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Cultural heritage’s structural changes and damages can influence the mechanical behaviour of artefacts and buildings. The use of finite element methods (FEM) for mechanical analysis is largely used in modelling stress behaviour. The workflow involves the use of CAD 3D models and the use of non-uniform rational B-spline (NURBS) surfaces. For cultural heritage objects, altered by the time elapsed since their creation, the representation created with the CAD model may introduce an extreme level of approximation, leading to wrong simulation results. The focus of this work is to present an alternative method intending to generate the most accurate 3D representation of a real artefact from highly accurate 3D reality-based models, simplifying the original models to make them suitable for finite element analysis (FEA) software. The approach proposed, and tested on three different case studies, was based on the intelligent use of retopology procedures to create a simplified model to be converted to a mathematical one made by NURBS surfaces, which is also suitable for being processed by volumetric meshes typically embedded in standard FEM packages. This allowed us to obtain FEA results that were closer to the actual mechanical behaviour of the analysed heritage asset.

Proper documentation is fundamental to providing structural health monitoring, damage identification and failure assessment for Cultural Heritage (CH). Three-dimensional models from photogrammetric and laser scanning surveys usually provide 3D point clouds that can be converted into meshes. The point clouds usually contain noise data due to different causes: non-cooperative material or surfaces, bad lighting, complex geometry and low accuracy of the instruments utilized. Point cloud denoising has become one of the hot topics of 3D geometric data processing, removing these noise data to recover the ground-truth point cloud and adding smoothing to the ideal surface. These cleaned point clouds can be converted in volumes with different algorithms, suitable for different uses, mainly for structural analysis. This paper aimed to analyse the geometric accuracy of algorithms available for the conversion of 3D point clouds into volumetric models that can be used for structural analyses through the FEA process. The process is evaluated, highlighting problems and difficulties that lie in poor reconstruction results of volumes from denoised point clouds due to the geometric complexity of the objects.

Digital Twin (DT) technology is a pivotal innovation within the built environment industry, facilitating digital transformation through advanced data integration and analytics. DTs have demonstrated significant benefits in building design, construction, and asset management, including optimising lifecycle energy use, enhancing operational efficiency, enabling predictive maintenance, and improving user adaptability. By integrating real-time data from IoT sensors with advanced analytics, DTs provide dynamic and actionable insights for better decision-making and resource management. Despite these promising benefits, several challenges impede the widespread adoption of DT technology, such as technological integration, data consistency, organisational adaptation, and cybersecurity concerns. Addressing these challenges requires interdisciplinary collaboration, standardisation of data formats, and the development of universal design and development platforms for DTs. This paper provides a comprehensive review of DT definitions, applications, capabilities, and challenges within the Architecture, Engineering, and Construction (AEC) industries. This paper provides important insights for researchers and professionals, helping them gain a more comprehensive and detailed view of DT. The findings also demonstrate the significant impact that DTs can have on this sector, contributing to advancing DT implementations and promoting sustainable and efficient building management practices. Ultimately, DT technology is set to revolutionise the AEC industries by enabling autonomous, data-driven decision-making and optimising building operations for enhanced productivity and performance.

In the presence of architecturally significant ruins, restoring and disseminating the idea of a testimony that has survived the destructive work of time is a cultural and social necessity that the use of advanced methods and tools allows to communicate in a timely and comprehensive manner. The integration of 3D surveying techniques and digital information production and management processes (graphic and alphanumeric, i.e., geometric information) makes it possible to put in place multifaceted and effective strategies. The article aims at describing the process of data acquisition (using applied photogrammetry) of the remains of a medieval cloister located on the outskirts of ancient Oppido Mamertina (RC, Italy). The use of the acquired point cloud, cleaned and optimised, made it possible to extract suitable orthophotos from which to derive the matrix profiles of the vaulted roof system. The information organisation of the model, which can be queried on time despite the generic level of detail, leads us to meditate on the change taking place in the field of documentation for urban environmental design and maintenance.

BackgroundProteasome inhibitors (PIs), including carfilzomib, potentiate the activity of selinexor, a novel, first-in-class, oral selective inhibitor of nuclear export (SINE) compound, in preclinical models of multiple myeloma (MM).MethodsThe safety, efficacy, maximum-tolerated dose (MTD) and recommended phase 2 dose (RP2D) of selinexor (80 or 100 mg) + carfilzomib (56 or 70 mg/m2) + dexamethasone (40 mg) (XKd) once weekly (QW) was evaluated in patients with relapsed refractory MM (RRMM) not refractory to carfilzomib.ResultsThirty-two patients, median prior therapies 4 (range, 1–8), were enrolled. MM was triple-class refractory in 38% of patients and 53% of patients had high-risk cytogenetics del(17p), t(4;14), t(14;16) and/or gain 1q. Common treatment-related adverse events (all/Grade 3) were thrombocytopenia 72%/47% (G3 and G4), nausea 72%/6%, anaemia 53%/19% and fatigue 53%/9%, all expected and manageable with supportive care and dose modifications. MTD and RP2D were identified as selinexor 80 mg, carfilzomib 56 mg/m2, and dexamethasone 40 mg, all QW. The overall response rate was 78% including 14 (44%) ≥ very good partial responses. Median progression-free survival was 15 months.ConclusionsWeekly XKd is highly effective and well-tolerated. These data support further investigation of XKd in patients with MM.

Background Daratumumab, a CD38 monoclonal antibody, has demonstrated efficacy as monotherapy and combination therapy across several indications, both among newly-diagnosed and refractory patients with multiple myeloma (MM). However, there is limited evidence on treatment patterns and effectiveness of daratumumab in the real-world setting, particularly in first line (1 L). This study aimed to describe real-world treatment patterns and clinical outcomes among patients initiating daratumumab across different lines of therapy. Methods A retrospective chart review of adult patients with MM initiating daratumumab between November 2015 and March 2021 was conducted at two clinical sites in the United States. De-identified patient-level data were abstracted in an electronic case report form. Patient characteristics and treatment patterns were described. Clinical outcomes including overall response rate (ORR), progression-free survival, and time to next line of therapy were reported using descriptive statistics and stratified by line of therapy (1 L, second line [2 L] or third line or later [3 L+]). A sub-group analysis evaluated treatment patterns and ORR among patients re-treated with daratumumab. Results A total of 299 patients were included in the study (mean age: 68 years; 55% male). Among them, 26 were 1 L patients, 66 were 2 L patients, and 207 were 3 L+ patients; 110 patients (36.8%) received a stem cell transplant prior to daratumumab initiation. The mean duration of follow-up was 10 months among 1 L patients and 19 months among 2 L and 3 L+ patients. Patients who initiated daratumumab in 1 L had a 100% ORR, while those initiating in 2 L and 3 L+ had an ORR of 78.8 and 65.2%, respectively. Among re-treated patients, ORR was 66.7% during the first treatment segment, and 52.9% during the second treatment segment. Kaplan-Meier rates of progression-free survival at 12 months were 89.9, 75.2, and 53.1% among patients who initiated daratumumab in 1 L, 2 L, and 3 L+, respectively. Kaplan-Meier rates of time to next line of therapy at 12 months were 94.1, 73.4, and 50.0% among patients who initiated daratumumab in 1 L, 2 L, and 3 L+, respectively. Conclusions These findings suggest that daratumumab-based regimens are an effective treatment option across all lines of therapy, with highest response rate in 1 L.

A rare T-cell lymphoma after chimeric antigen receptor (CAR) T-cell therapy for myeloma was linked to CCR4 overexpression and vector integration, which highlights the need for monitoring after CAR T-cell therapy.

Through a non-contact survey methodology, based on image-based techniques, the authors digitally ‘build’ a three-dimensional hypothesis of a monumental complex carved on a first-century AC marble tombstone. Guided by the mathematical rationality recognised in the artefact, the paper illustrates the reasons for the reconstructive choices and then proposes a reflection on the architectural contents. The ultimate goal focuses on the potential use of the digital product, which, thanks to and by virtue of the use of dedicated platforms, promotes strategies that include identity values by superimposing technical, social, and economic aspects. The setting up of collaborative spaces programmed with different strategies can effectively support the cognitive experience by verifying the possibility of “remedying” contents that, in our case, direct the study, dissemination, and protection of cultural heritage according to the most recent UNESCO recommendations.

Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy and durable responses in patients with relapsed/refractory multiple myeloma (RRMM). However, the outcomes with ide-cel in patients with extramedullary disease (EMD) remain incompletely characterized. We included patients with RRMM treated with ide-cel between May 2021 and April 2023 across 11 US academic institutions. Visceral or soft tissue lesions non-contiguous from bone was classified as EMD. Time-to-event analyses were performed from date of ide-cel infusion. Among 351 patients, 84 (24%) had EMD prior to infusion. The median follow-up from ide-cel infusion was 18.2 months (95% CI: 17-19.3). The day 90 overall response rates (ORR) were 52% vs. 82% for the EMD and non-EMD cohorts, respectively ( p  < 0.001). The median progression-free survival (PFS) was 5.3 months (95% CI: 4.1–6.9) for the EMD cohort vs. 11.1 months (95% CI: 9.2–12.6; p  < 0.0001) for the non-EMD cohort. In a multivariable analysis, EMD was an independent predictor of inferior PFS [hazard ratio 1.5 (1.1–2.2), p  = 0.02]. The median overall survival was 14.8 months [95% CI: 9-Not reached (NR)] vs. 26.9 months (26.3 vs. NR, p  = 0.006) for the EMD and non-EMD cohorts, respectively. Extramedullary disease represents an independent predictor of inferior day 90 ORR and PFS among patients treated with ide-cel.

This paper explores the possibility of counteracting the crisis of culture and institutions by investing in the identity values of the user-actor within digital spaces built for the purpose. The strategy is applied to the analysis of three Catalan cloisters (Spain), with a focus on the representation of the cloister of Sant Cugat (Barcelona). Heuristic picklocks are found in the semantic richness proposed by Marius Schneider exclusively on the verbal level. The authors interpret the contents and transcribe them into graphic signs and digital denotations of sounds and colors. They organize proprietary ontologies, or syntagmatic lines, to be entrusted to the management of computer algorithms. The syncretic culture that characterized the medieval era allowed the ability to mediate science and faith to be entrusted to the mind of the praying monk alone in every canonical hour. The hypothesis that a careful direction has programmed the ways in which to orient souls to “navigate by sight” urges the authors to find the criteria that advanced statistics imitates to make automatic data processing “Intelligent”. In step with the times and in line with the most recent directions for the Safeguarding of Heritage, the musical, astral, and narrative rhythms feared by Schneider are used to inform representative models, to increase not only the visual perception of the user (XR Extended Reality) but also to solicit new analogies and illuminating associations. The results return a vision of the culture of the time suitable for shortening the distances between present and past, attracting the visitor and, with him, the resources necessary to protect and enhance the spaces of the Romanesque era. The methodology goes beyond the contingent aspect by encouraging the ‘remediation’ of contents with the help of machine learning.