The paramagnetic gadolinium(III) ion is used as contrast agent in magnetic resonance (MR) imaging to improve the lesion detection and characterization. It generates a signal by changing the relaxivity of protons from associated water molecules and creates a clearer physical distinction between the molecule and the surrounding tissues. New gadolinium-based contrast agents displaying larger relaxivity values and specifically targeted might provide higher resolution and better functional images. We have synthesized the gadolinium(III) complex of formula [Gd(thy)2(H2O)6](ClO4)3·2H2O (1) [thy = 5-methyl-1H-pyrimidine-2,4-dione or thymine], which is the first reported compound based on gadolinium and thymine nucleobase. 1 has been characterized through vis-IR, SEM-EDAX and single-crystal X-ray diffraction techniques, and its magnetic and relaxometric properties have been investigated by means of SQUID magnetometer and MR imaging phantom studies, respectively. On the basis of its high relaxivity values, this gadolinium(III) complex can be considered a suitable candidate for contrast enhanced magnetic resonance imaging.

Atrophy quantification is fundamental for understanding brain development and diagnosing and monitoring brain diseases. FSL-SIENA is a well-known fully-automated method that has been widely used in brain magnetic resonance imaging studies. However, intensity variations arising during image acquisition that may compromise evaluation, analysis and even diagnosis. In this work, we study whether intensity standardisation can improve longitudinal atrophy quantification. We considered seven methods comprising z-score, fuzzy c-means, Gaussian mixture model, kernel density, histogram matching, white stripe, and removal of artificial voxel effects by linear regression (RAVEL). We used a total of 330 scans from two publicly-available datasets, ADNI and OASIS. In scan-rescan assessments, that measures robustness to subtle imaging variations, intensity standardisation did not compromise the robustness of FSL-SIENA significantly (p>0.1). In power analysis assessments, that measures the ability to discern between two groups of subjects, three methods led to consistent improvements in both datasets with respect to the original: fuzzy c-means, Gaussian mixture model, and kernel density estimation. Reduction in sample size using these three methods ranged from 17% to 95%. The performance of the other four methods was affected by spatial normalisation, skull stripping errors, presence of periventricular white matter hyperintensities, or tissue proportion variations over time. Our work evinces the relevance of appropriate intensity standardisation in longitudinal cerebral atrophy assessments using FSL-SIENA.

People counting applications have been used in diverse applications. The ability and accuracy of thermal imaging over conventional image cameras has led to the implementation of thermal cameras in people counting applications. This paper present a thermal people counting smart glass windows. The people counting application would be remotely monitored from a single centralized PC station as it’s connected to a multiplex of mass monitoring of 20 thermal camera, all embedded into different glass windows. The thermal cameras would then be able to detect body temperatures of all individuals who pass through any of the camera range and also count the numbers of people who passed through the camera range. The data gotten can then be further utilized in various ways, example is in the control of air conditioning and lightening.

Electron Channeling Contrast Imaging (ECCI) is becoming a powerful tool in Materials Science for characterizing deformation defects. Dislocations observed by ECCI in Scanning Electron Microscope, exhibit several features depending on the crystal orientation relative to the incident beam (white/black line on a dark/bright background). In order to bring new insights concerning these contrasts, we report an original theoretical approach based on the dynamical diffraction theory. Our calculations led, for the first time, to an explicit formulation of the backscattered intensity as a function of various physical and practical parameters governing the experiment. Intensity profiles are modeled for dislocations parallel to the sample surface for different channeling conditions. All theoretical predictions are consistent with experimental results.

Three patients with multi-year histories of relapsing and remitting Lyme disease and associated co-infections despite extended antibiotic therapy were each given double dose dapsone combination therapy (DDD CT) for a total of 7-8 weeks. At the completion of therapy, all three patients major Lyme symptoms remained in remission for a period of 25-30 months. In conclusion, Double dose dapsone therapy could represent a novel and effective anti-infective strategy in chronic Lyme disease/PTLDS, especially in those individuals who have failed regular dose dapsone combination therapy (DDS CT) or standard antibiotic protocols. A randomized, blinded, placebo-controlled trial is warranted to evaluate the efficacy of DDD CT in those individuals with chronic Lyme disease/PTLDS.

To address the large hysteresis and susceptibility to instability in high-speed deposition fusion moulding (FDM) 3D printing’s temperature control, this paper proposes an improved ant-lion optimization algorithm (OCALO) to optimize the PID parameters.The improvement aims to solve the problem that the traditional ant-lion optimization algorithm (ALO) reduces the population diversity and tends to fall into the local optimal solution when it is close to the global optimal solution.The generation of the initial solution is enhanced by the introduction of a new Tent-Logistic-Cotangent composite chaotic mapping. This integration into Elite Opposition-Based Learning aids in optimizing population diversity. Concurrently, the incorporation of cosine factors of a specified parameter into the elitist formula of the traditional ALO algorithm is aimed at reducing the tendency of ants to randomly gravitate towards ant-lions with lower fitness values. This adjustment helps in balancing the exploration-exploitation trade-off in the algorithmic process. Compared with two existing classical algorithms and three improved ALO algorithms, the algorithm improves the convergence speed, global search ability and the ability to jump out of the local optimal solution. The improved algorithm was combined with PID control to design an OCALO-PID temperature controller and simulated on a high-speed 3D printing temperature model identified by modelling. The results show that the method improves the transient and steady-state performance of reactor temperature control with good control accuracy and robustness. Finally, the proposed algorithm is applied to a physical experimental platform to verify the feasibility of the algorithm.

Three-dimensional (3D) and four-dimensional (4D) printing emerged as the next generation of manufacturing techniques, spanning several research areas such as engineering, chemistry, biology, computing, and materials science. Three-dimensional printing allows the manufacture of complex shapes with high precision, by adding layer by layer of different materials. The use of smart materials that change shape or color, produce an electrical current, become bioactive, or perform an intended function in response to an external stimulus. Shape memory materials (SMMs) in 3D printing technology have attracted a lot of attention due to their ability to respond to external stimuli, leading this technology towards an emerging area of research, "4D printing technology." The core part of this review summarizes the effect of the main external stimuli on 4D textile materials followed by the main applications 4D printed textiles can change their shape over time due to external stimuli such as temperature.

Sacroiliac (SI) joint dysfunction can lead to debilitating pain but can be treated with minimally invasive sacroiliac joint fusion (SIJF). This treatment is commonly performed using 2D fluoroscopic guidance. This makes placing the implants without damaging surrounding neural structures challenging. Virtual surgical planning (VSP) using simulated fluoroscopic images may improve perioperative guidance. This article describes a workflow with VSP in SIJF using simulated fluoroscopic images and evaluates achieved implant placement accuracy. Routinely collected survey data on the added value of VSP were also evaluated. Ten interventions were performed on 10 patients by the same surgeon, comprising 30 implants; the median age was 39 years, and all patients were female. The overall mean implant placement accuracy was 4.9 ± 1.26 mm and 4.0 ± 1.44°. There were no malpositioning complications. The VSP helped the surgeon understand the anatomy and determine the optimal position and length of the implants. The average Likert scale score of the survey was 4.7, suggesting a positive role of VSP for SIJF. Planned positions of the implants could be reproduced in surgery with clinically acceptable accuracy and VSP was a valuable asset for the surgeon.

Ledge formation presents a significant challenge in endodontic treatment. Yet, there is still a lack of educational tooth models for hands-on practice. This study aimed to create and evaluate a tooth model for ledge management practice. A natural tooth with curved roots was collected for scientific use under ethics committee approval. Following initial root canal preparation, the tooth was scanned using micro-computed tomography (μCT) and 3D reconstructed. A K-file, created via computer-aided design (CAD), was partly inserted into the root canal wall of the 3D-reconstructed tooth. By subtracting the K-file from the tooth, a tooth model with a root canal ledge was produced. The models were then 3D printed for a hands-on workshop. A seven-item Likert scale questionnaire was administered to 20 postgraduate students and 10 endodontists to assess the model's quality and training effectiveness. The feedback from both students and experts was positive, with no statistically significant differences found between the two groups (p > 0.05). This novel tooth model is expected to address the existing gap in endodontic education and provide benefits for dental practitioners in future applications.

Regeneration of biological tissues in medicine is challenging, and 3D bioprinting offers an innovative way to create functional multicellular tissues. One common way in bioprinting is bioink which is one type of the cell-loaded hydrogel. For clinical application, however, the bioprinting still suffers from satisfactory performance, e.g. in vascularization, effective antibacterial, immunomodulation and regulation of collagen deposition. Many studies have incorporated different bioactive materials into the 3D printed scaffolds to optimize the bioprinting. Here, we review a variety of additives added to the 3D bioprinting hydrogel. The underlying mechanisms and methodology for biological regeneration are important and will provide useful basis for future research.

Cancer invasion through basement membranes represents the initial step of tumor dissemination and metastasis. However, little is known about how human cancer cells breach basement membranes. Here, we used a 3-dimensional in vitro invasion model consisting of cancer spheroids encapsulated by a basement membrane and embedded in 3D collagen gels to visualize the early events of cancer invasion by confocal microscopy and live-cell imaging. Human breast cancer cells generated large numbers of basement membrane perforations, or holes, of varying sizes that expanded over time during cell invasion. We used a wide variety of small molecule inhibitors to probe the mechanisms of basement membrane perforation and hole expansion. Protease inhibitor treatment (BB94), led to a 63% decrease in perforation size. After myosin II inhibition (blebbistatin), basement membrane perforation area decreased by only 15%. These treatments produced correspondingly decreased cellular breaching events. Interestingly, inhibition of actin polymerization dramatically decreased basement membrane perforation by 80% and blocked invasion. Our findings suggest that human cancer cells can primarily use proteolysis and actin polymerization to perforate the BM and to expand perforations for basement membrane breaching, with a relatively small contribution from myosin II contractility.

Additive manufacturing (AM) are used in several industries such as automotive, aerospace, and medical sciences. One of the most common devices used in additive manufacturing is fused deposition modeling (FDM) 3D printers. This fabrication method has different inputs that affect the quality of the parts. In this research, the bending fatigue properties of polylactic acid (PLA) biomaterial made with a 3D printer are investigated. To demonstrate the influence of printing parameters on fatigue lifetime, standard specimens with nozzle diameters of 0.2-0.6 mm, extruder temperature of 180-240°C, and print speed of 5-15 mm/s were printed. After performing fully-reversed bending fatigue tests, it was found that printed specimens at 180°C have the best fatigue lifetime in most cases. Accordingly, fatigue behavior improved by reducing the nozzle diameter. Printing at lower temperatures also improved fatigue lifetime. The printing speed affected the slope of the S-N diagram, known as the fatigue strength exponent.

Desktop fused filament fabrication (FFF) 3D printers have been growing in popularity among hobbyist and professional users as a prototyping and low-volume manufacturing tool. One issue these printers face is the inability to determine when a defect has occurred rendering the print unusable. Several techniques have been proposed to detect such defects but many of these approaches are tailored to one specific fault (e.g., filament runout/jam), use expensive hardware such as laser distance sensors, and/or use machine vision algorithms which are sensitive to ambient conditions, and hence can be unreliable. This paper proposes a versatile, reliable, and low-cost system, named MTouch, to detect millimeter-scale defects that tend to make prints unusable. At the core of MTouch is an actuated contact probe designed using a low-power solenoid, magnet, and hall effect sensor. This sensor is used to check for the presence, or absence, of the printed object at specific locations. The MTouch probe demonstrated 100% reliability, which was significantly higher than the 74% reliability achieved using a commercially available contact probe (the BLTouch). Additionally, an algorithm was developed to automatically detect common print failures such as layer shifting, bed separation, and filament runout using the MTouch probe. The algorithm was implemented on a Raspberry Pi mini-computer via an Octoprint plug-in. In head-to-head testing against a commercially available print defect detection system (The Spaghetti Detective), the MTouch was able to detect faults 44% faster on average while only increasing the print time by 8.49%. In addition, MTouch was able to detect faults The Spaghetti Detective was unable to identify such as layer shifting and filament runout/jam.

In this paper we describe the potentialities of a tool for the visualization of experimental results directly on a three-dimensional model. The case study concerns the visualization of the results of a dynamic finite element analysis (FEA/FEM) applied to the calculation of seismic risk on works belonging to the Italian infrastructural heritage, specifically bridges, viaducts and overpasses. The project is based on finite element analysis performed on an exemplary set of 8 structures located on the Italian territory, performed by means of the open-source software framework OpenSees, according to the guidelines indicated in the Technical Standards for Construction NTC08. The application created for this project is classifiable as a webGIS, since all data are georeferenced and visualized on a map through an application executed through a browser. The graphical interface displays the interested works on the map of the Italian territory and allows to select them by mouse click. Following the selection, a 3D rendering of the model of the work and the surrounding terrain is shown, in which the results of the analysis are represented using color gradients directly on the three-dimensional model. The necessary tools are present for the selection of the type of result and for the animation in real time of the response of the work to the seismic action. The 3D representation is freely navigable by the user thanks to intuitive tools of panning, rotation and zoom through mouse and keyboard. The application takes advantage of HTML5, CSS and Javascript to show graphical features such as Cartesian diagrams of accelerograms used in modal analysis.

Orofacial injuries are common occurrences during contact sports activities; however, there is an absence of data regarding the performance of hybrid occlusal splint mouthguards, especially during compressive loading. To evaluate the total deformation and stress concentration, a skull model was selected and duplicated to receive two different designs of mouthguard devices: one model received a conventional custom-made mouthguard (MG) with 4-mm thickness and the other received a novel hybrid occlusal splint-mouthguard (HMG) with the same thickness. Both models were subdivided into finite elements. The frictionless contacts were used, and a nonlinear analysis was performed simulating the compressive loading in occlusion. The results were presented in von-Mises stress maps (MPa) and Total Deformation (mm). A higher stress concentration in teeth was observed for the model with the conventional MG, while the HMG design displayed a promising mechanical response with lower stress magnitude. The HMG de-sign displayed a higher magnitude of stress on its occlusal portion than the MG design. The hybrid mouthguard (HMG) reduced (1) jaw displacement during chewing and (2) the generated stresses in maxil-lary and mandibular teeth.

Micro-blade design is an important factor in the cutting of single cells and other biological structures. This paper describes the fabrication process of three dimensional (3D) micro-blades for the cutting of single cells in a microfluidic “guillotine” intended for fundamental wound repair and regeneration studies. Our microfluidic guillotine consists of a fixed 3D micro-blade centered in a microchannel to bisect cells flowing through. We show that the Nanoscribe two-photon polymerization direct laser writing system is capable of fabricating complex 3D micro-blade geometries. However, structures made of the Nanoscribe IP-S resin have low adhesion to silicon, and they tend to peel off from the substrate after at most two times of replica molding in poly(dimethylsiloxane) (PDMS). Our work demonstrates that the use of a secondary mold replicates Nanoscribe printed features faithfully for at least 10 iterations. Finally, we show that complex micro-blade features can generate different degrees of cell wounding and cell survival rates compared with simple blades possessing a vertical cutting edge fabricated with conventional 2.5D photolithography. Our work lays the foundation for future applications in single cell analyses, wound repair and regeneration studies, as well as investigations of the physics of cutting and the interaction between the micro-blade and biological structures.

Recent years witnessed progressive broadening of the practical use of 3D-printed aluminium alloy parts, in particular for specific aerospace applications where weight saving is of great importance. Selective laser melting (SLM) is an intrinsically multi-parametric fabrication technology that offers multiple means of controlling mechanical properties (elastic moduli, yield strength, ductility) through the control over grains size, shape, and orientation. Ultimately, this approach implies that structural elements can be purposefully fabricated to reinforce specific zones and directions where higher mechanical loads are anticipated by design. Targeted control over mechanical properties is achieved through the tuning of 3D-printing parameters and may even obviate the need of heat treatment or mechanical post-processing. Systematic studies of grain structure for different printing orientation with the help of EBSD techniques in combination with mechanical testing at different dimensional levels are the necessary first steps to implement this agenda. Samples of 3D-printable Al-Mg-Si RS-333 alloy were fabricated in 3 orientations with respect to the principal build direction and the fast laser beam scanning direction. Sample structure and proper-ties were investigated using a number of techniques, including EBSD, in situ SEM tensile testing, roughness measurements and nanoindentation. The as-printed samples we found to display strong variation in Young’s modulus values from nanoindentation (from 43 to 66 GPa) and tensile tests (from 54 to 75 GPa), yield stress and ultimate tensile strength (100…195 and 130…220 MPa) in different printing orientations, and almost constant hardness of about 0.8 GPa. A further preliminary study was conducted of the effect of surface finishing on the mechanical performance. Surface polishing appears to reduce Young’s modulus and yield strength, but improves ductility, whereas the influence of sand blasting is more controversial. The experimental results are dis-cussed in connection with the grain morphology and orientation.

The 3D reconstruction method using RGB-D camera has a good balance in hardware cost, point cloud quality and automation. However, due to the limitation of inherent structure and imaging principle, the acquired point cloud has problems such as a lot of noise and difficult registration. This paper proposes a three-dimensional reconstruction method using Azure Kinect to solve these inherent problems. Shoot color map, depth map and near-infrared image of the target from six perspectives by Azure Kinect sensor. Multiply the 8-bit infrared image binarization with the general RGB-D image alignment result provided by Microsoft to remove ghost images and most of the background noise. In order to filter the floating point and outlier noise of the point cloud, a neighborhood maximum filtering method is proposed to filter out the abrupt points in the depth map. The floating points in the point cloud are removed before generating the point cloud, and then using the through filter filters out outlier noise. Aiming at the shortcomings of the classic ICP algorithm, an improved method is proposed. By continuously reducing the size of the down-sampling grid and the distance threshold between the corresponding points, the point clouds of each view are continuously registered three times, until get the complete color point cloud. A large number of experimental results on rape plants show that the point cloud accuracy obtained by this method is 0.739mm, a complete scan time is 338.4 seconds, and the color reduction is high. Compared with a laser scanner, the proposed method has considerable reconstruction accuracy and a significantly ahead of the reconstruction speed, but the hardware cost is much lower and it is easy to automate the scanning system. This research shows a low-cost, high-precision 3D reconstruction technology, which has the potential to be widely used for non-destructive measurement of crop phenotype.

Metal 3D printing technology is a promising manufacturing method. The quality of the printed product can pass for mechanical application, if the anisotropy of the microstructure, imperfections, deformation, and residual stress of the printed sample could be lower than the appropriate level or if they are fully illuminated. Thermal stress is one of the significant reasons for deformation in the 3D printed samples. Thermal stresses are the direct consequence of the local temperature gradient. In this research, the effect of the temperature printer’s chamber (from room temperature to 900 C) was studied on thermal stress and subsequent total deformation in the printed sample. The printed sample is a six-layers-printed walk, which could be considered as a building block of other complex shapes and give us inside about deformation. The computational results show a meaningful reduction in thermal stress and deformation at the higher temperature of the printer’s chamber. The lower final deformation of the printed sample is an important subject, especially for samples with complex shapes.

Solar3D is an open-source software application designed to interactively calculate solar irradiation at three-dimensional (3D) surfaces in a virtual environment constructed with combinations of 3D city models, digital elevation models (DEMs), digital surface models (DSMs) and feature layers. The GRASS GIS r.sun solar radiation model computes solar irradiation based on two-dimensional (2D) raster maps for given day, latitude, surface and atmospheric conditions. With the increasing availability of 3D city models and demand for solar energy, there is an urgent need for better tools to computes solar radiation directly with 3D city models. Solar3D extends GRASS GIS r.sun from 2D to 3D by feeding the model with input, including surface slope, aspect and time-resolved shading, that is derived directly from the 3D scene using computer graphics techniques. To summarize, Solar3D offers several new features which, as a whole, distinguish itself from existing 3D solar irradiation tools: (1) the ability to consume massive heterogeneous 3D city models, including massive 3D city models such as oblique airborne photogrammetry-based 3D city models (OAP3Ds or integrated meshes); (2) the ability to perform near real-time pointwise calculation for duration from daily to annual; (3) the ability to integrate and interactively explore large-scale heterogeneous geospatial data. (4) the ability to calculate solar irradiation at arbitrary surface positions including at rooftops, facades and the ground. Solar3D is publicly available at https://github.com/jian9695/Solar3D.

The aim of this study is to provide a detailed strategy for Safe-by-Design (SbD) 3D printed lab-on-a-chip (LOC) device manufacturing, using Fused Filament Fabrication (FFF) technology. At first, the applicability of FFF in lab-on-a-chip device development is briefly discussed. Subsequently, a methodology to categorize, identify and implement SbD measures for FFF is suggested. Furthermore, the most crucial health risks involved in FFF processes are examined, placing the focus on the examination of ultrafine particle (UFP) and Volatile Organic Compound (VOC) emission hazards. Thus, a SbD scheme for lab-on-a-chip manufacturing is provided, while also taking into account process optimization for obtaining satisfactory printed LOC quality. This work can serve as a guideline for the effective application of FFF technology for lab-on-a-chip manufacturing through the safest applicable way, towards a continuous effort to support sustainable development of lab-on-a-chip devices through cost-effective means.

The liquid-vapor phase change lattice Boltzmann method is used to investigate the pinning-depinning mechanism of the contact line during droplet evaporation on the stripe-patterned surfaces in 3D space. Considering the curvature of the contact line and the direction of the unbalanced Young’s force, the local force balance theory near the stripe boundary is proposed to explain the steady state of the droplets on the stripe-patterned surfaces. An equation is proposed to evaluate the characteristic contact angle of the stabilized droplets. During the evaporation of the droplet, the stick-slip-jump behavior and the CCR-Mixed-CCA mode can be well captured by the lattice Boltzmann simulation. When the contact line is pinned to the stripe boundary, the contact line in the direction perpendicular to the stripes is slowly moving while the curvature of the contact line is gradually increasing. The gradually increasing curvature of the contact line accelerates the movement of the contact line, and the final contact line is detached from the stripe boundary. The research results provide theoretical support and guidance for the design, improvement and application of patterned surfaces in the field of micro-fluidic and evaporation heat transfer.

Non-destructive testing of metallic objects that may contain embedded defects of different sizes is an important application in many industrial branches for quality control. Most of these techniques allow defect detection and its approximate localization, but very few give enough information for its 3D reconstruction. Here we present a hybrid laser – transducer system that combines remote laser-generated ultrasound excitation and non-contact ultrasonic transducer detection. This fully non-contact method gives access to separating scan areas on different object’s faces and defect details from different angles/perspectives can be analysed. This hybrid system can analyse the whole object’s volume data and allow a 3D reconstruction image of the embedded defects. As a novelty for the signal processing improvement, we use a 2D apodization window filtering technique, applied along with the synthetic aperture focusing algorithm in order to remove the undesired effects of side lobes and wide-angle reflections of propagating ultrasound waves, thus, enhancing the resulting 3D image of the defect. We provide both qualitative and quantitative volumetric results with high accuracy and resolution compared with conventional techniques.

Public participation is significant for the success of any urban planning project. However, most members of the general public are not planning professionals and may not understand the technical details of a 2D paper-based plan, which might hamper their participation. One way to expand the participation of citizens is to present plans in well-designed, user-friendly and interactive platforms that allow participation regardless of the technical skills of the participants. This paper investigates the impacts of the combined use of 3D visualization and E-participation on public participation in Kisumu, Kenya. A 3D City model, created with CityEngine2016, was exported into a web-based geo-portal and used as a Planning Support System in two stakeholder workshops in order to evaluate its usability. For e-participation, 300 questionnaires given out to planning practitioners. Five indicators were developed for evaluating the usability of the 3D model while the usability of e-participation was evaluated using communication, collaboration and learning as indicators. Results showed that effectiveness and efficiency varies within different professional groups while the questionnaires showed strong preference for e-participation methods, especially SMSs/USSDs and emails. The study concludes that the use of 3D visualization and E-participation has the potential for improving the quality and quantity of public participation and recommends further research on the subject.

Buildability, i.e. the ability of a deposited material bulk to retain its dimmensions under increasing load, is an inherent prerequisite for formwork-free digital construction (DC). Since DC processes are relatively new, no standard methods of characterization are available yet. The paper at hand presents practice-oriented buildabilty criteria by taking various process parameters and construction costs into consideration. In doing so, direct links between laboratory buildability tests and target applications are established. A systematic basis for calculating the time interval (TI) to be followed during laboratory testing is proposed for the full-width printing (FWP) and filament printing (FP) processes. The proposed approach is validated by applying it to a high-strength, printable, fine-grained concrete. Comparative analyses of FWP and FP revealed that to test the buildability of a material for FP processes, higher velocities of the printhead should be established for laboratory tests in comparison to those needed for FWP process, providing for equal construction rates.

Convolutional Neural Networks (CNNs) are often criticized for their lack of transparency, acting as 'black boxes' in decision-making, a challenge compounded by class imbalance in ECG datasets, which limits their clinical application. This study introduces a CNN-based ECG signal classification model that enhances interpretability and addresses class imbalance through the Synthetic Minority Over-sampling Technique (SMOTE). The model also integrates Uniform Manifold Approximation and Projection (UMAP) for dimensionality reduction and SHAP value analysis, facilitating the visualization of decision boundaries and the assessment of feature contributions. Our evaluation using the MIT-BIH Arrhythmia Database highlights the model's high performance, with accuracy and precision nearing 1.00 for Normal ECG (NOR), Left Bundle Branch Block (LBBB), Right Bundle Branch Block (RBBB), and Ventricular Premature Beat (PVC) in the six-class task. In the ten-class task, the model demonstrated robustness, particularly with an accuracy of 0.9846, precision of 0.9783, recall of 0.9736, and F1 score of 0.9760 in Pacemaker Fusion Beat (PFHB), supported by an AUC of 0.9999 and AP of 0.9885. These results underscore the model's efficacy in cardiac rhythm recognition and resilience to class imbalance. Future research will explore sophisticated model architectures and feature extraction methods to enhance the model's generalization and clinical applicability for early heart disease diagnosis and personalized treatment.

Background/Objectives: Although the role of F-18 FDG PET/CT imaging is well established in oncology, its diagnostic value in routine monitoring for recurrent colorectal cancer (CRC) is still controversial. The aim was to evaluate the diagnostic value of FDG PET/CT in detecting recurrent CRC in correlation with CEA, CA 19-9 levels, and conventional imaging modalities (CIM). Methods: Between 2009 and 2023, we retrospectively studied 134 CRC patients referred for FDG PET/CT imaging on the suspicion of recurrence based on elevated CEA and/or CA 19-9, and/or equivocal radiological findings. According to the Institutional Tumor Board CRC protocol, after initial treatment which was dependent on TNM stage (neoadjuvant therapy, primary resection or adjuvant treatment), patients underwent a standard 5-year surveillance including CEA and CA 19-9 measurements, CIM, and colonoscopy every 6 months. The statistics including univariate and multivariable analyses were conducted using the IBM SPSS 20.0 statistical software. P-values <0.05 were considered statistically significant. Results: Recurrent CRC was confirmed in 54/134 (40.3%) patients with elevated tumor markers. FDG PET/CT shows high diagnostic performance in detecting recurrent CRC with sensitivity, specificity, PPV, NPV, and accuracy of 94.4%, 82.5%, 78.5%, 95.7%, and 87.3%, respectively. The CEA shows a high sensitivity of 98.1%, but both low specificity and accuracy of 15% and 48.5%, respectively. The sensitivity, specificity, and accuracy, for CA 19-9 and CIM for the correct diagnosis in CRC patients were: 44.4%, 67.5%, 58.2%, and 51.9%, 98.8%, 79.9%, respectively. The AUC for FDG PET/CT, elevated CEA levels, CIM, and elevated CA 19-9 levels was 0.885 (95% CI: 0.824-0.946; p<0.001), 0.844 (95% CI: 0.772-0.916; p<0.001), 0.753 (95% CI: 0.612-0.844; p<0.001); and 0.547 (95% CI: 0.442-0.652; p=0.358). Univariate analysis shows that both FDG PET/CT- and CIM-positive results were highly associated with CRC recurrence (p<0.001 and p<0.001, respectively), while gender, mucinous tumor type, presence of initial lymph node metastasis (N+), and presence of initial distant metastasis (M+) have no significance (p=0.211, p=0.158, p=0.583, and p=0.201, respectively). Our multivariate analysis shows that independent predictors for CRC recurrence are: positive FDG PET/CT scans (p<0.001), positive CIM results (p=0.001) and elevated CA19-9 levels (p=0.023). Although CA 19-9 was not detected as a statistically significant predictor in the univariate analysis (p=0.358), in a multivariate analysis it was recognized as a significant predicting factor in detecting CRC recurrence (p=0.023). Conclusions: FDG PET/CT shows a high diagnostic efficacy in CRC recurrence detection, in correlation with CEA levels, CA 19-9 levels, and CIM. This imaging modality should be routinely integrated into the postoperative follow-op in patients with elevated tumor markers.

18F-fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET-CT) is increasingly used in the diagnosis, prognosis, staging, and treatment monitoring of many tumor types. However, only a small number of studies have reported the use of 18F-FDG PET-CT in intrahepatic cholangiocarcinoma (ICC). This study aimed to examine the accuracy of tumor staging in ICC by using 18F-FDG PET-CT. Between January 2009 and December 2020, patients with suspected ICC were retrospectively enrolled in the study and underwent imaging. The sensitivity and specificity of 18F-FDG PET-CT, CT, and magnetic resonance imaging (MRI) in detecting tumors, satellite focus, vascular invasion, and lymph node metastases were analyzed. The efficacy of 18F-FDG PET-CT for tumor staging was evaluated. Of the 110 patients who were enrolled in the study, 52 underwent surgical treatment and 45 were histologically diagnosed with ICC. When compared with CT or MRI, 18F-FDG PET-CT had similar sensitivity and specificity values for diagnosing satellite focus and vascular and bile duct invasion; however, PET-CT showed higher accuracy in diagnosing regional lymph node metastases. The accuracy of tumor staging by 18F-FDG PET-CT was higher than that by CT/MRI. Thus, 18FDG PET-CT may support tumor staging in ICC.

Background: Post-operative pain and swelling are frequently observed after sinus lift procedures. The aim of the present study was a clinical evaluation of swelling and pain of two sinus lift different flaps technique measured through visual analogue scale (VAS), verbal rating scale (VRS) and infrared thermal imaging (i.e., thermography). Methods: A randomized controlled trial was conducted in fifteen patients treated for a total of 30 sinus randomly allotted into two groups. In patients of Group I, a triangular flap was performed, while in Group II modified triangular flap without anterior release was performed. Postoperative pain was scored by VAS and inflammation was recorded by VRS at 2, 4, 6 and 14 days. The facial temperature was recorded before and after sinus augmentation, at 2, 4, 6 day intervals for the first week and at 14 day, to check the course of healing. Results: In group I the pain intensity was recorded at 2 days after the surgery with a score of 38.67 ± 6.4 mm. Swelling was higher at 2 and 4 day, and it was absent at day 6. Facial temperature difference before and after the procedure was 3 (4.737 °C ± 0.37). In Group II the pain was lower than in Group I (p < 0,05). Swelling scored 2 on the first and second day, and it was reduced at day 4. After the second day the difference of temperature reduced significantly compared to day of surgery (0.77 °C), at 2 and 4 days no difference was registered. Conclusion: In conclusion based on the outcome of the present study, modified triangular flap can be used with success in sinus augmentation procedures and is to be preferred to trapezoidal flap.

The manufacturing method influences the properties of the produced components. This work investigates the influence of manufacturing methods such as fused filament fabrication (3D printing) and injection molding on water absorption, mechanical and thermal properties of the specimens produced from neat biobased poly(lactic acid) (PLA) polymer and poly(lactic acid)/wood composites. Acrylonitrile butadiene styrene (ABS) acts as the reference material due to its low water absorption and good functional properties. The printing layer thickness is one of the factors that affects the properties of a 3D printed specimen. The investigation includes two different layer thicknesses (0.2 mm and 0.3 mm) while maintaining uniform overall thickness of the specimens across two manufacturing methods. 3D printed specimens absorb significantly higher amounts of water than the injection molded specimens, and the increase in the layer thickness of the 3D printed specimens contributes to further increased water absorption. However, the swelling due to water absorption in 3D printed specimens decreases on increased layer thickness. Tensile, flexural and impact properties of all the specimens decrease after water absorption while the properties improve on decreasing the layer thickness. Higher porosity on increasing the layer thickness is the predominant factor. The results from dynamic mechanical analysis and microscopy validate the outcomes.

Introduction: Due to the great development of digital technology, through CAD (Computer - Aided Design) and CAM (Computer - Aided Manufacturing) systems, digital models could be used in orthodontic treatment planning decision-making, as there are numerous studies in the literature that support the validity of measurements of digital models of anterior teeth and the total coefficient of Bolton analysis. The aim of the study was to compare the average length value of the current upper and lower arches with that of a hypothetical nickel-titanium wire and the accuracy of the Bolton index measurement. In the present study, 138 dental casts were analyzed using Ortho3Shape software. Using the Ortho3Shape software, it was possible to measure the real and ideal lower arch lengths and, with regard to Bolton analysis, the values of the anterior and total Bolton coefficients. By comparing the values obtained with those of the study by A. Anand Kumar et al. using CBCT and plaster casts, the reliability of the measurements obtained with such CAD/CAM orthodontic software was evaluated. Considering the validity of digital measurements demonstrated by the studies and systematic reviews in the literature, it can be stated that CAD/CAM digital models can be a viable alternative to plaster models in the coming years, as they can facilitate model preservation and retrieval. For future studies and research, it would be preferable to use intra-oral scanners (IOS) in order to ensure greater accuracy, requiring only one step and ensuring a better outcome for the patient.

Aqueous Zinc ion batteries (ZIBs) possess significant potential in large energy storage systems due to their cost-effectiveness and environmental protection. However, the limited voltage window and poor reaction kinetics of the cathode material are still bottlenecks, restricting the further development of ZIBs. In this work, we rationally design Ni-doped V2O5@3D Ni core/shell composite on carbon cloth electrode (Ni-V2O5@3D Ni@CC) by growing Ni-V2O5 on the free-standing 3D Ni metal nanonets for high-voltage and high-capacity ZIBs. Impressively, the embedded Ni doping increases the interlayer spacing of V2O5, extending the working voltage and improving the Zn2+ kinetics reaction of the cathode materials, at the same time the 3D structure with high specific surface area and superior electronic conductivity benefits to fast Zn2+ transport. Consequently, the as-designed Ni-V2O5@3D Ni@CC cathodes can operate within a wide voltage window from 0.3 to 1.8 V vs. Zn/Zn2+ and deliver a high capacity of 270 mAh g-1 at a high current density of 0.8 A g-1. In addition, the reversible Zn2+ (de)-incorporation reaction mechanisms in the Ni-V2O5@3D Ni@CC cathodes are investigated by multiple characterization methods. As a result, we achieve a big step toward the practical applications of commercial ZIBs.

The decreasing width, increasing aspect ratio RDL presents significant challenges to design for reliability (DFR) of advanced package. Therefore, this paper proposes a ML based RDL modeling and simulation method. In the method, RDL is divided into blocks and subdivided into pixels of metal percentage, and the RDL is digitalized as tensors. Then, an ANN-based surrogate model is built and trained by a subset of tensors to predict the equivalent material properties of each block. Lastly, all blocks are transformed into elements for simulations. For validation, line bending simulations were conducted on an RDL, with the reaction force as accuracy indicator. The results show that neglecting layout impact causes critical errors as substrate thins. By the method, the reaction force error is 2.81% and the layout impact can accurately be considered with 200×200 elements. For application, the TCT maximum temperature state simulation was conducted on a CPU chip. The simulation indicates that for advanced package the maximum stress more likely occurs in RDL rather than bumps, both RDL and bumps are critical impacted by layouts, and RDL stress is also impacted by vias/bumps. The proposed method precisely concerns layout impacts with little resources, presents an opportunity of efficiency improvement.

The initial stability after implantology is paramount to the survival of the dental implant and the surface roughness of the implant plays a vital role in this regard. The characterisation of surface topography is a complicated branch of metrology, with a huge range of parameters available. Each parameter contributes significantly towards the survival and mechanical properties of 3D-printed specimens. The purpose of this paper is to experimentally investigate the effect of surface roughness of 3D-printed dental implants and 3D-printed dogbone tensile samples under areal height (Ra) parameters, amplitude parameters (average of ordinates), skewness (Rsk) parameters and mechanical properties. During the experiment, roughness values were analysed and the results showed that the skewness parameter demonstrated a minimum value of 0.596%. The 3D-printed dental implant recorded Ra with a 3.4 mm diameter at 43.23% and the 3D-printed dental implant with a 4.3 mm diameter at 26.18%. Samples with a complex geometry exhibited a higher roughness surface, which was the greatest difficulty of additive manufacturing when evaluating surface finish. The results show that when the ultimate tensile stress (UTS) decreases from 968.35 MPa to 955.25 MPa, Ra increases by 1.4% and when UTS increases to 961.18 MPa, Ra increases by 0.6%. When the cycle decreases from 262142 to 137433, Ra shows that less than a 90.74% increase in cycle is obtained. For 3D-printed dental implants, the higher the surface roughness, the lower the mechanical properties, ultimately leading to decreased implant life and poor performance.

Paclitaxel is a natural, highly lipophilic anti proliferative drug widely used in medicine. We have studied the release of tritium-labeled paclitaxel (³H-PTX) from matrices destined for the coating of vascular stents and produced by the electrospinning method from the solutions of polycaprolactone (PCL) with paclitaxel (PTX) in hexafluoisoropropanol (HFIP) and/or solutions of PCL with PTX and human serum albumin (HSA) in HFIP or HIFP-dimethyl sulphoxide (DMSO) blend. The release of PTX has been shown to depend on the solvent and the composition of electrospinning solution, as well as the composition of the surrounding medium, particularly the concentration of free PTX and PTX-binding biomolecules present in human serum. It was shown that 3D matrices can completely release PTX without weight loss. Two-phase PTX release from optimized 3D matrices was obtained: ~27% of PTX was released in the first day, another 8% were released over the next 26 days. Wherein ~2.8%, ~2.3%, and ~0.25% of PTX was released on day 3, 9, and 27, respectively. Considering PTX toxicity, the rate of its diffusion through the arterial wall, and the data obtained the minimum cytostatic dose of the drug in the arterial wall will be maintained for at least three months.

: Cardiac surgery (CS) with extracorporeal circulation (ECC), induces oxidative stress and systemic inflammatory response, which may seriously affect postoperative lung function. We aimed to test if high parenteral (200mg/kg/24h) perioperative (48h) doses of Vitamin C (VitC) may reduce the incidence and severity of postoperative pulmonary complications (PPC) in selected CS patients. Single centered, prospective, randomized, single-blinded, interventional study included 150 patients, assigned to control group A (n=75) and interventional group B (n=75). Group B intraoperatively received 1/4 of the planned daily Vit C dose (200mg/kg/24h), diluted in 10 ml of normal saline, divided into three parts, while Group A received an equal volume of normal saline at the same time frames. After 6 h from the first intraoperative dose, the following regimen was applied: Group B: 200 mg/kg/24h - 30 min i.v. infusion of VitC in 50 ml of normal saline, every 6h, for the next 48h, and Group A: 30 min i.v. infusion of an equal volume of normal saline every 6 hours, for the next 48h. Modified Kroenke’s score was used to determine the incidence and severity of PPC. The overall incidence of PPC was 36.7% and was significantly lower in Group B (13.3% v.s. 60.0%, p&lt;0.001). The severity of PPC was also significantly lower in Group B [1(1) v.s. 3(2), p&lt;0.001]. Besides, patients from Group B had significantly less damaged lungs and better postoperative renal function, shorter ICU stay, fewer ICU re-admissions, and lower hospital mortality. High parenteral daily VitC doses (200mg/kg/24h) given to selected CS patients for 48h after CS are safe and effective in reducing the incidence and severity of PPC. Further multicenter RCT is needed to confirm these results.

Whole genome duplication (WGD) or polyploidization can occur at the cellular, tissue, and organismal levels. At the cellular level, tetraploidization has been proposed as a driver of aneuploidy and genome instability, and correlates strongly with cancer progression, metastasis, and development of drugs resistance[1–6]. WGD is also a key developmental strategy for regulating cell size, metabolism, and cellular function[1,7–10]. In specific tissues, WGD is involved in normal development (e.g. organogenesis), tissue homeostasis, wound healing, and regeneration[10–17]. At the organismal level, WGD propels evolutionary processes such as adaptation[18], speciation[19], and crop domestication[20]. An essential strategy to further our understanding of the mechanisms promoting WGD and its effects is to compare isogenic strains that differ only in their ploidy. Caenorhabditis elegans (C. elegans) is emerging as an animal model for these comparisons, in part because relatively stable and fertile tetraploid strains can be produced rapidly from nearly any diploid strain[7]. Here we review the use of Caenorhabditis polyploids as tools to understand important developmental processes (e.g. sex determination, dosage compensation, and allometric relationships)[21–27] and cellular processes (e.g. cell cycle regulation, chromosome dynamics during meiosis)[28–32]. We also discuss how the unique characteristics of the C. elegans WGD model will enable significant advances in our understanding of mechanisms of polyploidization and its role in development and disease.

In this multicenter, retrospective study we evaluated the added value of magnetic resonance dispersion imaging (MRDI) to standard multiparametric MRI (mpMRI) for PCa detection. The study included 76 patients - 51 with clinically significant prostate cancer (csPCa), who underwent radical prostatectomy and had an mpMRI including dynamic contrast enhanced-MRI. Two radiologists performed three separate randomized scorings based on mpMRI, MRDI and mpMRI+MRDI. Radical prostatectomy histopathology was used as the reference standard. Imaging and histopathology were both scored according to the Prostate Imaging-Reporting and Data System V2.0 sector map. Sensitivity and specificity for PCa detection were evaluated for mpMRI, MRDI and mpMRI+MRDI. Inter- and intra-observer variability for both radiologists were evaluated using Cohen’s Kappa. On a per patient level, sensitivity for csPCa for radiologist 1 (R1) for mpMRI, MRDI and mpMRI+MRDI were 0.94, 0.82 and 0.94, respectively. For the second radiologist (R2) these were 0.78, 0.94 and 0.96. R1 detected 4% additional csPCa cases using MRDI compared to mpMRI and R2 detected 20% extra csPCa cases using MRDI. Inter-observer agreement was significant only for MRDI (Cohen’s kappa = 0.4250, p=0.004). The results of this study show the potential of MRDI to improve interobserver variability and the detection of csPCa.

To assess the impact of a deep learning (DL) denoising reconstruction algorithm applied to identical patient scans acquired with two different voxel dimensions, representing distinct spatial resolutions. This IRB approved prospective study was conducted at a tertiary pediatric center in compliance with the Health Insurance Portability and Accountability Act. We used a General Electric Signa Premier unit (GE Medical Systems, Milwaukee, WI) to acquire two DTI sequences of the left knee on each child at 3T: an in-plane 2.0 x 2.0 mm2 with section thickness of 3.0 mm and a 2 mm3 isovolumetric voxel, neither had an inter-section gap. We used a multi-band DTI acquisi-tion with fat-suppressed single-shot spin-echo echo-planar sequence (20 non-collinear directions; b-values of 0 and 600 sec/mm2). The MR vendor-provided a commercially available DL model applied with 75% noise reduction settings to same subject DTI sequences at different spatial res-olutions. We compared DTI tract metrics from both DL-reconstructed scans and non-denoised scans for femur and tibia, at each spatial resolution. Differences were evaluated using Wilcox-on-signed ranked test and Bland-Altman plots. When comparing DL versus non-denoised diffu-sion metrics in femur and tibia using the 2 mm x 2mm x 3 mm voxel dimension there were no significant differences between tract count (p = 0.1, p =0.14) tract volume (p = 0.14, p = 0.29), or tibial tract length (p=0.16); femur tract length exhibited a significant difference (p

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often causes severe viral pneumonia, especially among older individuals and those with underlying health conditions. The C57BL/6 mouse is widely used to develop mouse models of obesity, diabetes, hypertension, and immune disorders, conditions that are associated with increased risk of severe COVID-19. Although many studies using these mouse models have examined the pathogenicity of SARS-CoV-2, COVID-19 pathogenesis remains poorly understood. In vivo imaging analysis using two-photon excitation microscopy is useful for elucidating the pathology of COVID-19, providing pathological insights that are not available from conventional histological analysis. However, there is no reporter SARS-CoV-2 that demonstrates pathogenicity in C57BL/6 mice and emits sufficient light intensity for two-photon in vivo imaging. Here, we generated SARS-CoV-2 expressing the fluorescent protein Venus to facilitate in vivo pathological studies using C57BL/6 mouse models. We generated a mouse-adapted strain of SARS-CoV-2, by performing sequential lung-to-lung passages in BALB/c mice, followed by in C57BL/6 mice. We observed that the C57BL/6-adapted SARS-CoV-2 (named MASCV2-p25) replicated efficiently in the lungs of C57BL/6 mice, causing fatal pneumonia. Histopathologic analysis revealed severe inflammation and infiltration of immune cells in the lungs of MASCV2-p25-infected C57BL/6J mice, not unlike that observed in COVID-19 patients with severe pneumonia. Subsequently, we generated a mouse-adapted reporter SARS-CoV-2 (named MASCV-Venus-p9) by inserting the fluorescent gene Venus into MASCV2-p25, and sequential lung-to-lung passages in C57BL/6 mice. C57BL/6 mice infected with MASCV2-Venus-p9 exhibited severe pneumonia similar to that induced by MASCV2-p25. In addition, two-photon excitation microscopy of the lungs of the infected C57BL/6J mice showed that the infected cells emitted sufficient levels of fluorescence for easy observation. These findings suggest that MASCV2-Venus-p9 will be useful for two photon in vivo imaging studies of the pathogenesis of severe COVID-19 and for the development of therapeutic agents for severe pneumonia.

Video capsule endoscopy (VCE) is increasingly used to decrease the discomfort among patients owing to its small size. However, VCE has a major drawback of not having narrow band imaging (NBI) functionality. The current VCE has the traditional white light imaging (WLI) only, which has poor performance in the computer-aided detection (CAD) of different types of cancer compared with NBI. Specific cancers, such as esophageal cancer (EC), do not exhibit any early biomarkers, making their early detection difficult. In most cases, the symptoms are unnoticeable, and EC is diagnosed only in later stages, making its 5-year survival rate below 20% on an average. NBI filters provide particular wavelengths that increase the contrast and enhance certain features of the mucosa, thereby enabling early identification of EC. However, VCE does not have a slot for NBI functionality because its size cannot be increased. Hence, NBI image conversion from WLI can be achieved only in post-processing at present. In this study, a complete arithmetic assessment of the decorrelated color space was conducted to generate NBI images from WLI images for VCE of the esophagus. Three parameters, namely, structural similarity index metric (SSIM), entropy, and peak-signal-to-noise ratio (PSNR), were used to asses the simulated NBI images. Results show the good performance of the NBI image reproduction method, with SSIM, entropy difference, and PSNR values of 93.215%, 4.360, and 28.064 dB, respectively.

Development of supervised AI algorithms requires a large amount of labeled images. Image labelling is both time-consuming and expensive. Therefore, we explored the value of e-learning derived annotations for AI algorithm development in medical imaging. Methods We have developed an e-learning platform that involves image-based single click labelling as part of the educational learning process. Ten radiology residents, as part of their residency training, trained the recognition of pneumothorax on 1161 chest X-rays in posterior-anterior projection. Using this data, multiple AI algorithms for detecting pneumothorax were developed. Classification and localization performance of the models was tested on an independent internal testing dataset and on the public NIH ChestX-ray14 dataset. Results The AI models F1 scores on the internal and the NIH dataset were 0.87 and 0.44, respectively. Sensitivity was 0.85 and 0.80 for classification and specificity 0.96 and 0.48 for classification. F1 scores were 0.72 and 0.66, sensitivity 0.72 and 0.72. False positive rate was 0.36 and 0.32 for localisation. Conclusion Our results demonstrated that e-learning derived annotations are a valuable data source for algorithm development. Further work is needed to include additional parameters such as user performance, consensus of diagnosis, and quality control in the development pipeline.

Tumor vasculature proliferates rapidly, generally lacks pericyte coverage, and is uniquely frag-ile making it an attractive therapeutic target. A subset of small-molecule tubulin binding agents cause disaggregation of the endothelial cytoskeleton leading to enhanced vascular permeability generating increased interstitial pressure. The resulting vascular collapse and ischemia cause downstream hypoxia, ultimately leading to cell death and necrosis. Thus, local damage gener-ates massive amplification and tumor destruction. The tumor vasculature is readily accessed and potentially a common target irrespective of disease site in the body. Development of a therapeutic approach and particularly next generation agents benefits from effective non-invasive assays. Imaging technologies offer varying degrees of sophistication and ease of implementation. This review considers technological strengths and weaknesses with examples from our own laboratory. Methods reveal vascular extent and patency, as well as insights into tissue viability, proliferation and necrosis. Spatiotemporal resolution ranges from cellular mi-croscopy to single slice tomography and full three-dimensional views of whole tumors and measurements can be sufficiently rapid to reveal acute changes or long-term outcomes. Since imaging is non-invasive, each tumor may serve as its own control making investigations par-ticularly efficient and rigorous. The concept of tumor vascular disruption was proposed over 30 years ago and it remains an active area of research.

The superharmonic imaging of tissue has the potential for high spatial and contrast resolutions, compared to the fundamental and second harmonic imaging. For this technique, the spectral bandwidth of an ultrasound transducer is divided for transmission of ultrasound and reception of its superharmonics (i.e., higher than the second harmonic). Due to the spectral division for the transmission and reception, transmitted ultrasound energy is not sufficient to induce superharmonics in media without using contrast agents, and it is difficult that a transducer has a -6-dB fractional bandwidth of higher than 100%. For the superharmonic imaging of tissue, thus, multi-frequency array transducers are the best choice if available; transmit and receive elements are separate and have different center frequencies. However, the construction of a multi-frequency transducer for intravascular ultrasound (IVUS) imaging is particularly demanding because of its small size of less than 1 mm. Here, we report a recently developed dual-element focused IVUS transducer for the third harmonic imaging of tissue, which consists of a 35-MHz element for ultrasound transmission and a 105-MHz element for third harmonic reception. For high quality third harmonic imaging, both elements were fabricated to have the same focus at 2.5 mm. The results of tissue mimicking phantom tests demonstrated that the third harmonic images produced by the developed transducer had higher spatial resolution and deeper imaging depth than the fundamental images.

The forage fish, a crucial source of nutrition in developing countries, are unfortunately primarily used for fishmeal and aquafeed production for aquaculture that mainly serves consumers in developed countries. Industrial fish use leaves a meager portion of the catch for direct human consumption in the fish-producing countries, leading to inflated fish prices locally. Overfishing forage fish necessary to support the fish reduction industry disrupts the ecosystem, diminishes the catch of larger fish, such as mackerel, and marginalizes local artisanal fishermen. This article appraises roughly the financial and nutritional impacts of elevated fish prices on low-income consumers in forage fish-producing countries, drawing attention to the ethical implications of this situation. A hypothetical 10% boost in the annual supply of fresh forage fish to the current global supply of 5 million MT markets could save consumers hundreds of millions of US dollars globally, tens of mil-lions of US dollars nationally, and several dollars for a family while improving the nutrition of families that depend on forage fish. The numbers suggest that even a modest boost to the supply of forage fish in fresh fish markets could significantly benefit the fish-producing nations' consumers and the fish-producing nations. In some countries, such as South Africa, the orders of magnitude of these sums approach that of the entire local fish reduction industries' value. The increased fish prices could be considered involuntary subsidies by low-income consumers to the aquafeed and aquaculture industries. In summary, the reduction industry's and aquaculture's current use of captured forage fish warrants further scrutiny, as it inadvertently burdens disadvantaged societies financially and nutritionally. The article proposes alternative protein sources and cultivating non-carnivorous fish among several optional measures to ensure equitable distribution of forage fish resources.

Mycotoxins are secondary metabolites produced by filamentous fungi associated to a variety of acute and chronic foodborne diseases. Current toxicology studies mainly rely on monolayer cell cultures and animal models, which are undeniably affected by several limitations. To bridge the gap between the current in vitro toxicology approach and the in vivo predictivity of the data, we here investigated the cytotoxic effects induced by the mycotoxins sterigmatocystin (STE), ochratoxin A (OTA) and patulin (PAT) on different 2D and 3D cell cultures. We focused on human tumours (neuroblastoma SH-SY5Y cells, and epithelial breast cancer MDA-MB-213 cells) and healthy cells (bone marrow derived mesenchymal stem cells, BM-MSC, and umbilical vein endothelial cells, HUVECs). Cytotoxicity of STE, OTA, and PAT was determined after 24, 48 and 72 h of exposure by ATP assay in both culture models. 3D spheroids morphology was also analysed using the MATLAB-based open-source software AnaSP. Our results highlighted how each cell line and different culture models showed specific sensitivities, reinforcing the importance of using more complex models for toxicology studies and a multiple cell line approach for an improved and more comprehensive risk assessment.

The article reports on a patient who required a cranial protection system.Using additive manufacturing techniques and surgical planning with the help of bio-models, a patient-specific bone implant solution was proposed that allows aesthetic restoration of the affected area and provides an adequate level of protection. In addition, through a comparative analysis with finite elements, the mechanical response to external actions of the medical device, printed with two materials: polymethylmethacrylate (PMMA) and polyether-ether-ketone (PEEK), is simulated. The tested materials have recognized biocompatibility properties, but their costs on the market differ significantly. The results obtained demonstrate the similarities in the responses of both materials. It offers the possibility that low-income people can access these devices, guaranteeing adequate biomechanical safety, considering that PMMA is a much cheaper material than PEEK.

This study presents a novel semi-supervised deep learning method utilizing 3D TOF-MRA images for the detection of brain aneurysms, employing landmark-based techniques that mimic radiologist practices to enhance detection accuracy and efficiency.

Mapping building roof plane structures is an active research direction in urban-related studies, as understanding roof structure provides essential information for generating highly detailed 3D building models. Traditional deep learning models have been the main focus of most recent research endeavours aiming to extract pixel-based building roof plane areas from remote sensing imagery. However, significant challenges arise, such as delineating complex roof boundaries and invisible boundaries. Additionally, challenges during the post-processing phase, where pix-el-based building roof plane maps are vectorized, often result in polygons with irregular shapes. In order to address this issue, this study explores a state-of-the-art method for planar graph reconstruction applied to building roof plane extraction. We propose a framework for reconstructing regularized building roof plane structures using aerial imagery and cadastral information. Our framework employs a holistic edge classification architecture based on an attention-based neural network to detect corners and edges between them from aerial imagery. Our experiments focused on three distinct study areas characterized by different roof structure topologies: Stadsveld – 't Zwering neighbourhood and Oude Markt area, located in Enschede, The Netherlands, and the Lozenets district in Sofia, Bulgaria. The outcomes of our experiments revealed that a model trained with a combined dataset of two different study areas demonstrated superior performance, capable of delineating edges obscured by shadows or canopy. Our experiment in the Oude Markt area resulted in building roof plane delineation with an F-score value of 0.43 when the model trained on the combined dataset was used. In comparison, the model trained only on the Stadsveld – 't Zwering dataset achieved an F-score value of 0.37, and the model trained only on the Lozenets dataset achieved an F-score value of 0.32. The results from the developed approach are promising and can be used for 3D city modelling in different urban settings.

This paper presents a numerical study on the laser shock wave propagation in a 3D woven CFRP material by means of detailed and homogenized FE models. The aim of the study is to numerically characterize the shock wave response of the 3D woven CFRP in terms of back face velocity profiles and the induced damage and to investigate whether the detailed FE models could be replaced by homogenized FE models. The 3D woven geometry was designed using the TexGen software, while the numerical analyses were executed using the LS-Dyna explicit FE software. A high-strain rate behavior was considered for the matrix. The fiber bundles in the detailed models were modeled as a high fiber content unidirectional composite laminate, with its mechanical properties calculated by micromechanical equations. Both for the fiber bundles of the detailed model and the homogenized models a progressive damage material model was applied. The results of the detailed model reveal a considerable effect of material’s architecture on the shock wave propagation and the sensitivity of the back face velocity profile to the spot location. Consequently, the homogenized model is not capable of accurately simulating the shock wave response of the 3D woven composite. Moreover, the detailed predicts with high accuracy matrix cracking in the resin-rich areas and in the bundles as well as fiber failure. On the contrary, the homogenized model predicts matrix cracking at the same areas and no fiber failure.

Traditional lithium-ion batteries cannot meet the high flexibility and bendability requirements of modern flexible electronic devices due to the limitations of their electrode materials. Therefore, the development of high-performance flexible energy storage devices is of great significance for promoting flexible electronics. In recent years, one-dimensional flexible fiber lithium-ion batteries have been rapidly developed due to the advantages of high flexibility and bendability. However, it is still a big challenge to realize 1D flexible fiber lithium-ion batteries with excellent electro-chemical properties and good mechanical performance. In this work, a reduced graphene ox-ide-based printing ink is proposed to fabricate flexible Li4Ti5O12/graphene fiber electrodes through a 3D printing assembly strategy. It is noteworthy that the green reducing agent vitamin C was used to reduce graphene oxide in one step, which improved the conductivity of the fiber elec-trode. Furthermore, a 3D conductive network is constructed inside the fiber electrodes due to the high specific surface area of reduced graphene oxide, which enhances the electronic conductivity and ion mobility. The fiber electrode not only has good mechanical performance, but also has ex-cellent electrochemical properties. Equally important, the method is simple and efficient, and the working environment is flexible. It can precisely control the shape, size and structure of the one-dimensional fiber flexible electrode, which is of great significance for the development of fu-ture flexible electronic devices.

This paper proposes an algorithm for transmitting and reconstructing the estimated point cloud using temporally estimating a dynamic point cloud sequence. When a non-rigid 3D point cloud sequence (PCS) is input, the sequence is divided into groups of point cloud frames (PCF), and a key PCF is selected. After the 3D skeleton is predicted through 3D pose estimation, the motion of the skeleton is estimated by analyzing the joints and bones of the 3D skeleton. For the deformation of the non-rigid human PC, the 3D PC model is transformed into a mesh model, and the key PCF is rigged using the 3D skeleton. After deforming the key PCF into the target PCF utilizing the motion vector of the estimated skeleton, the residual PC between the motion compensation PCF and the target PCF is generated. If there is a key PCF, the motion vector of the target PCF, and a residual PC, the target PCF can be reconstructed. Just as compression is performed using pixel correlation between frames in a 2D video, this paper compresses 3D PCF by estimating the non-rigid 3D motion of a 3D object in a 3D PC. The proposed algorithm can be regarded as an extension of the 2D motion estimation of a rigid local region in a 2D plane to the 3D motion estimation of a non-rigid object (human) in 3D space. Experimental results show that the proposed method can successfully compress 3D PC sequences. If it is used together with a PC compression technique such as MPEG PCC (point cloud compression) in the future, a system with high compression efficiency may be configured.

Laser Direct Writing (LDW), also known as 3D multi-photon laser lithography of resins, is a promising technique for fabricating complex free-form elements, including micro-optical functional components. Regular organic or hybrid (organic-inorganic) resins are often used, with latter exhibiting better optical characteristics, as well as having the option to be heat-treated into inorganic glass-like structures, particularly useful for resilient micro-optics. While this work is a continuation of SZ2080™ calcination development , the Laser-Induced Damage Threshold (LIDT) of such sol-gel-derived glass micro-structures, particularly those that undergo heat treatment, has not been well-characterized. In this pilot study, we investigated the LIDT using the Series-on-One (S-on-1) protocol of functional micro-lenses produced via LDW and subsequently calcinated. Our results demonstrate that the LIDT can be significantly increased, even multiple times, by this approach, thus enhancing the resilience and usefulness of these free-form micro-optics. This work represents the first investigation in terms of LIDT into the impact of calcination on LDW produced sol-gel-derived glass micro-structures, and provides important insights for the development of robust micro-optical devices.

The Coronavirus disease 2019 (COVID-19) rapidly spread to over 180 countries and abruptly disrupted the production rates and supply chains worldwide. Since then, 3D printing also recognized as additive manufacturing (AM) and known to be a novel technique that uses layer-by-layer deposition of material to produce the intricate 3D geometry, has been engaged in reducing the distress caused by the outbreak. During the early stages of this pandemic, shortages of Personal Protection Equipment (PPE), including facemasks, shields, respirators, and other medical gears, were significantly answered by remotely 3D printing them. Amidst the growing testing requirements, the 3D printing emerged as a potential and fast solution manufacturing process to meet the production needs due to its flexibility, reliability, and rapid response capabilities. In the recent past, some of the other medical applications that have gained prominence in the scientific community include 3D printed ventilator splitters, device components, and patient-specific products. Regarding the non-medical applications, researchers have successfully developed contact-free devices to address the sanitary crisis in public places. This work aims to systematically review the applications of 3D printing or AM techniques that have been involved in producing various critical products essential to limit this deadly pandemic's progression.

The extrusion-based 3D concrete printing (3DCP) technology allows the fabrication of permanent formwork with intricate shapes, into which fresh concrete is cast to build structural members with complex geometry. This significantly enhances the geometric freedom of concrete structures without the use of expensive temporary formwork. In addition, with proper material choice for the permanent formwork, the load-bearing capacity and durability of the resulting structure can be improved. This paper investigates 3DCP of permanent formwork for reinforced concrete (RC) beam construction. A 3D-printable engineered geopolymer composite (3DP-EGC, or strain-hardening geopolymer composite, 3DP-SHGC) recently developed by the authors was used for fabrication of the permanent formwork. The 3DP-EGC exhibits strain-hardening behaviour under direct tension. Two different printing patterns were used for the soffit of the permanent formwork to investigate the effect of this parameter on the flexural performance of RC beams. A conventionally mould-cast RC beam was also prepared as the control beam for comparison purposes. The results showed that the RC beams constructed using the 3DP-EGC permanent formwork exhibited superior flexural performance to the control beam. Such beams yielded significantly higher cracking load (up to 43%), deflection at ultimate load (up to 60%), ductility index (50%) and absorbed energy (up to 107%) than those of the control beam. The ultimate load was comparable with or slightly higher than that of the control beam. Furthermore, the printing pattern at the soffit of the permanent formwork was found to have a significant influence on the flexural performance of the RC beams.

In surveying engineering tasks, close-range photogrammetry belongs to leading technology considering different aspects like the achievable accuracy, availability of hardware and software, accessibility to measured objects, or the economy. Hence, constant studies on photogrammetric data processing are desirable. Especially in industrial applications, the control points for close-range photogrammetry are usually measured using total stations. In the case of small objects, more precise positions of control points can be obtained by deploying and adjusting a three-dimensional linear network set up on the object. The article analyzes the accuracy of the proposed method, based on the measurement of the linear network using a tape with a precision of ±1 mm. The experiment shows that the adjusted positions of the network control points can be determined with high, one-millimeter accuracy. The photogrammetric 3D model derived referring to such control points and stereo-images captured with a non-metric camera is also characterized by the highest possible precision, which qualifies the presented method to accurate measurements used in surveying engineering. The authors prove that the distance between two randomly optional points derived from the 3D model of a dimensioned object is equal to the actual distance measured directly on it with one-millimeter accuracy.

Seismic travel time tomography using surface waves is an effective tool for three-dimensional crustal imaging. Historically, these surface waves are the result of active seismic sources or earthquakes. More recently, however, also surface waves retrieved through the application of seismic interferometry are exploited. Conventionally, two-step inversion algorithms are employed to solve the tomographic inverse problem. That is, a first inversion results in frequency-dependent, two-dimensional maps of phase velocity, which then serve as input for a series of independent, one-dimensional frequency-to-depth inversions. As such, a two-dimensional grid of localized depth-dependent velocity profiles are obtained. Stitching these separate profiles together subsequently yields a three-dimensional velocity model. Relatively recently, a one-step three-dimensional non-linear tomographic algorithm has been proposed. The algorithm is rooted in a Bayesian framework using Markov chains with reversible jumps, and is referred to as transdimensional tomography. Specifically, the three-dimensional velocity field is parameterized by means of a polyhedral Voronoi tessellation. In this study, we investigate the potential of this algorithm for the purpose of recovering the three-dimensional surface-wave-velocity structure from ambient noise recorded on and around the Reykjanes Peninsula, southwest Iceland. To that end, we design a number of synthetic tests that take into account the station configuration of the Reykjanes seismic network. We find that the algorithm is able to recover the 3D velocity structure at various scales in areas where station density is high. In addition, we find that the standard deviation on the recovered velocities is low in those regions. At the same time, the velocity structure is less well recovered in parts of the peninsula sampled by fewer stations. This implies that the algorithm successfully adapts model resolution to the density of rays. Also, it adapts model resolution to the amount of noise on the travel times. Because the algorithm is computationally demanding, we modify the algorithm such that computational costs are reduced while sufficiently preserving non-linearity. We conclude that the algorithm can now be applied adequately to travel times extracted from (time-averaged) station-station cross correlations by the Reykjanes seismic network.

As the first time, 0D-1D-3D and fully 3D steady-state aero-thermo-fluid simulations of a structural oil-to-air Fan Outlet Guide Vane Cooler (FOGVC) in a jet engine are presented. Using the commercial softwares Ansys Fluent, the thermo-mechanical module of Ansys and the 1D fluid solver Flownex, 5 simulation types (3D fully conjugate heat transfer with and without a thin wall model, 3D with a thin wall model, 1D-3D coupled, 1D and 0D) corresponding to 4 levels of simplification in 3 possible domains (oil, oil-metal and oil-metal-air) have been compared to provide selection criteria when a determined level of accuracy in the simulations without prohibited computational times is desired. The methodologies are applied to two different oil internal cavities: an inverted U with rectangular cross section and a coil internal cavity with a circular cross section. The obtained results show that depending on the scope of the research (outlet oil temperature, dissipated heat rate or oil pressure drop) and the accuracy of the results, one method or the other may be used. Experimental data would be needed to validate the numerical results by all employed methodologies and geometries.

Tuning fork gyroscopes (TFGs) are promising for potential high-precision applications. This work proposes and experimentally demonstrates a novel high-Q dual mass tuning fork microelectro-mechanical system (MEMS) gyroscope utilizing three-dimensional (3D) packaging techniques. Except for two symmetrically-decoupled proof masses (PM) with synchronization structures, a symmetrically-decoupled lever structure is designed to force the antiparallel, antiphase drive-mode motion and basically eliminate the low-frequency spurious modes. The thermoelastic damping (TED) and anchor loss are greatly reduced by the linearly-coupled, momentum- and torque-balanced antiphase sense mode. Besides, a novel 3D packaging technique is used to realize high Q-factors. A composite substrate encapsulation cap, fabricated by through-silicon-via (TSV) and glass-in-silicon (GIS) reflow processes, is anodically bonded to the sensing structures at wafer scales. A self-developed control circuit is adopted to realize loop control and characterize gyro-scope performances. It is shown that a high-reliability electrical connection together with a high-air-impermeability package can be fulfilled with this 3D packaging technique. Furthermore, the Q-factors of the drive and sense modes reach up to 51947 and 49249, respectively. This TFG realizes a wide measurement range of ±1800° /s and a high resolution of 0.1° /s with a scale-factor nonlinearity 720 ppm after automatic mode-matching. Besides, the long-term zero-rate output (ZRO) drift can be effectively suppressed by temperature compensation, inducing a small angle random walk (ARW) of 0.923°/√h and a low bias instability (BI) of 9.270°/h.

Cardiovascular-related diseases are one of the leading causes of death worldwide. An understanding of heart movement based on images plays a vital role in assisting the procedure in the postoperative and postoperative processes. In particular, if the shape information can be provided in real-time using the electrocardiogram(ECG) signal using this information, the heart’s movement information can be used for cardiovascular analysis and imaging guides during surgery. In this paper, we propose creating a 3D+t cardiac coronary artery model that is rendered in real-time according to the ECG signal. Hierarchical cage-based deformation modeling is used to generate mesh deformation used during the procedure according to the ECG signal. We match the blood vessel’s lumen obtained from the ECG-gated 3D+t CT angiography taken at the multiple cardiac phases to derive the optimal deformation. Splines for 3D deformation control points were used to continuously represent the obtained deformation at the multi-view according to the ECG signal. To verify the proposed method, we compared the manually segmented lumen and results of the proposed method for eight patients. The average distance and dice coefficient between the two models was 0.543mm and 0.735, respectively. The required time for registration of the 3D coronary artery model is 23.53 seconds/model. rendering speed to derive the model according to the ECG signal after generating the 3D+t model is faster than 120 FPS.

Dynamic thermogravimetric (TG) analysis under nitrogen environment was used to understand the thermal decomposition process of 3D printing filaments made of wood-filled polylactic acid (PLA)/starch blend. The characteristic temperatures and apparent activation energy (AAE) of the filaments with various starch contents were calculated with well-known kinetic models by Friedman, Flynn-Wall-Ozawa, Coats-Redfern and Kissinger. With the increased starch content in the filament, the onset thermal decomposition temperatures of the filaments decreased gradually from 272.4 to 155.1°C. The thermal degradation degree became smaller, and the transitional temperature interval became larger with increased starch proportion. The AAE values of the three types of filaments with different starch ratios varied between 97 kJ/mol and 114 kJ/mol, depending on material composition and method of calculation. The improved understanding of thermal decomposition behavior of PLA-starch-wood composites can help develop more biodegradable PLA/starch-based filaments for 3D printing.

Background: In susceptible hosts, SARS-CoV2 induced hyperinflammation accounts for an increased mortality. The search of adjuvant immunomodulatory therapies has been ongoing ever since the pandemic outbreak. Aim: Our purpose was to evaluate the efficacy of cyclosporin A (CsA) as add-on therapy to standard of care in patients with severe COVID-19 pneumonia. Methods: We conducted a randomized clinical trial in patients admitted to 8 Spanish Tertiary Hospitals. Patients were stratified into two severity categories and randomized 1:1 to receive a high dose corticosteroid-based standard therapy with or without CsA. The primary endpoint was FiO2 recovery by day 12 without relapses. Results: 109 patients were included and 98 randomized: 51 of them were assigned to CsA+SoC group and 47 to Standard of Care (SoC). 96/98 of them were included in the Intention to Treat population. 35 (68.6%) patients from CsA+SoC group and 32 (71,1%) patients from SoC group reached the primary endpoint in the ITT analysis. No differences were found after stratification into age groups, severity level at admission or the combination of both. Overall, time to FiO2 normalization was 7.4 days vs 7.9 days in the experimental and control groups, respectively. Global mortality was 8.2%. Severe adverse events were uncommon and equally distributed between arms. Conclusion: Addition of CsA did not show differences over a high-dose corticosteroids-based treatment in the clinical course of included patients. A better identification of candidates who will benefit from receiving immunomodulatory drugs is necessary in future studies.

(1) Background: “Zero-dose” (ZD) refers to a child not receiving any doses of the pentavalent (diphtheria-tetanus-pertussis-Haemophilus influenzae type b (Hib)-Hepatitis B) vaccine in the routine national immunization schedule. These children are vulnerable to vaccine-preventable diseases (VPDs), and are often already disadvantaged due to poverty, conflict, and lack of access to basic health services. The Luambo health district (HD) is one of the 26 HDs in the Kasai Central Province and has the largest number of ZD children. This study was conducted to examine the factors associated with ZD status in the Luambo HD; (2) Methods: We conducted a mixed study of children aged 12-23 months in the Luambo HD in the Kasai Central Province; (3) Results: A total of 445 children aged 12-23 months were included in the study, including 89 cases and 356 controls. Correlates of zero dose (ZD) status in children aged 12-23 months were mothers who were not receiving Antenatal Care (ANC), of not knowing any VPD, the fact of the children being born in Angola and the fact of the children being born at home. In addition, the perceptions of children’s parents influenced child immunization; (4) Conclusions: Missing ANC services during pregnancy leads to home delivery with consequences being lack of knowledge on childhood’s VPD and subsequently children not being vaccinated.

Conformal radiotherapy is a primary treatment in head and neck cancer, which putative adverse effects depend on relatively low doses of radiation delivered to increased volumes of normal tissues. Systemic effects of such treatment include radiation-induced changes in serum lipid profile, yet dose- and volume-dependence of these changes remain to be established. Here we analyzed levels of choline-containing phospholipids in serum samples collected consecutively during the radiotherapy used as the only treatment modality. The LC-MS approach applied in the study enabled the detection and quantitation of 151 phospholipids, including (lyso)phosphatidylcholines and sphingomyelins. No statistically significant differences were found in the pre-treatment samples from patients with different location and stage of cancer. To compensate for potential differences between schemes of radiotherapy the biologically effective doses were calculated and used in the search of correlations with specific lipid levels. We found that the levels of several phospholipids depended on the maximum dose delivered to the gross tumor volume and total radiation energy absorbed by the patient’s body. Increased doses correlated with increased levels of sphingomyelins and reduced levels of phosphatidylcholines. Noteworthy, serum phospholipid levels were associated mainly with volumes of normal tissues irradiated with relatively low doses (i.e., total accumulated dose 20 Gy), which indicated the importance of such effects on the systemic response of the patient’s organism to IMRT.

Background There is anecdotal evidence that ivermectin may decrease the frequency of seizures in Onchocerca volvulus-infected persons with epilepsy (PWE). Methods In October 2017, a 12-month clinical trial was initiated in rural Democratic Republic of Congo. PWE with onchocerciasis-associated epilepsy with ≥2 seizures/month were randomly allocated to receive over a one year period, ivermectin once or thrice (group 1), while other onchocerciasis-infected PWE (OIPWE) were randomized to ivermectin twice or thrice (group 2). All participants also received anti-epileptic drugs (AED). Study outcomes included seizure freedom during the last four months (primary endpoint), decrease in microfilarial density, and occurrence of adverse events. A multiple logistic regression model was used to evaluate the primary outcome. Results Of the 197 OIPWE enrolled, 100 were randomized to receive ivermectin thrice, 52 twice, and 45 once. In an intent-to-treat combined analysis of data from group 1 and 2, the probability to become seizure-free for OIPWE treated with ivermectin twice per year was significantly higher than in those treated once (OR: 5.087, 95% CI: 1.378-19.749; p=0.018) and individuals who received ivermectin twice had a 4.471 (95% CI: 0.944-6.769, p=0.075) times higher odds of seizure freedom than those received ivermectin once per year. Absence of microfilariae during the last 4 months was associated with a higher probability of seizure freedom (p=0.027). Conclusions Increasing the number of ivermectin treatments per year was found to suppress both microfilarial density and seizure frequency in OIPWE, suggesting that O. volvulus infection plays an etiological role in causing seizures. Registration: www.clinicaltrials.gov; NCT03852303

Leaf photosynthetic pigments play a crucial role in evaluating nutritional elements and physiological states. In facility agriculture, it is vital to obtain rapidly and accurately the pigment content and distribution of leaves to ensure precise water and fertilizer management. In our research, we utilized chlorophyll a (Chla), chlorophyll b (Chlb), chlorophyll (Chll), and carotenoid (Caro) as indicators to study the variations in leaf position of Lycopersicon esculentum Mill. Under 10 nitrogen concentration applications, a total of 2610 leaves (435 samples) were collected using visible-near infrared hyperspectral imaging (VNIR-HSI). In this study, a "coarse-fine" screening strategy was proposed by using competitive adaptive reweighted sampling (CARS) and iteratively retained informative variable (IRIV) algorithm to extract characteristic wavelengths. Finally, simultaneous and quantitative models were established using partial least squares regression (PLSR). The CARS-IRIV-PLSR was used to create models to achieve a better prediction effect. The coefficient determination (R2), root mean square error (RMSE), and ratio performance deviation (RPD) were predicted to be 0.8240, 1.43, 2.38 for Chla, 0.8391, 0.53, 2.49 for Chlb, 0.7899, 2.24, 2.18 for Chll, and 0.7577, 0.27, 2.03 for Caro, respectively. The combination of these models with the pseudo-color image allowed for a visual inversion of the content and distribution of pigment. These findings have important implications for guiding pigment distribution, nutrient diagnosis, and fertilization decisions in plant growth management.

Fibroblast activation protein (FAP) is a membrane-tethered serine protease overexpressed in the reactive stromal fibroblasts of &gt; 90% human carcinomas, which makes it a promising target for developing radiopharmaceuticals for imaging and therapy of carcinomas. Here, we synthesized two novel (R)-pyrrolidin-2-yl-boronic acid-based FAP-targeted ligands; SB02055 (DOTA-conjugated (R)-(1-((6-(3-(piperazin-1-yl)propoxy)quinoline-4-carbonyl)glycyl)pyrrolidin-2-yl)boronic acid) and SB04028 (DOTA-conjugated ((R)-1-((6-(3-(piperazin-1-yl)propoxy)quinoline-4-carbonyl)-D-alanyl)pyrrolidin-2-yl)boronic acid). natGa- and 68Ga-complexes of both ligands were evaluated in preclinical studies and compared to previously reported natGa/68Ga-complexed PNT6555. Enzymatic assays showed that FAP binding affinities (IC50) of natGa-SB02055, natGa-SB04028 and natGa-PNT6555 were 0.41±0.06, 13.9±1.29 and 78.1±4.59 nM, respectively. PET imaging and biodistribution studies in HEK293T:hFAP tumor-bearing mice showed that while [68Ga]Ga-SB02055 presented with a nominal tumor uptake (1.08±0.37 %ID/g), [68Ga]Ga-SB04028 demonstrated clear tumor visualization with ~1.5-fold higher tumor uptake (10.1±0.42 %ID/g) compared to [68Ga]Ga-PNT6555 (6.38±0.45 %ID/g). High accumulation in the bladder indicated renal excretion of all three tracers. [68Ga]Ga-SB04028 displayed low background level uptake in most normal organs, and comparable to [68Ga]Ga-PNT6555. However, since its tumor uptake was considerably higher than [68Ga]Ga-PNT6555, the corresponding tumor-to-organ uptake ratios for [68Ga]Ga-SB04028 were also significantly greater than [68Ga]Ga-PNT6555. Our data demonstrate that (R)-(((quinoline-4-carbonyl)-D-alanyl)pyrrolidin-2-yl)boronic acid is a promising pharmacophore for the design of FAP-targeted radiopharmaceuticals for cancer imaging and radioligand therapy.

Background: Painful spinal bone metastases (PSBMs) patients regularly receive palliative radiation therapy (RT) with response rates in about 2 of 3 patients. In this exploratory study, we evaluated the value of machine learning (ML) models based on radiomic, semantic and clinical features to predict complete pain response. Methods: Gross tumour volumes (GTV) and clinical target volumes (CTV) of 261 PSBMs were segmented on planning computed tomography (CT) scans. Radiomic, semantic and clinical features were collected for all patients. Random forest (RFC) and support vector machine (SVM) classifiers were compared using repeated nested cross-validation.Results: The best radiomic classifier was trained on CTV with an area under the receiver-operator curve (AUROC) of 0.62 ± 0.01 (RFC; 95% confidence interval). The semantic model achieved a comparable AUROC of 0.63 ± 0.01 (RFC), significantly below the clinical model (SVM, AUROC: 0.80 ± 0.01); and slightly lower than the spinal instability neoplastic score (SINS; LR, AUROC: 0.65 ± 0.01). A combined model did not improve performance (AUROC: 0,74 ± 0,01).Conclusions: We could demonstrate that radiomic and semantic analyses of planning CTs allowed for limited prediction of therapy response to palliative RT. ML predictions based on established clinical parameters achieved the best results.

Background: In March 2020, a COVID-19 outbreak associated with the Falles Festival in Borriana, Spain, led to significant infections. Methods: In June 2022, we conducted a cross-sectional follow-up study of 473 socially engaged adults aged 18 to 64, examining the cumulative experience after SARS-CoV-2 infection and vaccination responses. Data included demographic details, lifestyle habits, medical history, infection records, and vaccinations from a population-based vaccine registry. Blood samples were analyzed for SARS-CoV-2 antibodies and cellular immunity. We employed a doubly robust inverse weighted probability analysis to estimate the booster vaccine dose's impact on long COVID prevalence and symptom count. Results: 28.1% of participants met the WHO criteria for long COVID, with older individuals showing higher rates. Not complying with long COVID criteria associated with factors including O blood group, higher occupational status, physical activity, three vaccine doses, strong SARS-CoV-2-S-reactive IFNγ‐producing‐CD8+ response, and infection during the Omicron period. Conversely, increased age, high or low social activity, underlying health conditions, a severe initial COVID episode, and reinfection associated with higher long COVID likelihood. A booster dose, compared to one or two doses, reduced long COVID risk by 74% (95% CI: 56.4% to 91.7%) and symptom count by 55.2% (95% CI: 31.6% to 78.7%). Conclusion: Long COVID was prevalent in a significant portion of those who contracted COVID-19, underscoring the need for sustained follow-up and therapeutic strategies. Vaccinations, notably the booster dose, had a substantial beneficial effect on long-term infection outcomes, affirming the vaccination’s role in mitigating SARS-CoV-2 infection consequences.

Current COVID-19 vaccines can effectively reduce disease severity and hospitalisation; however, they are not considerably effective in preventing infection and transmission. In this context, mucosal vaccines are pertinent to prevent SARS-CoV-2 infection and spread. In this study, we generated a replication-competent recombinant chimeric influenza A virus (IAV) expressing the receptor-binding domain (RBD) of SARS-CoV-2 prototype in the C-terminus of the neuraminidase (NA) of A/Puerto Rico/08/1934 H1N1 (PR8). The remaining seven segments from A/WSN/1933 H1N1 (WSN) were named PR8NARBD/WSN. We observed that the recombinant virus with the WSN backbone demonstrated improved expression of NA and RBD. A single intranasal dose of PR8NARBD/WSN in mice generated robust mucosal immunity, neutralising antibodies, cellular immunity, and tissue-resident memory T cells specific to SARS-CoV-2 and IAV. Importantly, immunisation with PR8NARBD/WSN viruses effectively protected mice against lethal challenges with H1N1, H3N2 IAV, and SARS-CoV-2 Beta variant and significantly reduced lung viral loads. Overall, our research demonstrates the promising potential of PR8NARBD/WSN as an attractive vaccine against emerging SARS-CoV-2 variants and influenza A virus infections.

Two antimicrobial agents such as silver nanoparticles (AgNPs) and titanium dioxide (TiO2) have been formulated with natural polysaccharides (chitosan or alginate) to develop innovative inks for the rapid, customizable, and extremely accurate manufacturing of 3D printed scaffolds useful as dressings in the treatment of infected skin wounds. Suitable chemical-physical properties for the applicability of these innovative devices were demonstrated through the evaluation of water content (88-93%), mechanical strength (Young’s modulus 0.23-0.6 MPa), elasticity, and morphology. The antimicrobial tests performed against Staphylococcus Aureus and Pseudomonas Aeruginosa demonstrated the antimicrobial activities against Gram+ and Gram– bacteria of AgNPs and TiO2 agents embedded in the CH or ALG macroporous 3D hydrogels (AgNPs MIC starting from 5 µg/ml). The biocompatibility of chitosan was widely demonstrated by cell viability tests and was higher than that observed for alginate. Constructs containing AgNPs at 10 µg/ml concentration level did not significantly alter cell viability as well as the presence of titanium dioxide; cytotoxicity towards human fibroblasts was observed starting with AgNPs concentration of 100 µg/ml. In conclusions, the 3D printed dressings here developed own the features to be cheap, highly defined, easy to be manufactured and further applied in personalized antimicrobial medicine applications.

The rapid development of Deep Learning brought novel methodologies for 3D Object Detection using LiDAR sensing technology. These improvements in precision and inference speed performances lead to notable high performance and real-time inference, which is especially important for self-driving purposes. However, the developments carried by these approaches overwhelm the research process in this area since new methods, new technologies, and software versions lead to different project necessities, specifications and requirements. Moreover, the improvements brought by the new methods may be due to improvements in newer versions of deep learning frameworks and not just the novelty and innovation of the model architecture. Thus, it became crucial to create a framework with the same software versions, specifications and requirements that accommodate all these methodologies and allow the easy introduction of new methods and models. A framework is proposed that abstracts the implementation, reusing and building of novel methods and models. The main idea is to facilitate the representation of state-of-the-art (SoA) approaches and simultaneously encourage the implementation of new approaches by reusing, improving and innovating modules in the proposed framework, which has the same software specifications to allow a fair comparison. This makes it possible to determine if the key innovation approach outperforms the current SoA by comparing models in a framework with the same software specifications and requirements.

This study aimed to develop chitosan-based apigenin spray dried solid dispersion using 1:1,1:1.5,1:2 w/w ratios. The results of process yield and drug assay were found to be (87.5%, 94.2%, and 95.86%), (95.2 ±1.34%), (99.5 ±0.85%), and (97.6 ±2.42%), respectively, for AC1, AC2, and AC3. Flow properties indicate the free flow of powders. FTIR revealed compatibility among chitosan and apigenin, and DSC and XRD showed prepared solid dispersion was on a molecular level and available in amorphous. In contrast, SEM images reflect irregular block and near-spherical shape elongated particles in the selected AC2. The antimicrobial examination reflects that AC2 was more effective against Gram-positive, negative, and fungal strains. AC2 SDSDs has more anti-oxidant property compared to pure flavonoid (AGN). Anti-proliferative activity against A549 lung cancer cell lines showed better anti-cancer activity by AC2 SDSDs. The selected AC2 SDSD filled in a 3D shell pill and further characterized for 3D shell pill for dissolution profiles and stability studies. The product has sustained release and similar release profiles after three months of storage. The findings suggest that the AC2 SDSDs may be a promising candidate for further development as a 3D printed drug delivery system for treating multiple disease conditions using model flavonoid- apigenin.

Emerging pollutants as pharmaceuticals have been focusing international attention for few decades. Ciprofloxacin (CIP) is a common drug widely found in effluents from hospitals, industrial and different wastewater treatment plants, as well as rivers. In this work, the lab-scale 3D-BER system was established, and more than 90% of the antibiotic CIP removal from the Low C/N wastewater. Best results were obtained with current intensity, and different C/N ratio significantly improve the removal of CIP and nitrates, when the ideal conditions were; C/N = 1.5-3.5, pH =7.0-7.5, and I = 60 mA. The highest removal efficiency of CIP = 94.20 %, NO3--N= 95.53 % and total nitrogen (TN) = 84.27 %, respectively. In this novel system, the autotrophic-heterotrophic denitrifying bacteria played vital role for the removal of CIP and enhanced denitrification process. Thus, autotrophic denitrifying bacteria uses CO2 and H2 as carbon sources to reduce nitrates to N2. This system has the assortment and prosperous community revealed at the current intensity of 60 mA, and the analysis of bacterial community structure in effluent samples fluctuates under different condition of C/N ratios. According to the results of LC-MS/MS analysis, the intermediate products were proposed after efficient biodegradation of CIP. Microbial community on biodegrading was mostly found at phylum, and class level was dominantly responsible for the NO3--N and biodegradation of CIP. This work can provide some new insights towards the biodegradation of CIP and the efficient removal of nitrates from low C/N wastewater treatment by the novel 3D-BER system.

The active debate about the processes governing the organic-rich sediment deposition generally involves the relative roles of elevated primary productivity and enhanced preservation related to anoxia. However, other less spotlighted factors could have a strong impact on such deposits: e.g. residence time into the water column (bathymetry), sedimentation rate, transport behavior of organo-mineral floccules on the sea floor. They are all strongly interrelated and may be obscured in the current conceptual models inspired from most representative modern analogues (i.e. upwelling zones and stratified basins). To improve our comprehension of organic matter distribution and heterogeneities, we conducted a sensitivity analysis on the processes involved in organic matter production and preservation which have been simulated within a 3D stratigraphic forward model. The Lower-Middle Toarcian of the Paris Basin was chosen as a case study as it represents one of the best documented example of marine organic matter accumulation. The relative influence of the critical parameters (bathymetry, diffusive transport, oxygen mixing rate and primary production) on the output parameters (Total Organic Carbon, and oxygen level), determined performing a Global Sensitivity Analysis, shows that, in the context of a shallow epicontinental basin, a moderate primary productivity (> 175 gC.m^-².yr^-1) can led to local anoxia and organic matter accumulation. We argue that, regarding all the processes involved, the presence and distribution of organic-rich intervals is linked as a first-order parameter to the morphology of the basin (e.g. ramp slope, bottom topography). These interpretations are supported by very specific ranges of critical parameters which allowed to obtain output parameter values in accordance with the data. This quantitative approach and its conclusions open new perspectives about the understanding of global distribution and preservation of organic-rich sediments.

Gliomas are common primary central nervous system (CNS) tumours which are often very difficult to diagnose, stage and manage because of their heterogeneity and molecular aberrations. The notable hallmark of gliomas is integrated genome mutations and methylome that correlates with distinctive patterns of transcription that potentiates glioma heterogeneity, angiogenesis and ultimately poor prognosis. The World Health Organization (WHO) has decided to reclassify gliomas based on molecular markers rather than the traditional anatomical basis; use of Nuclear Medicine techniques e.g. SPECT/PET and Magnetic Resonance Imaging (MRI) techniques based on molecular markers is set to become the future gold standards. This has led to the investigations on potential for the use of non-invasive imaging techniques such as [68Ga]68Ga-RGD positron emission tomography (PET) to be utilised routinely in clinical practice based on angiogenic markers and also the potential to add information that may assist in drug-design and therapeutic decision making. This review aims to provide an overview of the basis of recent advances in glioma imaging using molecular targeting with positron emission tomography and SPECT imaging, as well as the role in patient management i.e. diagnosis, staging, recurrence detection etc.

Spatial-structured longitudinal light beams are optical fields sculpted in three-dimensional (3D) space by diffractive optical elements. These beams have been recently suggested for use in im-proving several imaging capabilities, such as 3D imaging, enhancing image resolution, engineering the depth of field, and sectioning 3D scenes. All these imaging tasks are performed using coded aperture correlation holography systems. Each system designed for a specific application is characterized by a point spread function of a different spatial-structured longitudinal light beam. This article reviews the topic of applying certain structured light beams for optical imaging.

Hallux valgus deformity (HVD) involves subluxation of the first metatarsophalangeal joint. While HVD is primarily considered a forefoot condition, midfoot instability may play a significant role in its development and severity. Therefore, this review had a particular focus on understanding midfoot instability based upon weightbearing imaging assessments of the TMT joint. This review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched five databases for studies on midfoot instability in HVD patients. Severity of HVD was defined by hallux valgus angle (HVA) and distal metatarsal articular angle (DMAA). Data was extracted, and articles were graded using the Methodological Index for Non-Randomized Studies (MINORS). Of 547 initially retrieved articles, 23 met inclusion criteria. Patients with HVD showed higher HVA and DMAA on weight-bearing radiographs (WBRG) and weight-bearing computed tomography (WBCT) compared to healthy individuals. Midfoot instability was assessed through intermetatarsal angle (IMA) and tarsometatarsal angle (TMT angle). Patients with HVD exhibited greater IMA and TMT angles on both WBRG and WBCT. This review highlights the importance of weight-bearing imaging assessments for midfoot instability in HVD. IMA and TMT angles can differentiate between healthy individuals and HVD patients, emphasizing the significance of midfoot assessment in understanding HVD pathology.

Historically, the evaluation and assessment of the clinical response to treatment for canine back pain is subjective and relies on owner and clinician assessment of pain. This study evaluated the use of sequential infrared thermal images as a measure of the response of canine patients with back pain to a prescribed series of photobiomodulation therapy (PBMT) treatments. Qualifying participants had histories of pain and dysfunction associated with spinal osteoarthritis or intervertebral disk disease, or of non-specific uni- or bilateral back pain along the paravertebral epaxial muscles. Each patient was initially thermally imaged prior to PBMT treatment and then received multiple PBMT treatments delivered to the appropriate spinal area on days 1, 2, 3, and 4. Participants were reimaged on day 7. Thermal images provided an objective measure of superficial temperature changes over the area of PBMT treatment of each patient after the PBMT regimen. The temperature correlated with statistically significant changes in Colorado State University Canine Chronic Pain Scale scoring (CPS) and owner assessment using the Canine Brief Pain Inventory (CBPI), which includes a Pain Severity Score (PSS) and Pain Interference Score (PIS). The correlation of objective thermal imaging data with more subjective outcome measures suggests thermal imaging may be a valuable additional tool in monitoring therapy outcome.

Fatigue cracks in a wide array of industrial components and structures pose a significant threat to their integrity. Detecting fatigue cracks using ultrasonic inspection techniques is a widespread activity for economic reasons but there are limitations to the techniques due to the morphology of fatigue cracks. In addition to detection there is a need to measure the size of the cracks which are often within the volume of the material. Ultrasonic techniques are well-suited to look inside the volume of the material but achieving sufficient sensitivity to the tip of the cracks in particular is practically difficult. Without an accurate knowledge of where the tip of the crack lies there can be significant uncertainty in sizing measurements. Machine Learning (ML) techniques are being developed to aid in the inspection and monitoring tasks but presenting the ultrasonic data in a suitable way for machine learning is very important. This paper presents a new approach to condition the ultrasonic data for machine learning settings so that they can be used effectively and confidently to detect and size fatigue cracks. The new approach, using images termed parameter-spaces, will also aid in conventional inspections as they are able to give information to human operators as to the existence or not of these very dangerous cracks.

Conventional plaque assays rely on the use of overlays to restrict viral infection allowing the formation of distinct foci that grow in time as the replication cycle continues leading to counta-ble plaques that are visualized with standard techniques such as crystal violet, neutral red or immunolabeling. This classical approach takes several days until large enough plaques can be visualized and counted with some variation due to subjectivity in plaque recognition. Since plaques are clonal lesions produced by virus-induced cytopathic effect, we applied DNA fluores-cent dyes with differential cell permeability to visualize them by live cell imaging. We could observe different stages of that cytopathic effect corresponding to an early wave of cells with chromatin-condensation followed by a wave of dead cells with membrane permeabilization within plaques generated by different animal viruses. This approach enables an automated plaque identification using image analysis to increase single plaque resolution compared to crystal violet counterstaining and allows its application to plaque tracking and plaque reduction assays to test compounds for both antiviral and cytotoxic activities. This fluorescent real-time plaque assay sums to those next-generation technologies by combining this robust classical method with modern fluorescence microscopy and image analysis approaches for future applica-tions in virology.

Seismic imaging is the main technology used for subsurface hydrocarbon prospection. It~provides an image of the subsurface using the same principles as ultrasound medical imaging. As for any data acquired through hydrophones (pressure sensors) and/or geophones (velocity/acceleration sensors), the raw seismic data are heavily contaminated with noise and unwanted reflections that need to be removed before further processing. Therefore, the noise attenuation is done at an early stage and often while acquiring the data. Quality control (QC) is mandatory to give confidence in the denoising process and to ensure that a costly data re-acquisition is not needed. QC is done manually by humans and comprises a major portion of the cost of a typical seismic processing project. It is therefore advantageous to automate this process to improve cost and efficiency. Here, we propose a supervised learning approach to build an automatic QC system. The~QC system is an attribute-based classifier that is trained to classify three types of filtering (mild = under filtering, noise remaining in the data; optimal = good filtering; harsh = over filtering, the signal is distorted). The attributes are computed from the data and represent geophysical and statistical measures of the quality of the filtering. The system is tested on a full-scale survey (9000 km²) to QC the results of the swell noise attenuation process in marine seismic data.

Dynamic contrast-enhanced MRI (DCE-MRI) is increasingly used to quantify and map the spatial distribution of blood-brain barrier (BBB) leakage in neurodegenerative disease, including cerebral small vessel disease and dementia. However, the subtle nature of leakage and resulting small signal changes make quantification challenging. While simplified one-dimensional simulations have probed the impact of noise, scanner drift, and model assumptions, the impact of spatio-temporal effects such as gross motion, k-space sampling and motion artefacts on parametric leakage maps has been overlooked. Moreover, evidence on which to base the design of imaging protocols is lacking due to practical difficulties and the lack of a reference method. To address these problems, we present an open-source computational model of the DCE-MRI acquisition process for generating four-dimensional Digital Reference Objects (DROs), using a high-resolution brain atlas and incorporating realistic patient motion, extra-cerebral signals, noise and k-space sampling. Simulations using the DROs demonstrated a dominant influence of spatio-temporal effects on both the visual appearance of parameter maps and on measured tissue leakage rates. The computational model permits a greater understanding of the sensitivity and limitations of subtle BBB leakage measurement and provides a non-invasive means of testing and optimising imaging protocols for future studies.

Electron Beam Melting (EBM) is an increasingly used Additive Manufacturing (AM) technique employed by many industrial sectors, including the medical device and aerospace industries. In-process EBM monitoring for quality assurance purposes has been a popular research area. Electronic imaging has recently been investigated as one of the in-process EBM data collection methods, alongside thermal/ optical imaging techniques. Despite certain capabilities of an electronic imaging system have been investigated, experiments are yet to be carried out to benchmark one of the most important features of any imaging systems – spatial resolution. This article addresses this knowledge gap by: (1) proposing an indicator for the estimation of spatial resolution which includes the Backscattered Electrons (BSE) information depth, (2) estimating the achievable spatial resolution when electronic imaging is carried out inside an Arcam A1 EBM machine, and (3) presenting an experimental method to conduct edge resolution evaluation with the EBM machine. Analyses of experimental results indicated that the spatial resolution was of the order of 0.3mm-0.4mm when electronic imaging was carried out at room temperature. It is believed that by disseminating an analysis and experimental method to estimate and quantify spatial resolution, this study has contributed to the on-going quality assessment research in the field of in-process monitoring of the EBM process.

Background: The management of erectile dysfunction (ED) shows several grey zones and new treatments for reduce the percentage of patients who discontinued the treatment are required. Here, we aim to evaluate the role of a natural mixture of named Icarifil (L-Citrulline, L-Carnitine, Eruca vesicaria, Panax ginseng, Tribulus terrestris, Turnera diffusa, Taurine, Vitamin E, Zinc) in the management of patients with ED. Methods: From September 2022 to March 2023, all patients attending 3 urological institutions due to ED were randomized to receive: Icarifil 1 sachet every 24 h (Group 1) or Icarifil 1 sachet + tadalafil 5 mg 1 tablet every 24 h (Group 2) or tadalafil 5 mg 1 tablet daily (Group 3), for 3 months. All patients underwent urologic visit and dedicated questionnaires (IIEF-5, SEP-2, SEP-3) at the enrollment and at the follow-up evaluation (3 months). Patient Reported Outcomes (PROs) at the follow-up evaluation were used. Primary endpoint was the difference in the questionnaires at the follow-up visit when compared with enrollment among the study groups. Results: In the per-protocol analysis, 52 patients in the Group 1, 55 in the Group 2 and 57 in Group 3 have been analyzed. At the follow-up evaluation, IIEF-5 have been improved in all the 3 Groups between enrollment and follow-up evaluation, but a statistically significant difference has been reported between Group 2 (+7.4) versus Group 1 (+4.1) or 3 (+5.1), (p&lt;0.001; p&lt;0.001). Moreover, 47 patients (94.0%) in the Group 2 showed an improvement in the SEP questionnaires, when compared with the baseline, while 29 in the Group 1 (56.9%) and 42 in the Group 3 (82.3%) with a statistically significant difference (p=0.004; p=0.003) among the Groups. The PROs analysis reported a better efficacy and patients’ satisfaction in Group 2 when compared with Group 1 or 3. Conclusions: In conclusion, Icarifil is able to improve penile erectile function in mild–moderate ED and it is able to significantly improve the clinical efficacy of tadalafil 5 mg daily use. Icarifil could be represent an interesting alternative treatment in patients experiencing adverse effects or with contraindications for chronic treatment with PDE5-is.

Diabetes mellitus (DM) is one of the major risk factors for COVID-19 complications as it is one of the chronic immune-compromising conditions especially if patients have uncontrolled diabetes, poor HbA1c &/or irregular blood glucose levels. Diabetic patient’s mortality rates with COVID-19 are higher than cardiovascular or cancer patients. Recently Bacillus Calmette–Guérin (BCG) has shown successful results in reversing diabetes in both rats and clinical trials based on different mechanisms from aerobic glycolysis to Beta cells regeneration. BCG is a multi-face vaccine that has been used extensively in protection from TB and leprosy and has been repositioned for treatment of bladder cancer, diabetes & multiple sclerosis. Recently, the COVID-19 epidemiological study confirmed that universal BCG vaccination reduced morbidity and mortality in certain geographical areas. Countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies that have shown low numbers of reported COVID-19 cases. Some countries have started clinical trials that included a single dose BCG vaccine as prophylaxis from COVID-19 or an attempt to minimize its side effects. This proposed research aims to use BCG vaccine as a double-edged weapon countering both COVID-19 & diabetes, not only as protection but also as therapeutic vaccination. The work includes a case study of regenerated pancreatic beta cells based on improved C-peptide & PCPRI laboratory findings after BCG vaccination for a 9 years’ patient. The patient was re-vaccinated based on a negative tuberculin test & no scar at the site of injection of the 1st BCG vaccination at birth. Furthermore, the authors in the present article described a prospective BCG multi-dose clinical study in full details that they will apply in case of acceptance of their submitted grant & the ethical committee approval. The aim of the clinical study is to check if double dose BCG (4 weeks apart) will show a significant difference in the protection of health care professionals in Egypt. The authors suggest and invite the scientific community to take into consideration the concept of direct BCG re-vaccination (after 4 weeks) because of the reported gene expressions & exaggerated innate immunity consequently. As the diabetic MODY-5 patient (mutation of HNF1B, Val2Leu) was on low dose Riomet® while eliminating insulin gradually, a simple analytical method for metformin assay was recommended to ensure its concentration before use as it is not approved yet by the Egyptian QC labs.

Abstract: We review the development and application of an organic polymer-gel capable of producing fixed, three-dimensional fluorescent images of complex radiation fields. The gel consists for more than 99% of γ-ray-polymerized (~15% conversion) tertiary-butyl acrylate (TBA) containing ~100 ppm of a fluorogenic compound, e.g. maleimido-pyrene (MPy). The radio-fluorogenic effect depends on copolymerization of the MPy into growing chains of TBA on radiation-induced polymerization. This converts the maleimido residue, which quenches the pyrene fluorescence, into a succinimido moeity (SPy), which doesn't. The intensity of the fluorescence is proportional to the yield of free-radicals formed and hence to the local dose deposited. Because the SPy moieties are built into the cross-linked polymer matrix the image is fixed. The method of preparing the gel and imaging the radiation-induced fluorescence are presented and discussed. The effect is illustrated with fluorescent images of the energy deposited in the gel by beams of X-rays, electrons and protons as well as a radioactive isotope.

Psoriasis is a chronic immune-mediated skin disease that involves interaction of both immune and skin cells, and is characterized by cytokine-driven epidermal hyperplasia, deviant differentiation, inflammation and angiogenesis. Because available treatments for psoriasis have significant limitations, dietary products are potential natural sources of therapeutic molecules, which can rescind molecular defects associated with psoriasis and could be developed for its management. Fisetin (3,7,3′,4′- tetrahydroxyflavone), a phytochemical naturally found in pigmented fruits and vegetables has demonstrated pro-apoptotic and antioxidant effects in several malignancies. This study utilized biochemical, cellular, pharmacological and tissue-engineering tools to characterize the effects of fisetin on normal human epidermal keratinocytes (NHEKs), peripheral blood mononuclear cells (PBMC) and CD4+ T lymphocytes in 2D and 3D psoriasis-like disease models. Fisetin treatment of NHEKs dose and time-dependently induced differentiation and inhibited interleukin-22-induced proliferation, as well as activation of the PI3K/Akt/mTOR pathway. Fisetin treatment of TNF-α-stimulated NHEKs significantly inhibited the activation of p38 and JNK, but had no effect on ERK1/2. In addition, fisetin treatment significantly decreased the secretion of Th1/Th-17 pro-inflammatory cytokines, particularly IFNγ and IL-17A by 12-O- tetradecanolylphorbol 13-acetate (TPA)-stimulated NHEKs and anti-CD3/CD28-activated human PBMCs. Furthermore, we established the in-vivo relevance of fisetin functions, using a 3D full-thickness human skin model of psoriasis (FTRHSP) that closely mimics in-vivo human psoriatic skin-lesions. Herein, fisetin significantly ameliorated psoriasis-like disease features, and decreased the production of IL-17 by CD4+ T lymphocytes co-cultured with FTRHSP. Collectively, our data identify pro-differentiative, anti-proliferative and anti-inflammatory effects of fisetin, via modulation of PI3K-Akt-mTOR and p38/JNK pathways and the production of cytokines in 2D and 3D human skin model of psoriasis. These results suggest that fisetin has a great potential to be developed as an effective and inexpensive agent for the treatment of psoriasis and other related inflammatory skin disorders.

This study unveils verapamil's compelling cytoprotective and proliferative effects on pancreatic β-cells amidst diabetic stressors, spotlighting its unforeseen role in augmenting cholecystokinin (CCK) expression. Through rigorous investigations employing MIN6 β-cells and zebrafish models under type 1 and type 2 diabetic conditions, we demonstrate verapamil's capacity to significantly boost β-cell proliferation, enhance glucose-stimulated insulin secretion, and fortify cellular resil-ience. A pivotal revelation of our research is verapamil's induction of CCK, a peptide hormone known for its role in nutrient digestion and insulin secretion, which signifies a novel pathway through which verapamil exerts its therapeutic effects. Furthermore, our mechanistic insights reveal that verapamil orchestrates a broad spectrum of gene and protein expressions pivotal for β-cell survival and adaptation to immune-metabolic challenges. In vivo validation in a zebrafish larvae model confirms verapamil's efficacy in fostering β-cell recovery post-metronidazole inflic-tion. Collectively, our findings advocate for verapamil's reevaluation as a multifaceted agent in diabetes therapy, highlighting its novel function in CCK upregulation alongside enhancing β-cell proliferation, glucose sensing, and oxidative respiration. This research enriches the therapeutic landscape, proposing verapamil not only as a cytoprotector but also as a promoter of β-cell re-generation, thereby offering fresh avenues for diabetes management strategies aimed at pre-serving and augmenting β-cell functionality.

Ewing sarcoma (ES) is an aggressive bone and soft-tissue pediatric cancer. High vitronectin (VN) expression has been associated with poor prognosis in other cancers, and we aimed to determine the utility of this extracellular matrix glycoprotein as a biomarker of aggressiveness in ES. Silk-fibroin plus gelatin-tyramine hydrogels (HGs) were fabricated with and without cross-linked VN and cultivated with A673 and PDX73 ES cell lines for two and three weeks. VN secretion to culture media was assessed using ELISA. Morphometric analysis was applied for phenotypic characterization. VN release to culture media was higher in 3D-models than in monolayer cultures, and intracellular, intercellular and pericluster presence was also observed. A673-HGs showed lower density of clusters but a proportion of larger clusters than PDX73-HGs, which presented low cluster circularity. The cluster density of A673-HGs without added VN was higher than with added VN, and slightly lower in the case of PDX73-HGs. Furthermore, a culture time of three weeks provided no benefits in cluster growth compared to two weeks, especially in A673 -HGs. These advances in 3D modeling and digital quantification pave the way for future studies in ES and other cancers to deepen understanding about intra- and intercellular heterogeneity and anti-adhesion VN therapies.

Immediate load of full-arch rehabilitations over implants, specially over 4 implants are very well documented in the literature. More recently, the use of computed surgical guides to help the planning and the execution of these treatments, in many situations without the need of raising a flap, and diminishing the appearance of hematomas, bleeding and with less trauma to the patient has gained preference among implantologists. The objective of this case report is to show a clinical case of an immediate load full-arch fixed rehabilitation over 4 implants produced by 3D printing manufacturing technology, and placed with a computed surgical guide, in the same appointment, and the 24 months follow-up. The patient returned after 3 months to replace the immediate temporary fixed prosthesis for a new one, with metallic bar, better teeth and more delicate. Soft and hard tissue around the implants seemed to be stable, without signs of inflammation, either on the 3 or the 24 months follow-up. 3D printing of implants by direct metal laser sintering is a technology that seems to be promising for oral implantology, with solid studies showing reliable results, as seen in this single case. More clinical studies are necessary to testify its efficacy.

Compound-specific isotope analysis (CSIA) can provide unique insights into the cycling of elements including carbon and nitrogen. One approach for CSIA is the use of high-performance liquid chromatography (HPLC) to separate compounds of interest, followed by analysis of these compounds using an elemental analyzer coupled to an isotope ratio mass spectrometer. A key component of this technique is the fraction collector, which automatically collects compounds as they are separated by HPLC. Here we present a fraction collector which is a simple adaptation of a 3D printer, and thus can be easily adopted by any laboratory already equipped for HPLC. In addition to the much lower cost compared to commercial alternatives, this adaptation has the advantage for CSIA that the 3D-printer is able to heat the collected fractions, which is not true for many commercial fraction collectors. Heating allows faster evaporation of the solvent, so that the dried compounds can be measured by EA-IRMS immediately. The procedure can be repeated consecutively so that dilute solutions can have the compounds concentrated for analysis. Any computer-controlled HPLC can be integrated to the fraction collector used here by means of AutoIt.

Recanalization poses challenge in coil embolization for cerebral aneurysms. Establishing predictive models for post-embolization recanalization is important for clinical decision-making. However, conventional statistical and machine learning (ML) models may overlook critical parameters during the initial selection process. In this study, we automated the identification of significant hemodynamic parameters using a PointNet-based deep neural network (DNN), leveraging their inherent 3D features. Further feature analysis was conducted utilizing saliency mapping, an explainable artificial intelligence (XAI) technique. The study encompassed the analysis of velocity, pressure, and wall shear stress (WSS) in both pre- and post-coiling models derived from computational fluid dynamic (CFD) simulations for 59 aneurysms. Velocity was identified as the most pivotal parameter, supported by the lowest P-value from statistical analysis and the highest area under the curves (AUROC)/precision-recall curves (AUPRC) values from DNN model. Moreover, visual XAI analysis revealed robust injection flow zones with notable impingement points in pre-coiling models, as well as pronounced interplay between flow dynamics and the coiling plane were important 3D features in identifying the recanalized aneurysms. The combination of DNN and XAI was found to be an accurate and explainable approach not only at predicting post-embolization recanalization but also at discovering unknown features in the future.

Background. Currently, most of the research in breast cancer has been carried out in conventional two-dimensional (2D) cell culture due to its practical benefits, however, the three-dimensional (3D) cell culture is becoming the model of choice in cancer research because it allows cell-cell and cell-extracellular matrix (ECM) interactions, mimicking the native microenvironment of tumors in vivo. Methods. in this work, we evaluated the effect of 3D cell organization on the expression pattern of miRNAs (by Small-RNAseq) and mRNAs (by microarrays) in the breast cancer SKBR3 cell line and analyzed the biological processes and signaling pathways regulated by the differ-entially expressed protein-coding genes (DE-mRNAs) and miRNAs (DE-microRNAs) found in the organoids. Results. We obtained well-defined cell-aggregated organoids with a grape cluster-like morphology with a size up to 9.2×105 μm3. The transcriptomic assays showed that cell growth in organoids significantly affected (all p < 0.01) the gene expression patterns of both, miRNAs and mRNAs, finding 20 upregulated and 19 downregulated DE-microRNAs, as well as 49 upregulated and 123 downregulated DE-mRNAs. In silico analysis showed that a subset of 11 upregulated DE-microRNAs target 70 downregulated DE-mRNAs. These genes are involved in 150 gene on-tology (GO) biological processes such as regulation of cell morphogenesis, regulation of cell shape, regulation of canonical Wnt signaling pathway, morphogenesis of epithelium, regulation of cy-toskeleton organization, as well as in the MAPK and AGE-RAGE signaling KEGG-pathways. In-terestingly, hsa-mir-122-5p (Fold Change (FC)=15.4), hsa-mir-369-3p (FC=11.4), and hsa-mir-10b-5p (FC=20.1) regulated up to the 81 % of the 70 downregulated DE-mRNAs. Conclu-sion, the organotypic 3D cell-organization architecture of breast cancer SKBR3 cells impacts the expression pattern of miRNAs-mRNAs network mainly through overexpression of hsa-mir-122-5p, hsa-mir-369-3p, and hsa-mir-10b-5p. All these findings suggest that the interaction between cell-cell and cell-ECM as well as the change in the culture architecture impacts gene ex-pression, and therefore, support the pertinence of migrating breast cancer research from conven-tional cultures to 3D models.

Microwave absorbers with lightweight, good stability and high efficiency have attracted much attention for their applications in many contemporary fields. In this work, the 3D porous (Ni@NO-C)n/NO-C composite absorber was prepared by a wet chemistry method with Ni chains and melamine as precursors, in which NO-C (N,O-doped carbon) encapsulated Ni particles are homogenously dispersed in the 3D porous networks of NO-C in the form of (Ni@NO-C)n chains. The special microstructure of the as-prepared material is proved to be benefit for the improvement of its microwave adsorption performance. The as-synthesized (Ni@NO-C)n/NO-C composite ab-sorber exhibited an effective absorption bandwidth of 4.1 GHz and an extremely large reflection loss of -72.3 dB. The excellent microwave absorbing performances can be ascribed to the coopera-tive consequence of dielectric loss and magnetic loss along with the balance between attenuation capability and impedance match.

This research focused on the perception of visually impaired individuals regarding tactile image creation using 3D printing. We developed and applied an experiment with 28 participants with visual impairments. They performed tasks based on skills whose foundations are needed and used in their daily lives, such as scanning, tactile discrimination, picture and spatial comprehension. The tactile images used in this study were developed by additive manufacturing and printed over 180 g/m² sulphite paper. The best performances were obtained when (1) the tactile image contour line heights were between 0.2 mm and 0.4 mm; and (2) the texture presented densities between 10% and 50%, when alone, or between 10% and 90%, when combined with another texture. The tested line widths (0.8 mm and 1.2 mm) did not present statistically significant differences in the results. Vision status (low vision or blindness) and moment of vision loss (congenital or late blind) did not influence the results. Schooling affected the activities of identifying objects and locating their copies. In the Conclusion section, there is a detailed recommendation list for the production and application of tactile materials, which range from simplifying forms to encouraging the use of both hands during content assimilation.

In this work, we introduce a scalable and efficient GPU-accelerated methodology for volumetric particle advection and finite-time Lyapunov exponent (FTLE) calculation, focusing on the analysis of Lagrangian Coherent Structures (LCS) in large-scale Direct Numerical Simulation (DNS) datasets across incompressible, supersonic, and hypersonic flow regimes. LCS play a significant role in turbulent boundary layer analysis, and our proposed methodology offers valuable insights into their behavior in various flow conditions. Our novel owning-cell locator method enables efficient, constant-time cell search, and the algorithm draws inspiration from classical search algorithms and modern multi-level approaches in numerical linear algebra. The proposed method is implemented for both multi-core CPUs and Nvidia GPUs, demonstrating strong scaling up to 32,768 CPU cores and up to 62 Nvidia V100 GPUs. By decoupling particle advection from other problems, we achieve modularity and extensibility, resulting in consistent parallel efficiency across different architectures. Our methodology was applied to calculate and visualize the FTLE on four turbulent boundary layers at different Reynolds and Mach numbers, revealing that coherent structures grow more isotropic proportional to the Mach number, and their inclination angle varies along the streamwise direction. We also observed increased anisotropy and FTLE organization at lower Reynolds numbers, with structures retaining coherency along both spanwise and streamwise directions. Additionally, we demonstrated the impact of lower temporal frequency sampling by upscaling with an efficient linear upsampler, preserving general trends with only 10% of the required storage. In summary, we present a particle search scheme for particle advection workloads in the context of visualizing LCS via FTLE that exhibits strong scaling performance and efficiency at scale. Our proposed algorithm is applicable across various domains requiring efficient search algorithms in large structured domains. While this manuscript focuses on the methodology and its application to LCS, an in-depth study of the physics and compressibility effects in LCS candidates will be explored in a future publication.

Auto-labeling is one of the main challenges in 3D vehicle detection. Auto-labeled datasets can be used to identify objects in LiDAR data, which is a challenging task due to the large size of the dataset. In this work, we propose a novel methodology to generate new 3D based auto-labeling datasets with a different point of view setup than the one used in the most recognized datasets (KITTI, WAYMO, etc.). The performance of the methodology has been further demonstrated with the development of our own dataset with the auto-generated labels and tested under boundary conditions on a bridge in a fixed position. The proposed methodology is based on the YOLO model trained with the KITTI dataset. From a camera-LiDAR sensory fusion, it is intended to auto-label new datasets while maintaining the consistency of the Ground Truth. The main contribution of this work is a novel methodology to auto-label autonomous driving datasets using YOLO as the main labelling system. The performance of this approach is measured retraining the contrast models of the KITTI benchmark.

Evidence regarding the effect of the onlay preparation design for different CAD/CAM restorative materials considering the preservation of cusps is lacking. Molars were 3D modeled in four preparation designs for onlay restoration: traditional design with functional cusp coverage (TFC), non-retentive design with functional cusp coverage (NFC), traditional design with non-functional cusp coverage (TNFC), non-retentive design with non-functional cusp coverage (NNFC). Restorations were simulated with two CAD/CAM restorative materials: LD – lithium disilicate (IPS e.max CAD) and RC - resin composite (GrandioBloc). A 100 N axial load was applied to the occlusal surface simulating the centric contact point. Von Mises (VM) and maximum principal (Pmax) stresses were evaluated for restorations, cement layer and dental substrate. The non-retentive preparation design reduced the stress concentration in the tooth structure in comparison to the conventional retentive design. For LD onlays, the stress distribution on the restoration intaglio surface showed that the preparation design as well as the prepared cusp, influenced the stress magnitude. The non-retentive preparation design provided better load distribution in both restorative materials and more advantageous for tooth structure. The resin composite restoration on non-functional cusp is recommended when functional cusp is preserved, in order to associate conservative dentistry and low stress magnitude.

Shales are well known for their strong anisotrophic properties. The classical Athy’s model on the exponential porosity reduction with the depth commonly uses based on localities only. Shale compaction curve affects the results of the basin modeling as it is important input data, thus the standard compaction curve of shales needs to be established. This study provided a new data and complies available data of Thailand shales to propose the new empirical relationship among porosity, burial depth, and geological age. The numerical data of the geological time were estimated by the application from the relationship of velocity and depth in each geological ages. The variation of the Thailand shale data due to the different geological ages was found in this study. Finally, the standard curve of shale compaction proposed by Puttiwongrak et al. [9] was examined and confirmed by this research findings.