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Abstract Cardiac digital twins provide a physics and physiology informed framework to deliver personalized medicine. However, high-fidelity multi-scale cardiac models remain a barrier to adoption due to their extensive computational costs. Artificial Intelligence-based methods can make the creation of fast and accurate whole-heart digital twins feasible. We use Latent Neural Ordinary Differential Equations (LNODEs) to learn the pressure-volume dynamics of a heart failure patient. Our surrogate model is trained from 400 simulations while accounting for 43 parameters describing cell-to-organ cardiac electromechanics and cardiovascular hemodynamics. LNODEs provide a compact representation of the 3D-0D model in a latent space by means of an Artificial Neural Network that retains only 3 hidden layers with 13 neurons per layer and allows for numerical simulations of cardiac function on a single processor. We employ LNODEs to perform global sensitivity analysis and parameter estimation with uncertainty quantification in 3 hours of computations, still on a single processor.

Abstract Predicting the evolution of systems with spatio-temporal dynamics in response to external stimuli is essential for scientific progress. Traditional equations-based approaches leverage first principles through the numerical approximation of differential equations, thus demanding extensive computational resources. In contrast, data-driven approaches leverage deep learning algorithms to describe system evolution in low-dimensional spaces. We introduce an architecture, termed Latent Dynamics Network, capable of uncovering low-dimensional intrinsic dynamics in potentially non-Markovian systems. Latent Dynamics Networks automatically discover a low-dimensional manifold while learning the system dynamics, eliminating the need for training an auto-encoder and avoiding operations in the high-dimensional space. They predict the evolution, even in time-extrapolation scenarios, of space-dependent fields without relying on predetermined grids, thus enabling weight-sharing across query-points. Lightweight and easy-to-train, Latent Dynamics Networks demonstrate superior accuracy (normalized error 5 times smaller) in highly-nonlinear problems with significantly fewer trainable parameters (more than 10 times fewer) compared to state-of-the-art methods.

Abstract Background Simulating the cardiac function requires the numerical solution of multi-physics and multi-scale mathematical models. This underscores the need for streamlined, accurate, and high-performance computational tools. Despite the dedicated endeavors of various research teams, comprehensive and user-friendly software programs for cardiac simulations, capable of accurately replicating both normal and pathological conditions, are still in the process of achieving full maturity within the scientific community. Results This work introduces $$\texttt {life}^{\text{x}}$$ life x -ep, a publicly available software for numerical simulations of the electrophysiology activity of the cardiac muscle, under both normal and pathological conditions. $$\texttt {life}^{\text{x}}$$ life x -ep employs the monodomain equation to model the heart’s electrical activity. It incorporates both phenomenological and second-generation ionic models. These models are discretized using the Finite Element method on tetrahedral or hexahedral meshes. Additionally, $$\texttt {life}^{\text{x}}$$ life x -ep integrates the generation of myocardial fibers based on Laplace–Dirichlet Rule-Based Methods, previously released in Africa et al., 2023, within $$\texttt {life}^{\text{x}}$$ life x -fiber. As an alternative, users can also choose to import myofibers from a file. This paper provides a concise overview of the mathematical models and numerical methods underlying $$\texttt {life}^{\text{x}}$$ life x -ep, along with comprehensive implementation details and instructions for users. $$\texttt {life}^{\text{x}}$$ life x -ep features exceptional parallel speedup, scaling efficiently when using up to thousands of cores, and its implementation has been verified against an established benchmark problem for computational electrophysiology. We showcase the key features of $$\texttt {life}^{\text{x}}$$ life x -ep through various idealized and realistic simulations conducted in both normal and pathological scenarios. Furthermore, the software offers a user-friendly and flexible interface, simplifying the setup of simulations using self-documenting parameter files. Conclusions $$\texttt {life}^{\text{x}}$$ life x -ep provides easy access to cardiac electrophysiology simulations for a wide user community. It offers a computational tool that integrates models and accurate methods for simulating cardiac electrophysiology within a high-performance framework, while maintaining a user-friendly interface. $$\texttt {life}^{\text{x}}$$ life x -ep represents a valuable tool for conducting in silico patient-specific simulations.

Atrial fibrillation (AF) patients are at high risk of stroke, with the left atrial appendage (LAA) found to be the most common site of clot formation. Presence of left atrial (LA) fibrosis has also been associated with higher stroke risk. However, the mechanisms for increased stroke risk in patients with atrial fibrotic remodeling are poorly understood. We sought to explore these mechanisms using fluid dynamic analysis and to test the hypothesis that the presence of LA fibrosis leads to aberrant hemodynamics in the LA, contributing to increased stroke risk in AF patients. We retrospectively collected late-gadolinium-enhanced MRI (LGE-MRI) images of eight AF patients (four persistent and four paroxysmal) and reconstructed their 3D LA surfaces. Personalized computational fluid dynamic simulations were performed, and hemodynamics at the LA wall were quantified by wall shear stress (WSS, friction of blood), oscillatory shear index (OSI, temporal directional change of WSS), endothelial cell activation potential (ECAP, ratio of OSI and WSS), and relative residence time (RRT, residence time of blood near the LA wall). For each case, these hemodynamic metrics were compared between fibrotic and non-fibrotic portions of the wall. Our results showed that WSS was lower, and OSI, ECAP, and RRT was higher in the fibrotic region as compared to the non-fibrotic region, with ECAP (p = 0.001) and RRT (p = 0.002) having significant differences. Case-wise analysis showed that these differences in hemodynamics were statistically significant for seven cases. Furthermore, patients with higher fibrotic burden were exposed to larger regions of high ECAP, which represents regions of low WSS and high OSI. Consistently, high ECAP in the vicinity of the fibrotic wall suggest that local blood flow was slow and oscillating that represents aberrant hemodynamic conditions, thus enabling prothrombotic conditions for circulating blood. AF patients with high LA fibrotic burden had more prothrombotic regions, providing more sites for potential clot formation, thus increasing their risk of stroke.

The COVID-19 epidemic has changed patients’ approach to dental treatments. While dentists worldwide have shown an excellent level of adaptability to face the new challenges presented by the unprecedented situation due to the rapid spread of COVID-19, dental patients have witnessed a sudden suspension of elective treatments and a slow resumption of dental care activities after several national lockdowns. In addition, the general climate of anxiety and fear due to the high COVID-19 risk and the high level of mortality has influenced the perception and attitudes of people towards dental activity, inducing many dental patients to avoid appointments to the dentist if not highly urgent. We present an overview of the current state of knowledge about dental patients’ perception, perspective, attitude, and expectations towards a full resumption of regular dental treatments.

BackgroundEx vivo and in vitro studies have demonstrated the effectiveness of some irrigation protocols in reducing the bacterial load in the root canal system. However, standardized protocols have not yet been defined for the real clinical context due to many irrigation procedures available.ObjectiveTo evaluate the clinical endodontic protocols and limitations of irrigating solutions in the disinfection of the root canal system in patients with apical periodontitis.MethodsPubMed, Scopus, Embase, Web of Science, and Cochrane databases were searched for randomized controlled trials (RCT) published until January 2021. Hand searching was also performed. Studies focused on evaluating the effectiveness of irrigating solutions and/or irrigation activation methods in reducing the bacterial load in the root canal system were considered. The Cochrane risk-of-bias tool for randomized trials (RoB2) was used to assess the quality of the studies.ResultsFour hundred and twenty eight published articles were identified. After removing the duplicate studies and analyzing full texts, seven RCTs were selected. Two studies compared pure NaOCl with some combination of NaOCl with HEDP and MTAD. Two studies analyzed the antibacterial efficacy of NaOCl and chlorhexidine (CHX). Three studies compared conventional needle irrigation with different irrigation activation methods (PUI, XP-endo finisher, F-file activator, EndoVac activator). The review attained a satisfactory methodology. The main results of each included study were described.DiscussionActivation methods provide significantly higher biofilm reduction than conventional needle irrigation methods. Combinations of NaOCl with different chelating agents were ineffective in terms of antimicrobial, but it could potentially increase the risk of irrigant extrusion. However, the irrigating protocols were not carefully detailed, especially those regarding the irrigants application time or total volume. The existing literature lacks high-quality studies. The level of evidence is moderate.ConclusionsThe available data is too heterogeneous to compare and identify the superiority of specific valuable irrigation protocols in each clinical context. Application time, volume, and activation methods should be standardized to determine the optimal irrigating procedures to reduce the bacterial load and ensure higher predictability of the endodontic treatment.Systematic Review Registration(https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=218555), PROSPERO registration: CRD42020218555.

(1) Background: To improve endodontic treatments, it is necessary to find good irrigant solutions that balance potential toxic effects with optimal antimicrobial capacity. The aim of this laboratory study was to assess the cytotoxic and antimicrobial capacity of phytic acid (IP6) and BioAktTM in a laboratory setting to determine their suitability prior to endodontic evaluation. (2) Methods: The antimicrobial and cytotoxic effects of IP6 and BioAktTM were compared with those of 1.5% NaOCl. Cytotoxicity was evaluated via crystal violet assay and CellTiter-Glo® 2.0 assay, while antimicrobial capacity was tested via disk diffusion and the effect of a 1-h treatment on Enterococcus faecalis. (3) Results: A crystal violet test and CellTiter-Glo® 2.0 assay showed statistically significant differences in cell viability and cell activity after 4 and 24 h for all tested solutions (p < 0.05). The antimicrobial activity of BioAktTM was similar to that of 1.5% NaOCl, while phytic acid showed the lowest antimicrobial activity compared to BioAktTM (p < 0.05) and 1.5% NaOCl (p < 0.05). (4) Conclusion: BioAktTM showed an optimal balance between antimicrobial activity and cytotoxicity.

(1) Background: In endodontics, anatomical complexities and irregularities in the root canal system may interfere with sealer penetration, increasing the risk of treatment failure. This work aimed to investigate the effects of sonicated Thermafil (Dentsply, Tulsa Dental Specialties, Johnson City, TN, USA) on sealer penetration into the dentinal tubules. (2) Methods: Thirty teeth with single round-shaped root canals were used to compare Sonicated Thermafil with sonication (ST—10 teeth), System B (EIE Analytical Technology, Orange, CE, USA) (SB—10 teeth), and Thermafil without sonication (T—10 teeth). A confocal laser scanning microscope (CLSM) was used to determine the depth, area, and percentage of sealer penetration into the dentinal tubules. (3) Results: ST showed the deepest average penetration at 6 mm from the apex compared to SB (p < 0.01) and T (p < 0.01) and at 3 mm compared to SB (p < 0.01). In addition, it had the highest penetration values at both levels compared to SB (p < 0.01) and T (p < 0.05) and a higher penetration area at 6 mm compared to T (p < 0.05) and SB (p < 0.05). (4) Conclusion: Sonic activation can improve the carrier-based obturation technique thanks to deeper sealer penetration and thus better retention of materials.

Hypochlorite accidents are relatively rare events. Therefore, there is a lack of precise and accurate reports in the scientific literature that could help clinicians better understand the phenomenon and associated risk factors. This study reported four hypochlorite accidents attributable to 5% NaOCl extrusion in patients who had undergone treatment of the maxillary elements canal treatments. In all cases, the accidents occurred during the irrigation phase and were characterised by intracanal bleeding, ecchymosis, and swelling on the hemiface corresponding to the treated tooth. Antibiotics, paracetamol, NSAID, corticosteroids, and cold or warm compresses for oedema were prescribed to treat the symptoms of the accidents. Significant improvement of symptoms was observed in all patients after 5–6 days. Anatomic risk factors such as apical fenestration, root perforation, and large foramina were identified as possible risk factors for the accidents. After the accidents, clinicians applied endodontic procedures for which there is no scientific evidence to continue endodontic treatments, such as changing the type of irrigant or the irrigation method. Our results suggest that using a standardised approach to document each hypochlorite accident will allow researchers to collect more accurate and detailed data that can subsequently be used to identify potential risk factors and better manage the symptomatology of hypochlorite accidents.

Dental anxiety (DA) is defined as unreasonable apprehension toward dental procedures. About 4–20% of the worldwide adult population presents DA, with peaks of 30% in the younger population. Managing patients with dental anxiety and fear with a reliable and valid instrument is necessary to understand the multidimensional dimensions of dental fear. This work aimed to validate the Index of Dental Anxiety and Fear (IDAF-4C+) into Italian. Two hundred and eighty dental students attending an Italian university were enrolled. The IDAF-4C+ was translated by experts and a native English translator, blinded to the original version. The Modified Dental Anxiety Scale (MDAS) was used to assess the validity of IDAF-4C+. Spearman correlation coefficients and Exploratory Factorial Analysis (EFA) were used. Reliability was evaluated by Cronbach’s alpha. The reliability of the Italian version of IDAF-4C+ was good (Cronbach’s alpha = 0.88). Correlation between IDAF-4C+ and MDAS ranged between 0.42 to 0.68. From EFA, one factor explained 58.76% of the common variance. Women showed a higher level of dental fear. The Italian IDAF-4C+ is a valid and reliable tool to assess DA in any clinical context. This instrument allows for a proper understanding and management of DA, and therefore a better patient oral health-related quality of life and compliance with the dentist’s instructions.

Background: After the first lockdown, Italian dentists resumed their practice while handling several challenges. Reducing contagion risk by complying with the stringent measures recommended by the Italian Ministry of Health for dental activity while also balancing patient needs was a difficult task. This work aims to understand the procedures that were adopted in the second phase of the COVID-19 pandemic (5 May–30 September 2020) and the dentists’ expectations and concerns about returning to normalcy. Methods: A national survey with 38 questions was conducted from November 2020 to January 2021 and comparisons were performed among the five main Italian geographic areas. Results: Located mainly in northwest Italy, 1028 dentists were included in the survey. About 83% of the Italian dentists fully restarted their activities after the lockdown. The resumption was significantly marked in North Italy and the Center than in the South (p < 0.01). Over 80% adopted the recommended precautional guidelines, modifying them according to the specific dental treatment executed. Fifty percent of dentists were confident in returning to normalcy after the COVID-19 crisis. Many precautions adopted during the pandemic will be continued, especially in South Italy and the Islands (p < 0.01). Conclusions: Italian dentists reported excellent autonomous organizational skills and the maintaining of high-quality precautions during the reopening phase.