variability. A total of 45 pairwise comparisons per group were analyzed. RMS values showed high variability and right-skewed distributions. The scan fixator showed a mean RMS of 106.6&#x2009;&#xb1;&#x2009;206.8&#xa0;&#x3bc;m (median 17.9&#xa0;&#x3bc;m), while the articulator showed 178.9&#x2009;&#xb1;&#x2009;276.5&#xa0;&#x3bc;m (median 22.2&#xa0;&#x3bc;m). No significant difference was found between groups using the Wilcoxon signed-rank test (p&#x2009;=&#x2009;.446) or the paired t-test on log-transformed data (p&#x2009;=&#x2009;.334). After excluding 20 outlier pairs, results remained unchanged (p&#x2009;>&#x2009;.4 for both tests). Overall, both systems demonstrated comparable precision with no statistically significant differences in RMS values. There was no statistically significant difference in precision between articulator-based scanning and scan fixator-based scanning in edentulous arches with implant scan bodies. The scan fixator may represent a cost-effective and clinically acceptable alternative in digital implant workflows.

Molecules exposed to intense femtosecond laser fields display a complex interplay of multiphoton ionization, resonances, and tunneling dynamics. Although above-threshold ionization (ATI) has been extensively characterized in atoms, its resonance-enhanced counterpart in polyatomic molecules has remained elusive. Here we investigate the strong-field ionization of ammonia (NH3) by 800 nm femtosecond pulses coupled with photoelectron velocity map imaging, exploiting its distinctive vibrational fingerprint in the umbrella bending mode. We uncover a weak Stark-induced Freeman resonance whose ATI replicas are shown to dominate over the parent channel. A strong resonance-enhanced above-threshold ionization (REATI) phenomenon is thus demonstrated here in a polyatomic molecule. Moreover, our results connect non-resonant and resonant multiphoton ionization, Freeman resonances, ATI, and REATI, into a unified roadmap, establishing ammonia as a benchmark system for exploring vibrationally resolved strong-field ionization. Beyond unveiling a distinct regime of molecular ionization, our findings highlight how the vibrational structure governs strong-field phenomena in complex molecules.

The interaction of large, membrane-bound vesicles leads to the development of extended diaphragms that act as intermediates in the fusion process. Such hemifusion diaphragms confined inside a stiffer container may disassemble through energetically distinct rim-pore expansion modes (radial or lateral), and the preferred mode depends on diaphragm size and lipid reabsorption costs. We propose a theoretical model based on constrained-wetting physics to explain why large hemifusion diaphragms favor lateral rim-pore propagation while small hemifusion diaphragms prefer radial growth. We combine coarse-grained unbiased molecular dynamics of confined vesicle-in-vesicle systems in the &#x3bc;s-scale, with an analytical geometrical model derived from interface wetting. Energies include line tensions for membrane building blocks (edges, arcs and Y-junctions), diaphragm lateral tension, and a lipid reabsorption term accounting for area transfer and flip-flop controlled stress-asymmetry. Simulation observables (rim-pore area, arc/edge/Y-junction lengths and contact angles) are directly compared to model predictions. The wetting-inspired energy model predicts two regimes. For large hemifusion diaphragms lateral propagation minimizes both edge length and reabsorption costs and therefore is energetically preferred, producing rapid lateral expansion and micelle formation via a final fission. For small hemifusion diaphragms radial propagation is favored, producing slow bleb reabsorption without fragment excision. Independent unbiased trajectory replicas (n=10 per regime) reproduce these predictions quantitatively (rim-pore area, contact angles, expansion timescales). Results unify geometric and wetting analogies with numerical simulation evidence, and reveal a mechanistic pathway for selective fast or slow hemifusion diaphragm disassembly with implications for controlled membrane self-reorganization under spatial confinement.

Computational approaches, particularly molecular dynamics (MD) simulations, offer powerful tools for studying the membrane binding of peripheral membrane proteins (PMPs) and their interactions with lipids. However, the simulation of membranes at an atomic level is constrained by timescale limitations, further compounded by the slow diffusion of lipids in the membrane. The highly mobile membrane mimetic (HMMM) model was developed as one of the alternative membrane representations to overcome some of these limitations, particularly for investigating membrane binding of PMPs. By using short-tailed lipids, the HMMM model significantly enhances the lateral diffusion of lipids, thereby substantially accelerating membrane-associated phenomena. In this chapter, we outline best practices for setting up protein-HMMM systems and provide examples of relevant analyses. Ideally, one begins by thoroughly researching and understanding the protein of interest, including its cellular localization, the type of membrane it interacts with, and any biochemical evidence for structural changes upon membrane binding. Additional considerations include the quality of the available structures, as well as relevant posttranslational modifications, and involvement of ligands or cofactors. After constructing and equilibrating a representative full-length (FL) membrane with the desired lipid composition, it can be converted into an HMMM representation by using an in-house script provided in the SI materials or resources such as CHARMM-GUI. The PMP is then positioned on top of the HMMM membrane at a long enough distance from it and in different orientations to avoid biasing the membrane-binding process across multiple replicas with shuffled lipid arrangements. Following a careful equilibration protocol, one can capture spontaneous membrane-binding events for PMPs during production MD simulations. To quantify the membrane-binding events, one would first identify stable membrane-bound segments of the HMMM trajectories, which can be done by monitoring protein-membrane contacts. Analyzing these membrane-bound frames can then provide insights into membrane interaction hotspots, potential membrane-anchoring residues, the protein's selectivity for particular lipid types, and distinct membrane-bound poses that may be relevant to function or activation. Finally, it is crucial to verify the results from HMMM simulations by analyzing the findings after converting the protein-membrane system back to FL membranes, which can be done using an in-house script provided in the SI materials, and conducting additional simulations.

Digital twin technology represents a transformative approach in healthcare, creating virtual replicas of physical entities that enable real-time data integration, predictive modelling, and personalised treatment strategies. In urology, this emerging technology offers unprecedented opportunities to optimise patient care through simulation-based decision-making. This narrative review comprehensively examines current applications of digital twin technology in urology, evaluates its clinical utility across various urological conditions, and identifies key challenges limiting its widespread implementation. A comprehensive search was conducted across PubMed, Web of Science, and Scopus databases for literature published between January 2020 and January 2026. Search terms included digital twin, virtual twin, urology, uro-oncology, prostate cancer, renal surgery, and bladder dysfunction. Studies focusing on the development, validation, and clinical implementation of digital twins in urological practice were included. Digital twin technology demonstrates significant potential in uro-oncology for treatment planning, surgical navigation, and disease progression monitoring. Key applications include patient-specific tumour growth simulation in prostate cancer, three-dimensional anatomical modelling for partial nephrectomy, and bladder function prediction in outlet obstruction. Integration with artificial intelligence enhances predictive accuracy and enables real-time surgical guidance. Digital twin technology represents a paradigm shift towards precision urology, though challenges in data integration, computational requirements, validation, and ethical considerations must be addressed before routine clinical implementation. Future developments should focus on standardisation, regulatory frameworks, and prospective clinical validation studies.

A recipe for producing carbon extraction replicas from twin-jet electropolished disks is described. This technique allows tracking the analysed region with respect to the bulk sample. An example use of the method as applied to a reduced activation ferritic martensitic (RAFM) steel, 'UK-RAFM', is reported. The RAFM steel described originates from a &#x223c;5 tonne heat produced via electric-arc furnace (EAF) and was intended to match Eurofer-97 in chemistry. Here, a detailed analysis of the precipitates within the UK-RAFM is provided, with particular emphasis to show the variability in chemistry of second-phase precipitates (SPPs). Comparisons to literature reported compositions of Eurofer-97 SPPs indicate they are in reasonable agreement; comparisons are also made against thermodynamic models.

The aim of this clinical trial was to evaluate and compare the 12-month performance of a contemporary injectable and a conventional paste-type resin composite in Class I cavities using the modified USPHS criteria, supported by SEM analysis. A total of 72 teeth from 34 volunteers were included. Each participant received at least two restorations (one per material); in cases where more eligible cavities were present, additional restorations were performed accordingly. All restorations were performed under rubber dam isolation following conservative Class I cavity preparation, using selective enamel etching and a universal adhesive. All procedures were carried out by the same clinician using a paste-type resin composite (Filtek Z250 Universal Restorative) and an injectable resin composite (G-&#xe6;nial Universal Injectable). Two calibrated investigators evaluated restorations at baseline, 6, and 12 months using modified USPHS criteria. SEM analysis was conducted on a total of 66 epoxy replicas obtained at baseline, 6, and 12 months from 11 randomly selected participants. Statistical analysis was performed using SPSS (Version 23.0, IBM, NY) with Pearson's chi-square and Cochran's Q tests. Both materials demonstrated comparable and clinically acceptable performance over the 12-month evaluation period according to the modified USPHS criteria, with no statistically significant differences observed at any time point across all criteria, although minor changes were observed in marginal adaptation and color match in a few restorations (p&#x2009;>&#x2009;0.05). All participants attended the follow-up visits, resulting in a 100% recall and retention rate. The injectable (G-&#xe6;nial Universal Injectable) and paste-type (Filtek Z250) resin-composites demonstrated comparable and clinically acceptable short-term performance in Class I occlusal restorations, although longer-term follow-up is needed to confirm these findings. As trial registration took place after the first participant was enrolled, the study was retrospectively registered at ClinicalTrials.gov on December 21, 2023, with ID: NCT06192667. https://register. gov/prs/beta/studies/S000DTX600000072/recordSummary /.

Sufficient ventilation during cardiopulmonary resuscitation (CPR) is increasingly recognised as a critical determinant of patient outcomes. The effectiveness of ventilation training, however, likely depends on the anatomical and mechanical fidelity of CPR manikins. While chest compression mechanics of manikins have been studied extensively, ventilation-related anatomy, airflow pathways, and respiratory mechanics have not been evaluated systematically. This study analysed 10 adult CPR manikins from three manufacturers. Airway and lung replicas were documented using photography, video laryngoscopy, and bronchoscopy. Expiratory tidal volume and air leakage were measured during volume-controlled mechanical ventilation via facemask, supraglottic airway devices and endotracheal tube. Mechanics of the respiratory system were described by the peak and plateau airway pressures and respiratory compliance. Manikins differed substantially in airway design and expiratory airflow design. Three distinct expiratory mechanisms were identified, of which only one permitted exhalation through the airway and thus quantification of expiratory tidal volumes. Air leakage varied across manikins and airway devices, including during ventilation via advanced airway devices. Respiratory mechanics showed marked variability, with peak inspiratory pressures ranging from 21&#xa0;&#xb1;&#xa0;1 to 56&#xa0;&#xb1;&#xa0;1&#xa0;mbar and compliances from 7&#xa0;&#xb1;&#xa0;0 to 51&#xa0;&#xb1;&#xa0;4&#xa0;mL/mbar. Several models exhibited substantial leakage via the gastric channel of the i-gel&#xae; supraglottic airway. CPR manikins exhibited substantial variability in ventilation-related anatomy, airflow pathways, leakage and respiratory mechanics. None of the assessed manikins consistently approximated human ventilation characteristics across airway devices, underscoring the need for local evaluation of manikin-airway device combinations to optimise ventilation fidelity in CPR training.

Glucagon-like peptide-1 receptor (GLP-1R) agonists show substantial inter-individual variability in efficacy, but the structural basis by which common GLP-1R variants alter receptor behavior remains unclear. We examined the GLP-1R R131Q variant using all-atom molecular dynamics simulations across four conditions (wild type [WT] and R131Q in ligand-free and GLP-1-bound states; 8-11 replicas per condition; 600 ns each) together with isogenic human induced pluripotent stem cell (iPSC)-derived pancreatic models. In ligand-free simulations, principal component analysis identified a variant-enriched subensemble associated with coordinated deviations spanning TM1 and the ECL3-side region. Residue-131-centered analysis showed weakening of WT-like local anchoring and a variant-specific increase in Q131-R376 close occupancy from near zero in WT to 0.101. In bound simulations, the ligand-free-specific Q131-R376 signature was lost. Instead, the variant weakened the residue-131-E128 local anchor and redistributed receptor-peptide interface and deep-pocket contact states, consistent with upper-receptor repacking. MM/GBSA analysis showed weaker estimated overall GLP-1 binding energetics in R131Q together with redistribution of energetic contributions within the bound receptor-peptide interface. In iPSC-derived pancreatic &#x3b2;-like cells and exendin-4-stimulated endocrine progenitors, R131Q was associated with increased &#x3b2;-cell maturity markers and enhanced mitochondrial, antioxidant, and stress-response readouts, including increased IDH2/MDH1 expression and enhanced mitochondrial staining. Together, these findings support a state-dependent model in which R131Q rewires local and distal GLP-1R conformational ensembles, with associated mitochondrial and stress-response phenotypes in human pancreatic models.

The objective of this study was to describe a novel method of femoral torsion correction in dogs and partially validate the technique by applying it to femoral bone models. We conducted an in vitro study using 12 femoral bone models. Twelve bone models, consisting of 6 replicas of each of 2 right femurs (Bone Model 1 and Bone Model 2), were reconstructed, using stereolithography, from femoral computed tomographic scans of 2 chondrodystrophic dogs. An intramedullary pin-assisted distal femoral osteotomy (IPA-DFO) was done on all bone models to correct 30&#xb0; of torsion (CTA2). Preoperative and postoperative femoral anteversion angle (FAA) and anatomical lateral distal femoral angle (aLDFA) were measured. The magnitude of torsional correction was defined as the T angle, calculated as the difference between postoperative and preoperative FAA. Mean T angle was 31.7 &#xb1; 1.7&#xb0; for Bone Model 1 and 30.8 &#xb1; 0.9&#xb0; for Bone Model 2. No significant differences were detected between CTA2 and T angles in either bone model. No significant differences were observed between preoperative and postoperative aLDFA values. The IPA-DFO consistently reproduced the planned femoral torsion correction in the bone models studied without inducing unintended frontal plane alignment change. Description d&#x2019;une nouvelle m&#xe9;thode de correction de la torsion f&#xe9;morale chez les chiens : &#xe9;tude in vitro. L&#x2019;objectif de cette &#xe9;tude &#xe9;tait de d&#xe9;crire une nouvelle m&#xe9;thode de correction de la torsion f&#xe9;morale chez les chiens et de valider partiellement la technique en l&#x2019;appliquant &#xe0; des mod&#xe8;les osseux f&#xe9;moraux. Nous avons men&#xe9; une &#xe9;tude in vitro &#xe0; l&#x2019;aide de 12 mod&#xe8;les osseux f&#xe9;moraux. Ces 12 mod&#xe8;les, compos&#xe9;s de 6 r&#xe9;pliques de chacun de 2 f&#xe9;murs droits (Mod&#xe8;le osseux 1 et Mod&#xe8;le osseux 2), ont &#xe9;t&#xe9; reconstruits par st&#xe9;r&#xe9;olithographie &#xe0; partir de tomodensitom&#xe9;tries f&#xe9;morales de 2 chiens chondrodystrophiques. Une ost&#xe9;otomie f&#xe9;morale distale assist&#xe9;e par tige intram&#xe9;dullaire (OFD-TI) a &#xe9;t&#xe9; r&#xe9;alis&#xe9;e sur tous les mod&#xe8;les osseux afin de corriger une torsion de 30&#xb0; (CTA2). L&#x2019;angle d&#x2019;ant&#xe9;version f&#xe9;morale (AAF) et l&#x2019;angle f&#xe9;moral distal lat&#xe9;ral anatomique (AFDLa) ont &#xe9;t&#xe9; mesur&#xe9;s en pr&#xe9;- et postop&#xe9;ratoire. L&#x2019;amplitude de la correction de la torsion a &#xe9;t&#xe9; d&#xe9;finie comme l&#x2019;angle T, calcul&#xe9; comme la diff&#xe9;rence entre l&#x2019;AAF postop&#xe9;ratoire et pr&#xe9;op&#xe9;ratoire. L&#x2019;angle T moyen &#xe9;tait de 31,7 &#xb1; 1,7&#xb0; pour le Mod&#xe8;le osseux 1 et de 30,8 &#xb1; 0,9&#xb0; pour le Mod&#xe8;le osseux 2. Aucune diff&#xe9;rence significative n&#x2019;a &#xe9;t&#xe9; observ&#xe9;e entre les angles CTA2 et T dans les deux mod&#xe8;les osseux. Aucune diff&#xe9;rence significative n&#x2019;a &#xe9;t&#xe9; observ&#xe9;e entre les valeurs AFDLa pr&#xe9;op&#xe9;ratoires et postop&#xe9;ratoires. L&#x2019;OFD-TI a permis de reproduire de mani&#xe8;re constante la correction de torsion f&#xe9;morale planifi&#xe9;e dans les mod&#xe8;les osseux &#xe9;tudi&#xe9;s, sans induire de modification non intentionnelle de l&#x2019;alignement dans le plan frontal.(Traduit par Dr Serge Messier).

Biologically functional RNAs operate near marginal stability, and their rugged free-energy landscapes and profound structural dynamics - typically not captured by structural biology experiments - play decisive roles. Atomistic molecular dynamics (MD) simulations provide a unique means to characterize these features. However, the applicability of atomistic MD is currently limited by accessible simulation time scales and, most importantly, by force-field (FF) accuracy. Folding free energies (&#x394;G&#xb0;fold) of small RNA motifs represent well-defined targets for quantitative benchmarking of RNA FFs. In practice, however, obtaining thermodynamic estimates that are sufficiently robust for direct comparison with experimental data remains highly challenging, even for small RNA systems, and many published studies rely on sampling that is not fully converged. Here, we systematically assess the performance of widely used advanced enhanced sampling techniques using the 8-mer r(gcGAGAgc) tetraloop as a representative benchmark system. We test temperature replica exchange (T-REMD), two solute-tempering variants of replica exchange (REST2 and REHT), as well as well-tempered metadynamics and on-the-fly probability enhanced sampling combined with solute tempering (ST-MetaD and ST-OPES). Among the tested approaches, T-REMD proves to be the most robust, yielding reproducible folding equilibria and consistent estimates of &#x394;G&#xb0;fold after approximately 20 &#x3bc;s of simulation time, independent of the initial folded or unfolded conformational ensemble. Our results provide practical guidelines for selecting sampling protocols suitable for quantitative RNA benchmarks and lay the foundation for systematic validation and future refinement of RNA FFs.

Variables related to CAD/CAM processing can affect the final quality of all-ceramic crowns. This study aims to evaluate the effect of the milling protocol on the adaptation, marginal and occlusal quality of monolithic zirconia crowns. Thirty-nine monolithic zirconia crowns were produced using three CAD/CAM milling protocols (n&#x2009;=&#x2009;13): slow (S), normal (N), and fast (F). Adaptation (gap thickness) was evaluated using the replica technique, while marginal quality was assessed according to a severity scale. Occlusal quality was investigated qualitatively, using a stereomicroscope, and quantitatively, through an occlusal dimensional discrepancy analysis. Gap thickness and occlusal discrepancy data were analyzed with ANOVA and Tukey's test, and marginal quality with Kruskal-Wallis and Student-Newman-Keuls (&#x3b1;&#x2009;=&#x2009;0.05). Gap thickness in the marginal, gingival-axial angle and axial regions was similar among groups. In the axio-occlusal angle and occlusal region, group N presented the smallest gap. For marginal quality, group F had higher scores in the severity scale than groups N and S for the mesial and buccal regions. Group F crowns showed less refined occlusal anatomy. Yet, when crowns produced with S and F protocols were compared with N, the total mean discrepancy was similar. The CAD/CAM milling protocol affected the adaptation, marginal, and occlusal quality of monolithic zirconia crowns.