As part of our research for new leads against human African trypanosomiasis (HAT), we report on a 3D-QSAR study for antitrypanosomal activity and cytotoxicity of aminosteroid-type alkaloids recently isolated from the African medicinal plant Holarrhena africana A. DC. (Apocynaceae), some of which are strong trypanocides against Trypanosoma brucei rhodesiense (Tbr) with low toxicity against mammalian cells. Fully optimized 3D molecular models of seventeen congeneric Holarrhena alkaloids were subjected to a comparative molecular field analysis (CoMFA). CoMFA models were obtained for both, the anti-Tbr and cytotoxic activity data. Model performance was assessed in terms of statistical characteristics (R², Q² and P² for partial least squares (PLS) regression, internal cross-validation (leave-one-out) and external predictions (test set), respectively, as well as the corresponding SDEP and F-values). With R²=0.99, Q²=0.83 and P²=0.79 for anti-Tbr activity and R²=0.94, Q²=0.64, P²=0.59 for cytotoxicity against L6 rat skeletal myoblasts, both models were of good internal and external predictive power. The regression coefficients of the models representing the most prominent steric and electrostatic effects on anti-Tbr and for L6 cytotoxic activity were translated into contour maps and analyzed visually, allowing suggestions for possible modification of the aminosteroids to further increase the antitrypanosomal potency and selectivity. Very interestingly, the 3D-QSAR model established with the Holarrhena alkaloids also applied to the antitrypanosomal activity of two aminocycloartane-type compounds recently isolated by our group from Buxus sempervirens L. (Buxaceae), which indicates that these structurally similar natural products share a common SAR and, possibly, mechanism of action with the Holarrhena steroids. This 3D-QSAR study has thus resulted in plausible structural explanations of the antitrypanosomal activity and selectivity of aminosteroid- and aminocycloartane-type alkaloids as an interesting new class of trypanocides and may represent a starting point for lead optimization.

Fatty Acid Amide Hydrolase (FAAH) is one of the enzymes responsible of endocannabinoids metabolism. The inhibition of FAAH is a useful and indirect strategy to raise endogenous cannabinoid concentrations, which would be useful for the treatment of various pathological processes in which cannabinoid concentrations are lowered. In the present work, we present an extensive 3D-QSAR/CoMSIA study on a series of 90 irreversible inhibitors of FAAH of pyrimidinyl-piperazine-carboxamide structure. The final model obtained was extensively validated (q2 = 0.734; r2test = 0.966; r2m = 0.723), and based on the information derived from the contour maps we reported a series of 10 new compounds designed as powerful FAAH inhibitors (pIC50 of the best-proposed compounds = 12.196; 12.416).

(1) Background: Type-2 Diabetes (T2DM) is a long-term medical disorder characterized by Insulin deficiency and high blood glucose levels. Among other medication to cure T2DM, the review of the literature found that various Pyrimidine derivative act as an agonist for G-protein-coupled receptor 119 (GPR119) was proposed to control blood glucose levels by enhancing the function of pancreatic beta-cells and its mechanism of action with fewer adverse effects.; (2) Methods: In the present research work, in-silico investigations were carried out to investigate the potential of Pyrimidine analogue as an agonists to the protein target GPR119 receptor. We performed exhaustive molecular modelling and protein modelling methodologies such as homology mod-elling, molecular docking along with various drug designing tools such as 3D-QSAR and pharmacophore mapping to ascertain the design of better GPR119 agonists.; (3) Results: On the basis of in-depth computa-tional studies, we designed new pyrimidine moiety and analyzed them for GPR-119 receptor agonist and fur-ther explored the ADME properties. Designed compounds found to exhibit better predicted activities as com-pared to reference compound; (4) Conclusions: The current research on pyrimidine derivatives, using molec-ular docking, 3D-QSAR and Pharmacophore mapping demonstrated that the obtained computational model has significant properties and the designed molecules and Dataset from this model, produced antidiabetic compound against the target GPR119 i.e., compound 1S, 1Z and 1D with the docking score of −11.696, -9.314 and -8.721 respectively. The pharmacokinetics and drug-likeness studies revealed that these compounds may be the future candidate for the treatment of diabetes acting via GPR119 agonist mechanism.

The dopamine D3 receptor is an important CNS target for the treatment of a variety of neurological diseases. Selective dopamine D3 receptor antagonists modulate the improvement of psychostimulant addiction and relapse. In this study, five and six featured pharmacophore models of D3R antagonists were generated and evaluated with the post-hoc score combining two survival scores of active and inactive. Among Top 10 models, APRRR215 and AHPRRR104 were chosen based on the coefficient of determination (APRRR215: R2training = 0.80; AHPRRR104: R2training = 0.82) and predictability (APRRR215: Q2test = 0.73, R2predictive = 0.82; AHPRRR104: Q2test = 0.86, R2predictive = 0.74) of their 3D-quantitative structure–activity relationship models. Pharmacophore-based virtual screening of a large compound library from eMolecules (> 3 million compounds) using two optimal models expedited the search process 100-fold speed increase compared to the docking-based screening (HTVS scoring function in Glide) and identified a series of hit compounds having promising novel scaffolds. After the screening, docking scores, as an adjuvant predictor, were added to two fitness scores (from the pharmacophore models) and predicted Ki (from PLSs of the QSAR models) to improve accuracy. Final selection of the most promising hit compounds were also evaluated for CNS-like properties as well as expected D3R antagonism.

Precise binding affinity predictions are essential for structure-based drug discovery (SBDD). Focal adhesion kinase (FAK) is a member of the tyrosine kinase protein family and is overexpressed in a variety of human malignancies. Inhibition of FAK using small molecules is a promising therapeutic option for several types of cancer. Here, we conducted computational modeling of FAK targeting inhibitors using 3-dimensional structure-activity relationship (3D-QSAR), molecular dynamics (MD), and hybrid topology-based free energy perturbation (FEP) methods. The structure-activity relationship (SAR) studies between the physicochemical descriptors and inhibitory activities of the chemical compounds were performed with reasonable statistical accuracy using CoMFA and CoMSIA. These are two well-known 3D-QSAR methods based on the principle of supervised machine learning (ML). Essential information regarding residue-specific binding interactions was determined using the MD and MM-PB/GBSA methods. Finally, physics-based relative binding free energy (〖∆∆G〗_RBFE^(A→B)) values of analogous ligands were estimated using the alchemical FEP simulation. An acceptable agreement was observed between the experimental and computed relative binding free energies. The overall results using ML and physics-based hybrid approaches could be useful for the rational optimization of accessible lead compounds with similar scaffolds targeting the FAK receptor.

Reducing the levels of toxic chemicals that cause adverse health and environmental impacts is a challenge for the international community. There is a need of a global strategy. Indeed, too often the problems associated to the exposure of chemical substances is recognized a posteriori, in the presence of consequences already observed. The prediction of the likely effects of chemical exposure on human health is based on classical tests with animals, which are time and money consuming, may deviate from an accurate prediction towards humans, and arises ethical concerns. Regulations are now considering the adoption of in silico (or computational) methods, which can be used for prioritizing substances according to the probability to be toxic for the biosphere. Several initiatives have prioritized chemicals, typically based according to some criteria, such as chemicals which may be endocrine disruptors, or persistent, bioaccumulative, or toxic (PBT). However, these initiatives focused on a certain range of adverse properties, and covered a certain number of substances only. We applied a set of largely validated and widely used predictive methods to large collections of chemicals: (i) to about 340,000 with a defined function, and (ii) to about 6 millions, which have been synthetized. The aim of this study is to quantify the putative impact of existing and future chemicals on towards human health, ecological and environment properties. The impact on the environment is the cause of major concern. This is the case of pesticides and hazardous, which is quite expected; however, also pharmacologically active candidate compounds of natural origin may have a high level of ecotoxicity. Pesticides and hazardous are also the categories of higher concern for humans, followed by pharmaceuticals. The pesticides and the hazardous are the categories of higher concern also on the environmental point of view. The results of our analysis could be the basis for the identification of new safety rules.

A common task in the immunodetection of structurally close compounds is to analyze the selectivity of immune recognition: it is required to understand the regularities of immune recognition and to elucidate the basic structural elements which provide it. Triazines are compounds of particular interest for such a research due to their high variability and the necessity of their monitoring to provide safety of agricultural products and foodstuffs. We evaluated the binding of 20 triazines with polyclonal (pAb) and monoclonal (mAb) antibodies obtained using atrazine as the immunogenic hapten. A total of >3000 descriptors was used in QSAR analysis of binding activities (pIC50). Comparison of the two enzyme immunoassay systems showed that the system with pAb is much easier to describe using 2D QSAR methodology, while the system with mAb can be described using the 3D QSAR COMFA. Thus, for the 3D QSAR model of the polyclonal antibodies, the main statistical parameter q² (‘leave-many-out’) is equal 0.498, and for monoclonal antibodies q² is equal 0.566. Obviously, in the case of pAb, we deal with several targets, while in the case of mAb the target is one, and therefore it is easier to describe it using specific fields of molecular interactions distributed in space.

Ability of quantitative structure – property / activity relationships (QSPRs/QSARs) to serve for epistemological processes in natural sciences is discussed. Some weirdness of QSPR/QSAR state-of-art are listed. There are some contradictions in the research results in this area. Sometimes, these should be classified as paradoxes or weirdness. These points often are ignored. Here these are listed and briefly commented. In addition, hypothesises on the future evolution of the QSPR/QSAR theory and practice are suggested.

Histone Lysine Specific Demethylase 1 (LSD1) is overexpressed in many cancers and become a new target for anticancer drugs. In recent years, the small molecule inhibitors with various structures targeting LSD1 have been reported. Here we report the binding interaction modes of a series of thieno[3,2-b]pyrrole-5-carboxamides LSD1 inhibitors using molecular docking, three dimensional quantitative structure-activity relationship (3D-QSAR). Comparative molecular field analysis (CoMFA q²=0.783, r²=0.944, r²_pred=0.851) and Comparative molecular similarity indices analysis (CoMSIA q²=0.728, r²=0.982, r²_pred=0.814) were used to establish 3D-QSAR models, which had good verification and prediction capabilities. Based on the contour maps and the information of molecular docking, 8 novel small molecules were designed in silico, among which compounds D4, D5 and D8 with high predictive activity were subjected to further molecular dynamics simulations (MD), and their possible binding modes were explored. It was found that Asn535 plays a crucial role in stabilizing the inhibitors. Furthermore, the ADME and bioavailability prediction for D4, D5 and D8 were carried out. The results would provide valuable guidance for designing new reversible LSD1 inhibitors in the future.

Some novel (phenyl-diazenyl)phenols (3a–g) were designed and synthesized to be evaluated for their antimicrobial activity. A previously synthesized molecule, active against bacteria and fungi, was used as lead for modifications and optimization of the structure, by introduction/removal or displacement of hydroxyl groups on the azobenzene rings. The aim of this work was to evaluate the consequent changes of the antimicrobial activity and to validate the hypothesis that, for these compounds, a plausible mechanism could involve an interaction with protein receptors, rather than an interaction with membrane. All newly synthesized compounds were analyzed by ¹H nuclear magnetic resonance (NMR), DSC thermal analysis and UV-Vis spectroscopy. The in vitro minimal inhibitory concentrations (MIC) of each compound was determined against Gram-positive and Gram-negative bacteria and Candida albicans. Compounds 3b and 3g showed the highest activity against S. aureus and C. albicans, with remarkable MIC values of 10 µg/mL and 3 µg/mL, respectively. Structure- activity relationship studies were capable to rationalize the effect of different substitutions on the phenyl ring of the azobenzene on antimicrobial activity.

2-(Morpholin-4-yl)-4,5-bis(2’’,2’’,2’’-trinitroethoxy)-1,3,5-triazine having QSAR-predicted anti-tumor activity was tested for the cytotoxicity using MTT and LDH cell viability tests. The experiments were conducted using human fibroblasts, peripheral blood mononuclear cells and breast cancer cells and allowed to identify effective cytotoxic concentration ant therapeutic range of this compound. The data obtained suggest the feasibility of the further studies of the test compound as a potential anti-cancer agent.

Terpenoids, including monoterpenoids (C₁₀), norisoprenoids (C₁₃) and sesquiterpenoids (C₁₅), constitute a large group of plant-derived naturally occurring secondary metabolites which chemical structure is highly diverse. A quantitative structure-activity relationship (QSAR) model to predict the terpenoids toxicity and to evaluate the influences of their chemical structure, was developed in this study, by assessing the toxicity of 27 terpenoid standards using Gram-negative bioluminescent Vibrio fischeri, in real time. Under the test conditions, at concentration of 1 µM, the terpenoids showed a toxicity level lower than five %, with exception of geraniol, citral, (S)-citronellal, geranic acid, (±)-α-terpinyl acetate and geranyl acetone. Moreover, the standards tested displayed a toxicity level higher than 30 % at concentration of 50 to 100 µM, with the exception of (+)-valencene, eucalyptol, (+)-borneol, guaiazulene, β-caryophellene and linalool oxide. Regarding the functional group, the terpenoids toxicity was observed in the following order: alcohol > aldehyde ~ ketone > ester > hydrocarbons. CODESSA software was employed to develop the QSAR models based on the correlation of terpenoids toxicity and a pool of descriptors related to each chemical structure. The QSAR models, based on t-test values, showed that terpenoids toxicity was mainly attributed to geometric (e.g., asphericity) and electronic (e.g., max partial charge for a C atom [Zefirov's PC]) descriptors. Statistically, the most significant overall correlation was the four-parameter equation with training and test coefficient correlation higher than 0.810 and 0.535, respectively, and square coefficient of cross-validation (Q²) higher than 0.689. According to the obtained data, the QSAR models are a suitable and a rapid tool to predict the terpenoids toxicity in a diversity of food products.

Biofilms are congregations of bacteria on a surface, and they grow into obstacles for the functionalities of any device or machinery involves anything biological. Biofilms are developed through a biochemical system known as ‘Quorum Sensing’ that accounts for the chemical signaling that direct either biofilm formation or inhibition. Computational models that relate chemical and structural features of compounds to their performance properties have been used to aide in the discovery of active small molecules for many decades. These quantitative structure-activity relationship (QSAR) models are also important for predicting the activity of molecules that can have a range of effectiveness in biological systems. This study uses QSAR methodologies combined with and different machine learning algorithms to predict and assess the performance of several different compounds acting in Quorum Sensing. Through computational probing of the quorum sensing molecular interaction, new design rules can be elucidated for countering biofilms.

Prototype of a family of at least nine members, c-src tyrosine kinase is a therapeutically interesting target, because its inhibition might be of interest not only in a number of malignancies, but also in a diverse array of conditions, from neurodegenerative pathologies to certain viral infections. Computational methods in drug discovery are considerably cheaper than conventional methods and offer opportunities of screening very large numbers of compounds in conditions that would be simply impossible within the wet lab experimental settings. We have explored the use of global QSAR models and molecular ligand docking in the discovery of new c-src tyrosine kinase inhibitors. Using a data set of 1038 compounds from ChEMBL and 19 blocks of molecular descriptors, we have developed over 200 QSAR classification models, based on six machine learning algorithms and 17 feature selection methods. We have selected 49 with reasonably good performance (positive predictive value and balanced accuracy higher than 70% in nested cross validation) and the models were assembled by stacking with a simple majority vote and used for the virtual screening of over the “named” ZINC data set (over 100,000 compounds). 744 compounds were predicted by at least 50% of the QSAR models as active, 147 compounds were within the applicability domain and predicted by at least 75% of the models to be active. The latter 147 compounds were submitted to molecular ligand docking using Vina and Ledock, and a number of 90 were predicted to be active based on the binding energy. External data from CHEMBL and PUBCHEM confirmed that at least 7.83% (in the case of QSAR) or 6.67% (in the case of integrated QSAR and molecular docking) of the compounds are active on the c-src target.

Nipah virus (NiV) is responsible to cause various outbreaks in Asian countries, with latest from Kerala state of India. Till date there is no drug available despite its urgent requirement. In the current study, we have provided a computational one-stop solution for NiV inhibitors. We have developed “anti-Nipah” web resource, which comprised of a data repository, prediction method, and data visualization modules. The database comprised of 313 (181 unique) inhibitors from different strains and outbreaks of NiV extracted from research articles and patents. However, the quantitative structure–activity relationship (QSAR) based predictors were accomplished using classification approach employing 10-fold cross validation through support vector machine with 120 (68p + 52n) inhibitors. The overall predictor showed the accuracy and Matthew’s correlation coefficient of 88.89% and 0.77 on training/testing dataset respectively. The independent validation dataset also performed equally well. The data visualization modules from chemical clustering and principal component analyses displayed the diversity in the NiV inhibitors. Therefore, our web platform would be of immense help to the researchers working in developing effective inhibitors against NiV. The user-friendly webserver is freely available on URL: http://bioinfo.imtech.res.in/manojk/antinipah/

Topological indices have been used to modeling biological and chemical properties of molecules in quantitive structure property relationship studies and quantitive structure activity studies. All the degree based topological indices have been defined via classical degree concept. In this paper we define a novel degree concept for a vertex of a simple connected graph: S degree. And also we define S indices of a simple connected graph by using the S degree concept. We compute the S indices for well-known simple connected graphs such as paths, stars, complete graphs and cycles.

In silico prediction of the in vivo efficacy of siRNA ionizable-lipid nanoparticles is desirable yet never achieved before. This study aims to computationally predict siRNA nanoparticles in vivo efficacy, which saves time and resources. A data set containing 120 entries was prepared by combining molecular descriptors of the ionizable lipids together with two nanoparticles formulation characteristics. Input descriptor combinations were selected by an evolutionary algorithm. Artificial neural networks, support vector machines and partial least squares regression were used for QSAR modeling. Depending on how the data set is split, two training sets and two external validation sets were prepared. Training and validation sets contained 90 and 30 entries respectively. The results showed the successful predictions of validation set log(dose) with R2val = 0.86 – 0.89 and 0.75 – 80 for validation sets one and two respectively. Artificial neural networks resulted in the best R2val for both validation sets. For predictions that have high bias, improvement of R2val from 0.47 to 0.96 was achieved by selecting the training set lipids lying within the applicability domain. In conclusion, in vivo performance of siRNA nanoparticles was successfully predicted by combining cheminformatics with machine learning techniques.

Artificial learning and machine learning is playing a pivotal role is the society especially in the field of medicinal chemistry and drug discovery. Particularly its algorithms, neural networks or other recurrent networks drive this area. In this review, we have taken into account the diverse use of AI in a number of pharmaceutical industries including discovery of drugs, repurposing, development of pharmaceutical drug and its clinical trials. In addition, the efficiency of these artificial or machine learning programs in achieving the target drugs in short time period, along with accurate dosage and cost effectively of the drug has also been discussed. Numerous applications of AI in property prediction such as ADMET have been used for prediction of strength of this technology in QSAR. In case of de-novo synthesis, it results in generation of novel drug molecules with unique design proving this a promising field fir drug design. Moreover, its involvement in synthetic planning, ease of synthesis and much more contribute to automated drug discovery in near future.

Herein, we present a combination of experimental and computational study on the mitochondrial F0F1-ATPase nanotoxicity inhibition induced by single-walled carbon nanotubes (SWCNT-pristine, SWCNT-COOH). To this end, the in vitro inhibition responses in submitochondrial particles (SMP) as F0F1-ATPase enzyme were strongly dependent on the concentration assay (from 3 to 5 µg/ml) for both types of carbon nanotubes. Besides, both SWCNTs show an interaction inhibition pattern like the oligomycin A (the specific mitochondria F0F1-ATPase inhibitor). Furthermore, the best crystallography binding pose obtained for the docking complexes based on the free energy of binding (FEB), fit well with the previous in vitro evidences from the thermodynamics point of view. Following an affinity order as: FEB (oligomycin A/F0-ATPase complex) = -9.8 kcal/mol > FEB (SWCNT-COOH/F0-ATPase complex) = - 6.8 kcal/mol ~ FEB (SWCNT-pristine complex) = -5.9 kcal/mol. With predominance of van der Waals hydrophobic nanointeractions with key F0-ATPase binding site residues (Phe 55 and Phe 64). By the other hand, results on elastic network models, and fractal-surface analysis suggest that SWCNTs induce significant perturbations by triggering abnormal allosteric responses and signals propagation in the inter-residue network which could affect the substrate recognition ligand geometrical specificity of the F0F1-ATPase enzyme in order (SWCNT-pristine > SWCNT-COOH). Besides, the performed Nano-QSTR models for both SWCNTs show that this method may be used for the prediction of the nanotoxicity induced by SWCNT. Overall, the obtained results may open new avenues toward to the better understanding and prediction of new nanotoxicity mechanisms, rational drug-design based nanotechnology, and potential biomedical application in precision nanomedicine.

Read-Across Structure-Activity Relationship (RASAR) is an emerging cheminformatic approach that combines the usefulness of a QSAR model and similarity-based Read-Across predictions. In this work, we have generated a simple, interpretable, and transferable quantitative-RASAR (q-RASAR) model which can efficiently predict the cytotoxicity of TiO2-based multi-component nanomaterials. The data set involves 29 TiO2-based nanomaterials which contain specific amounts of noble metal precursors in the form of Ag, Au, Pd, and Pt. The data set was rationally divided into training and test sets and the Read-Across-based predictions for the test set were generated using the tool Read-Across-v4.1 available from https://sites.google.com/jadavpuruniversity.in/dtc-lab-software/home. The hyperparameters were optimized based on the training set data and using this optimized setting, the Read-Across-based predictions for the test set were obtained. The optimized hyperparameters and the similarity approach, which yields the best predictions, were used to calculate the similarity and error-based RASAR descriptors using the tool RASAR-Desc-Calc-v2.0 available from https://sites.google.com/jadavpuruniversity.in/dtc-lab-software/home. These RASAR descriptors were then clubbed with the physicochemical descriptors and were subjected to features selection using the tool Best Subset Selection v2.1 available from https://dtclab.webs.com/software-tools. The final set of selected descriptors was used to develop multiple linear regression based q-RASAR models, which were validated using stringent criteria as per the OECD guidelines. Finally, a random forest model was also developed with the selected descriptors. The final machine learning model can efficiently predict the cytotoxicity of TiO2-based multi-component nanomaterials superseding previously reported models in the prediction quality.

The main inhibitory neurotransmitter in the mammalian brain is 4-aminobutyric acid (GABA). Phthalimide acts as a sodium channel antagonist, one of the finest targets for treating epilepsy is the sodium channel and JNK kinase activity is inhibited to treat epilepsy. a novel compound with multiple targets of action for the treatment of epilepsy also anti-oxidant activity has been designed. The compounds are designed in two series aldehydes and aniline. Docking of all the designed compounds has been done with the suitable protein GABA-AT, sodium channel, JNK protein, and anti-oxidant from protein bank. QSAR was done for constructing many linear regression models. In combination with the developed Docking and QSAR outcomes, ADMET has been performed for the active compounds. The result shows that 11 of the compounds have excellent binding energy in docking with all the receptors and also have good QSAR results and follow the ADMET. The structural understanding of human GABA-AT inhibition was obtained from molecular dynamics simulation studies for compound no. 11 at 5 nanoseconds. Synthesis and pharmacological activity also suggest that the designed compound no.11 be considered the best Novel Compound.

Histone deacetylases (HDAC) represent promising epigenetic targets for several diseases including different cancer types. The HDAC inhibitors approved to date are pan-HDAC inhibitors and most show a poor selectivity profile, side effects and especially hydroxamic acid based inhibitors lack good pharmacokinetic profiles. Therefore, the development of isoform-selective non-hydroxamic acid HDAC inhibitors is a highly regarded field in medicinal chemistry. In this study, we analyzed different ligand-based and structure-based drug design techniques to predict the binding mode and inhibitory activity of recently developed alkylhydrazide HDAC inhibitors. Alkylhydrazides have recently attracted more attention as they have shown promising effects in various cancer cell lines. In this work, pharmacophore models and atom-based quantitative structure-activity relationship (QSAR) models were generated and evaluated. The binding mode of the studied compounds was determined using molecular docking as well as molecular dynamics simulations and compared with known crystal structures. Calculated free energies of binding were also considered to generate QSAR models. The models created show a good explanation of in vitro data and were used to develop novel HDAC3 inhibitors.

Pharmacophores are an established concept for the modelling of ligand-receptor interactions based on the abstract representations of stereoelectronic molecular features. They became widely popular as filters for the fast virtual screening of large compound libraries. Until today a lot of effort has been put into the development of sophisticated algorithms and strategies to increase the computational efficiency of the screening process. However, hardly any focus was put on the development of automated procedures that optimise pharmacophores towards higher discriminatory power, which until today still has to be done manually by a human expert. In the age of machine learning, the researcher has become the decision-maker at the top level, outsourcing analysis tasks and recurrent work to advanced algorithms and automation workflows. Here we propose an algorithm for the automated selection of features driving pharmacophore model quality using SAR information extracted from validated QPhAR models. By integrating the developed method into an end-to-end workflow, we present a fully automated method that is able to derive best-quality pharmacophores from a given input dataset. Finally, we show how the QPhAR-generated models can be used to guide the researcher with insights regarding (un-)favourable interactions for compounds of interest.

Although nanotechnology is a new and rapidly growing area of science, the impact of nanomaterials on living organisms is unknown in many aspects. In this regard it is extremely important to perform toxicological tests, but complete characterization of all varying preparations is extremely laborious. The computational technique called quantitative structure-activity relationship, or QSAR, allows reducing the cost of time- and resource-consuming nanotoxicity tests. In this review, (Q)SAR cytotoxicity studies of the past decade are systematically considered. We regard here five classes of engineered nanomaterials (ENMs): metal oxides, metal-containing nanoparticles, multi-walled carbon nanotubes, fullerenes, and silica nanoparticles. Some studies reveal that QSAR models are better than classification SAR models, while other reports conclude that SAR is more precise than QSAR. The quasi-QSAR method appears to be the most promising tool, as it allows accurately taking experimental conditions into account. However, experimental artifacts are a major concern in this case

In the bioprinting process, controlling the motion of bioprinters involves a computer-aided design (CAD) model, converting that model into g-code, and transmitting the motion commands to the bioprinters. The g-code file contains information about the motion of the axes and can be generated using various software. However, a challenge arises when using g-code between different bioprinters. Therefore, the objective of this study was to propose a reliable method for analyzing the differences in 3D bioprinting devices by parameterizing a crucial variable for extrusion bioprinting: the E-value. Four bioprinters from three different manufacturers were used to investigate the extrusion behavior when subjected to the same E-value.

Three-dimensional (3D) printing technology, also known as additive manufacturing (AM), has emerged as an attractive state-of-the-art tool for precisely fabricating functional materials with complex geometries, championing several advancements in tissue engineering, regenerative medicine, and therapeutics. However, this technology has an untapped potential for biotechnological applications, such as sensor and biosensor development. By exploring these avenues, the scope of 3D printing technology can be expanded and pave the way for groundbreaking innovations in the biotechnology field. Indeed, new printing materials and printers would offer new possibilities for seamlessly incorporating biological functionalities within the growing 3D scaffolds. Herein, we review the extrusion-based 3D printing modalities emphasizing biosensor applications. We highlighted the application of natural, synthetic, and composite biomaterials as 3D-printed soft hydrogels. Emphasis was placed on the approach by which the sensing molecules were introduced during the fabrication process. Finally, the future perspective was provided.

Synthesis of heterodinuclear 3d transition metal complexes in which two metal ions are introduced in equivalent coordination sites of a ligand is quite uncommon. We have previously shown that the application of the cis-trans isomerization of the oxamido group was able to furnish such a possibility. In the present paper we demonstrate that this synthetic pathway, relying on the possibility of changing the conformation (cis vs trans) of the oxamido group, can be extended to other ligands. Although we have not been able to structurally characterize these complexes, EPR and magnetic data do confirm the efficiency of this reaction pathway. We also demonstrate that the cis-trans isomerization of the oxamido group is not due to a particular property of the ion involved in the reaction. In fact, isomerization is governed by the basicity of the reaction medium. According to the reaction condition, it is possible to favor or not this phenomenon, and to increase the accessibility to a larger number of novel genuine complexes. But the oxophilic character of the lanthanide ions impedes this isomerization in 3d-4f complexes. The very weak magnetic interactions observed in these Cu-Gd complexes can be explained thanks to spin polarization.

Based on three-dimensional optical proximity correction (3D OPC), recent advancements in 3D lithography have enabled the high-fidelity customization of 3D micro-optical elements. However, micron-to-millimeter scale structures represented by Fresnel lens design bring more stringent requirements for 3D OPC, which poses significant challenges to the accuracy of models and the efficiency of algorithms. Thus, a lithographic model based on optical imaging and photo-chemical reaction curve is developed in this paper, and a sub-domain division method with a statistics principle is proposed to improve the efficiency and accuracy of 3D OPC. Both the simulation and the experimental results showed the superiority of the proposed 3D OPC method in the fabrication of the Fresnel lenses. The computation memory requirements of the 3D OPC are reduced to below 1 %, and the profile error of the fabricated Fresnel lens reduced 79.98%. Applying the Fresnel lenses to an imaging system, the average peak signal to noise ratio (PSNR) of the image increased by 18.92 %, and the average contrast of the image enhanced by 36 %. We believe the proposed 3D OPC method can be extended to the fabrication of vision-correcting ophthalmological lenses.

: Introduction: Discovering compounds with antibacterial activity is crucial in the current fight against antibiotic-resistance. Material and Methods: We generate two QSAR model to design six new heteroaryl drug candidates; we assessed the antibacterial properties of the compounds against nine ATCC strains, the majority being part of the ESKAPE group, that include Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and also Salmonella enterica and Escherichia coli. We performed a synergic assay in which we combined PB4, a compound that we have previously tested in published studies, with GC-VI-70, one of the new compounds with the best cytotoxicity/MIC profile. We tested sub-MIC concentrations of PB4 with five antibiotics (linezolid, gentamycin, ampicillin, erythromycin, rifampin and imipenem) to examine the synergic effect on the ATCC strains. To evaluate compounds’ cytotoxicity, we performed a 24-hour and 48-hour 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on Colorectal Adenocarcinoma (CaCo-2) cells. The antibiotics were tested, alone and in combination with PB4. Results: PB4 lowered the MIC measured for GC-VI-70 and for the various antibiotics employed in clinical use, and all the compounds presented in this study have cytotoxic activity against cells. Conclusions: These compounds show promising use in combination with antibiotics to improve their effectiveness at low concentrations, to prevent unwanted cytotoxic effects.

Pseudomonas aeruginosa is a Gram-negative bacillus included among the six "ESKAPE" microbial species with an outstanding ability to "escape" currently used antibiotics and developing new antibiotics against it is of the highest priority. Whereas minimum inhibitory concentration (MIC) values against Pseudomonas aeruginosa have been used previously for QSAR model development, disk diffusion results (inhibition zones) have not been apparently used for this purpose in the literature, and we decided to explore their use in this sense. We developed multiple QSAR methods using several machine learning algorithms (Support vector classifier, K Nearest Neighbors, Random Forest Classifier, Decision Tree Classifier, AdaBoost Classifier, Logistic Regression, and Naive Bayes Classifier). The main descriptors used in building the models belonged to the families of adjacency matrix, constitutional descriptors, first highest eigenvalue of Burden matrix, centered Moreau-Broto autocorrelation, and averaged and centered Moreau-Broto autocorrelation descriptors. A total of 32 models were built, of which 28 were selected and stacked to create a meta-model. In terms of balanced accuracy, the best performance was provided by KNN, SVM and AdaBoost algorithms, but the ensemble method had slightly superior results in nested cross-validation.

Drug induced liver injury (DILI) remains one of the challenges in the safety profile of both authorized drugs and candidate drugs and predicting hepatotoxicity from the chemical structure of a substance remains a challenge worth pursuing, being also coherent with the current tendency for replacing non-clinical tests with in vitro or in silico alternatives. In 2016 a group of researchers from FDA published an improved annotated list of drugs with respect to their DILI risk, constituting “the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans”, DILIrank. This paper is one of the few attempting to predict liver toxicity using the DILIrank dataset. Molecular descriptors were computed with the Dragon 7.0 software, and a variety of feature selection and machine learning algorithms were implemented in the R computing environment. Nested (double) cross-validation was used to externally validate the models selected. A number of 78 models with reasonable performance have been selected and stacked through several approaches, including the building of multiple meta-models. The performance of the stacked models was slightly superior to other models published. The models were applied in a virtual screening exercise on over 100,000 compounds from the ZINC database and about 20% of them were predicted to be non-hepatotoxic.

While Neural Radiance Fields (NeRF) are gaining increasing interest in various domains as innovative methods for novel view synthesis and image-based reconstruction, their potential application in the realm of Cultural Heritage remains unexplored. Purpose of this paper is to assess the effectiveness of applying NeRF to sets of images of digital heritage objects and sites. The study’s findings demonstrate that NeRF could be valuable when used in combination with or as a comparison to other well-established techniques such as photogrammetry, to expand the possibilities of preserving and presenting heritage assets with enhanced visual fidelity and accuracy. Particularly, NeRF show promising results in improving the rendering of translucent and reflective surfaces, objects with homogeneous textures, and elements with intricate details. In addition, we demonstrate that, when considering the same set of input images (with known camera poses), reducing the image quality or the number of images results in significantly less information loss with NeRF compared to photogrammetry. This suggests that NeRF is preferentially suited for scenarios involving sparse information or low-quality photos or videos, which could be especially valuable in risky or challenging situations.

3D printing is playing an important role in cardiovascular disease by use of personalised models with replication of normal anatomy and pathology with high accuracy and reliability. While 3D printed heart and vascular models are shown to improve medical education, preoperative planning and simulation of cardiac procedures, and enhance communication with patients, 3D bioprinting however, represents a potential advancement of 3D printing technology by printing cellular or biological components, functional tissues and organs that can be used in a variety of applications in cardiovascular disease. Recent advances in bioprinting technology have shown the ability to support vascularisation of large scale constructs with enhanced biocompatibility and structural stability, thus creating opportunities to replace damaged tissues or organs. In this review, we provide an overview of the use of 3D bioprinting in cardiovascular disease with a focus on technologies and applications in cardiac tissues, vascular constructs and grafts, heart valves and myocardium. Limitations and future research directions are highlighted.

Tumor cells evolve in a complex and heterogeneous environment composed of different cell types and an extracellular matrix. Current 2D culture methods are very limited in their ability to mimic the cancer cell environment. In recent years, various 3D models of cancer cells have been developed, notably in the form of spheroids/organoids, using scaffold or cancer-on-chip devices. However, these models have the disadvantage of not being able to precisely control the organization of multiple cell types in complex architecture and are sometimes not very reproducible in their production, and this is especially true for spheroids. Three-dimensional bioprinting can produce complex, multi-cellular, and reproducible constructs in which the matrix composition and rigidity can be adapted locally or globally to the tumor model studied. For these reasons, 3D bioprinting seems to be the technique of choice to mimic the tumor microenvironment in vivo as closely as possible. In this review, we discuss different 3D-bioprinting technologies, including bioinks and crosslinkers that can be used for in vitro cancer models, and the techniques used to study cells grown in hydrogels; finally, we provide some applications of bioprinted cancer models.

Background: The main objective of this study is to develop a customized metatarsophalangeal implant for the treatment of various conditions affecting this specific joint. This approach involves replacing the joint with a custom implant designed specifically to fit each patient's unique anatomical structure. The need for custom implants stems from the obvious lack of size variety available, which presents a major challenge when, the search for the ideal size implant can be a hard task, also when considering the possibility of extensive modification of the bone to adapt it to the available implant. This adaptation, often synonymous with bone reduction, can cause significant post-operative pain for the patient and impact healing time. Methods: A comparative study of modeling software was carried out to select the perfect software, by defining and comparing the relevant criteria. Similarly, the different biomaterial options were examined and compared to select the one best suited to this project, mentioning the imaging modality used to determine the types of images used for our approach. Finally, the 3D printers used in this work were represented, highlighting their technical characteristics. Findings: A resin metatarsophalangeal implant prototype was created using 3D modeling and reconstruction software and tools. Interpretation: Reconstruction and 3D modeling techniques are revolutionizing implant creation, offering customized solutions for patients suffering from metatarsophalangeal joint disorders caused by a wide range of diseases. These results have significant implications for disability management and rehabilitation, encouraging further exploration and progress.

Many agonists for the estrogen receptor are known to disrupt endocrine functioning. We have developed a computational model that predicts agonists for the estrogen receptor ligand-binding domain in an assay system. Our model was entered into the Tox21 Data Challenge 2014, a computational toxicology competition organized by the National Center for Advancing Translational Sciences. This competition aims to find high-performance predictive models for various adverse-outcome pathways, including the estrogen receptor. Our predictive model, which is based on the random forest method, delivered the best performance in its competition category. In the current study, the predictive performance of the random forest models was improved by strictly adjusting the hyperparameters to avoid overfitting. The random forest models were optimized from 4,000 descriptors simultaneously applied to 10,000 activity assay results for the estrogen receptor ligand-binding domain, which have been measured and compiled by Tox21. At this time, our model delivers the highest predictive power on estrogen receptor agonists in the world. Furthermore, analysis of the optimized model revealed some important features of the agonists, such as the number of hydroxyl groups in the molecules.

In this study, a simple machine learning-based quantitative structure-activity relationship (QSAR) model was developed to predict the inhibitory potency (pIC50 values) of FLT3 tyrosine kinase inhibitors, pivotal in treating Acute Myeloid Leukemia (AML). Distinctively, our model leverages an extensive and diverse dataset, 14 times larger than those employed in prior studies within this field, enabling an unparalleled scope of compound analysis. This vast dataset, combined with further exploration of molecular descriptors, enabled predictions of extraordinary precision, covering a broader spectrum of FLT3 inhibitors than was previously possible. The Random Forest Regressor (RFR) algorithm, selected for its superior predictive performance, was trained with 1080 inputs and validated through comprehensive external and internal methods. It achieved an remarkable coefficient of determination (R^2) of 0.941 and a standard deviation of 0.235 on a test set of 270 compounds, highlighting the efficacy of model in predicting FLT3 inhibitory activity. Key molecular descriptors were identified, enhancing our understanding of structural requirements for inhibitor potency. Additionally, we developed a user-friendly computational tool that enables the rapid prediction of pIC50 values. Utilizing this tool, potential FLT3 inhibitors were identified through ligand-based virtual screening. This study represents a major advancement in FLT3 inhibitor discovery by utilizing a simple QSAR-machine learning model. It enables more efficient and precise identification of potential drug candidates at an early stage, promising a faster development of targeted therapies and streamlining the ligand-based drug design process.

Background: The development and application of machine learning (ML) methods became so fast that almost nobody can follow their developments in every detail. There is no wonder that numerous errors and inconsistencies in their usage have also spread with a similar speed independently from the tasks: regression and classification.. This work summarizes frequent errors committed by certain authors with the aims of helping scientists to avoid them. Methods: The principle of parsimony governs the train of thought. Fair method comparison methods can be completed with multicriteria decision making techniques, preferably sum of ranking differences (SRD). Its coupling with analysis of variance (ANOVA) decomposes the effect of several factors. Earlier findings are summarized in a review-like manner: the abuse of the correlation coefficient and proper practices for model discrimination are also outlined. Results: Using an illustrative example, the correct practice and the methodology is summarized as guidelines for model discrimination, and for minimizing the prediction errors. The following factors are all prerequisites for successful modeling: proper data preprocessing, statistical tests, suitable performance parameters, appropriate degrees of freedom, fair comparison of models, outlier detection, just to name a few. A checklist is provided on how to present ML modeling properly. The advocated practices are reviewed in the discussion. Conclusions: Many of the errors can easily be filtered out with careful reviewing. The authors’ responsibility is to adhere to the rules of modeling and validation.

Manufacturing of facial epithesis is a complex technological process including several traditional stages of production, accompanied by aggravated psycho-emotional status of the patient. One of the main factors causing discomfort in patients with facial defects is the process of obtaining silicone impressions from the wound surface and the long waiting period for the final epithesis. Active development of digital technologies in medicine and dentistry helps specialists not only to automate most of the traditional stages of manufacturing of dento-mandibular and facial prostheses, but also improves the quality of life of patients by increasing the efficiency of services and reducing the production time of prosthetic structures. The application of digital technologies in the production of facial epithesis was difficult due to the lack of specialized 3D-software for modeling and material for further additive manufacturing of structures. The authors developed a unique technology for 3D modeling and additive manufacturing of facial epithesis, including a 3D CAD module and material for 3D printing. The primary objective was to fabricate immediate facial prostheses in the postoperative period in the shortest possible time until the final epithesis was fabricated.

The present study aimed to characterize the microstructure of a temporary 3D printing resin (Resilab Temp), evaluating the optical properties and mechanical behavior according to different post-processing curing times. For the analysis of the surface microstructure and establishment of the best printing pattern, samples in bar format following ISO 4049 (25 x 10 x 3 mm) were designed in CAD software (Rhinoceros 6.0), printed on the W3D printer (Wilcos), and light-cured in Anycubic Photon at different times (without curing, 16 minutes, 32 minutes, and 1 hour). For the structural characterization, analyses were carried out in FTIR (Fourier Transform Infrared Spectroscopy) and Scanning Electron Microscopy (SEM). The mechanical behavior of the resin was based on flexural strength tests and Knoop microhardness. Color and translucency analysis were performed with a spectrophotometer (VITA Easy Shade Advanced 4.0), which was evaluated following CIELab, using gray, black, and white backgrounds. All analyses were performed immediately after making the samples and repeated after thermal aging with 2 thousand cycles (5-55 °C). The results obtained were statistically analyzed with a significance level of 5%. FT-IR analysis showed about a 46% degree of conversion on the surface and 37% in the center of the resin sample. The flexural strength was higher for the groups polymerized for 32 min and 1h, while the Knoop microhardness did not show a statistical difference between the groups. Color and translucency analysis also did not show statistical differences between groups. According to all the analyses carried out in this study, for the evaluated material, the post-polymerization time of 1 hour can be suggested to improve the mechanical performance of 3D-printed devices.

In recent years, Additive Manufacturing (AM), commonly referred to as 3D printing, has garnered the attention of the scientific community due to its capacity to transform ordinary and traditional items into customized materials at an affordable cost, through various AM processes. Antimicrobial/antibiofilm 3D printed materials are one of the most trending research topics, owing to the growing concerns over the emergence of complex microbial structures called "biofilms" on various surfaces. The review provides an overview of the evolution of additive manufacturing (AM) technologies and their various derivatives, along with a brief description of their materials and applications. It also introduces how biofilms can represent an advantageous lifestyle for microbial populations. The primary objective of this research was to conduct a systematic review on the development of planctonic or biofilm forms of microorganisms on 3D printed materials. The article summarizes commonly studied microorganisms on these materials and presents their 3D printing process, materials, as well as the fields covered by each of the analyzed papers. To the best of our knowledge, this is the first all-inclusive systematic review that amalgamated research conducted in diverse fields to assess the development of biofilms on surfaces produced through three-dimensional printing. Most notably, this review presents a comprehensive account of sustainable approaches for producing antimicrobial materials through 3D printing. Additionally, we assess their advancements in various fields such as medicine, environment, agri-food, and other relevant sectors. The findings of our literature review can be used to recommend appropriate microorganisms, 3D printing materials, and technologies for academic and industrial research purposes focusing on the development of microbial biofilms on 3D printed surfaces. Furthermore, it highlights the potential of environmentally-friendly modified AM technologies to combat biofilms in clinical and non-clinical areas. Our goal with this review is to help readers gain a better understanding of fundamental concepts, inspire new researchers, and provide valuable insights for future empirical studies focused on eradicating biofilms from 3D printed materials.

This research discusses the development of a software-centered EdTech (Education Technology) class model through the implementation of a course titled "3D Time Machine" at a 4-year university in Republic of Korea over two semesters. The course focused on teaching 3D modeling software, Blender, within the history department. The primary objective of offering this course was to equip students from the digital generation with the capability to manipulate digital technology effectively. Through studying historical materials and accumulating domain knowledge, students could construct their narratives from their unique perspectives. This aimed to foster their proficiency in digital technology operation, preparing them for an education environment increasingly centered around virtual worlds. As the use of virtual worlds gains prominence in educational settings, there is a growing need to incorporate curricula that prepare students to thrive as well-prepared citizens in future societies. Assessing the digital competencies of contemporary university students and designing instructional models with particular attention to their needs is becoming increasingly important. This research draws insights from interviews, conducted in both face-to-face and written formats, with students who participated in the "3D Time Machine" course. The interviews revealed valuable insights that can be actively incorporated into the development of software-centered EdTech instructional models. They reported that they expanded their perceptions as they learned how to make their ideas tangible. The course helped students overcome their fear of digital technology. In conclusion, the course effectively employs 3D modeling technology, a software-centered EdTech, as a core element in helping students develop their narratives rapidly and diversely, thereby playing a crucial role in their ability to articulate their unique perspectives.

Pure monocular 3D reconstruction is an ill-posed problem that has attracted the research community's interest due to the affordability and availability of RGB sensors. SLAM, VO, and SFM are disciplines formulated to solve the 3D reconstruction problem and estimate the camera’s ego-motion, so many methods have been proposed. However, most of these methods were not evaluated in large datasets, under various motion patterns, had not been tested under the same metrics, and most of them had not been evaluated following a taxonomy, making their comparison and selection difficult. In this research, we performed a comparison of ten publicly available SLAM and VO methods following a taxonomy, including one method for each category of the primary taxonomy, three machine learning-based methods, and two updates of the best methods, to identify the advantages and limitations of each category of the taxonomy and test if the addition of machine learning or the updates made on those methods improved them significantly. Thus, we evaluated each algorithm under the TUM-Mono benchmark and performed an inferential statistical analysis to identify significative differences through its metrics. Results determined that sparse-direct methods significantly outperformed the rest of the taxonomy, and fusing them with machine learning techniques significantly improves the performance of geometric-based methods from different perspectives.

Most common classifications for acetabular bone defects are based on radiographic two-dimension imaging, with low reliability and reproducibility. With the rise of modern processing techniques based on 3D modelling, methodologies for volumetric quantification of acetabular bone loss are available. Our study aims to describe a new methodology for quantitative assess-ment of acetabular defects, based on 3D modelling, focused on the surface analysis of the integrity of the main anatomical structures of the acetabulum represented by four corresponding sectors (posterior, superior, anterior, and medial). The defect entity is measured as the Area Increase Ra-tio (AIR) detected in all the sectors analyzed on three planes of view (frontal, sagittal and axial) compared to healthy hemipelvises. The analysis was performed on 3D-models from the CT-scan of six exemplary specimens with a unilateral pathological hemipelvis. AIR between the native and the pathological hemipelvis was calculated for each sector, for a total of 48 analysis (range, +0.93% - +171.35%). AIR of >50% were found in 22/48(45.8%) sectors and affected mostly the posterior, medial and superior sectors (20/22, 90.9%). Qualitative analysis showed consistency of the data with the morphological features of the defects. Further studies with larger samples are needed to validate the methodology and potentially develop a new classification scheme.

In the last 20 years, TADs have become one of the topics in orthodontic science, as it becomes one of the effective anchorages in moving teeth in a 3D movement to treat malocclusion and dental-alveolar orthopedic. Problems with the collusion of the roots of the teeth and trauma have hindered the use of these TADs; one of the solutions to keep TADs safe is a step-by-step innovation of procedure to make this anchorage concept using TAD safe. Making surgical guides for single-standing TADs is essential, and in practice, it is virtually possible with the advance of today's CAD/CAM and 3D printers. The content subject in the paper contains two parts: the consideration of why a surgical guide is necessary for the implantation of TADs and the making of the Surgical guide itself.

In this study, we designed a functional neuro-cardiac model to help us examine the role of neuronal regulation and confirm the importance of neural innervation techniques for cardiac tissue regeneration. A three-dimensional (3D) bioprinted neuro-cardiac scaffold composed of a mixture of gelatin-alginate and alginate-genipin-fibrin hydrogels was developed with a 2:1 ratio of AC16 cardiomyocytes (CMs) and retinoic acid differentiated SH-SY5Y neuronal cells (NCs) respectively. A unique semi-3D bioprinting approach was adopted where the CMs were mixed in the cardiac bioink and printed using an anisotropic accordion design to mimic the physiological tissue architecture in vivo. The voids in this 3D structure were methodically filled in using a NCs-gel mixture and cross-linked. Confocal fluorescent imaging using Microtubule-associated protein 2 (MAP-2) antibodies for labeling NCs, and the MyoD1 antibody for CMs revealed functional coupling between the two cell types in the final cross-linked structure. This data confirmed the development of a physiologically functional neuro-cardiac model that can be used to study neuro-cardiac modulation under physiological and pathological conditions.

In recent years, with the development of social media, people are more and more inclined to upload text, pictures and videos on the platform to express their personal emotions, thus the number of short videos is increasing and becoming the first choice for people to socialize. Unlike the traditional way, people can convey their personal emotions and opinions through media other than words, such as video images, etc. for external information. Therefore, the expression and analysis of emotions is not only through text, but also through the analysis of emotional needs in images and videos, and the research scholars have customized products for individual users. Compared with pure text content, video information can more intuitively express users' happiness, anger and sorrow, thus short video-related applications have gained more and more popularity among Internet users in recent years. However, not all short videos on social networking sites can accurately express users' emotions, and related text information can more accurately assist sentiment analysis and thus improve accuracy. However, short video sentiment analysis based on video frame images is inaccurate in some scenarios, such as when expressing tears of joy, the sentiment expressed by the user's facial expression and voice are different, which will cause errors in the analysis of sentiment. As a result, researchers began to consider multimodal sentiment analysis to reduce the impact of the above scenarios on short video sentiment analysis. This paper focuses on proposing a sentiment analysis method for short videos. We first propose a residual attention model to make full use of the information in audio to classify the emotions contained in them. Then the text information in the dataset is classified by feature extraction. The key to extract features from text information is not only to retain the semantic information of the text, but also to explore the potential emotional information in the text, so as to ensure the integrity of the text information features. The experiments show that the sentiment analysis model proposed in this paper is more superior than the baselines.

An approach employing ultrafast laser hybrid subtractive-additive microfabrication combining ablation, 3D nanolithography and welding is proposed for the realization of Lab-On-Chip (LOC) device. Single amplified Yb:KGW fs-pulsed laser source is shown to be suitable for fabricating microgrooves in glass slabs, polymerization of fine-meshes filter out of hybrid organic-inorganic photopolymer SZ2080 inside them, and, lastly, sealing the whole chip with cover glass into a single monolithic piece. The created microfluidic device proved its particle sorting function by separating 1 μm and 10 μm polystyrene spheres in a mixture. All together, this shows that fs-laser microfabrication technology is a flexible and versatile tool for the manufacturing of mesoscale multi-material LOC devices.

Digital twins are gaining in popularity for simulating complex natural and urban environments. In this context, accurate segmentation of objects within 3D urban environments is of crucial importance. The aim of this project is to develop a methodology for extracting buildings from textured 3D meshes. To this end, PicassoNet-II, a semantic segmentation architecture is employed. The methodology also incorporates Markov field-based contextual analysis to assess post-segmentation features. In addition, building instantiation is performed using cluster analysis algorithms. Training this model to fit various datasets requires a large amount of annotated data, both from Quebec City, Canada, and from simulated data. Experimental results show that the use of simulated data improves segmentation accuracy, and the DBScan algorithm proves effective in extracting isolated buildings. This project paves the way for improved applications in 3D urban modeling, offering opportunities in fields ranging from urban planning to resource management. The positive results with simulated data reinforce the impact of this research on improving digital models of our ever-changing urban environments.

3D Zernike moments based on 3D Zernike polynomials have been successfully applied to the field of voxelized 3D shape retrieval and have attracted more attention in biomedical image processing. As the order of 3D Zernike moments increases, both computational efficiency and numerical accuracy decrease. Due to this phenomenon, a more efficient and stable method for computing high-order 3D Zernike moments was proposed in this study. The proposed recursive formula for computing 3D Zernike radial polynomials combines the recursive calculation of spherical harmonics to develop a voxel-based algorithm for the calculation of 3D Zernike moments. The algorithm was applied to the 3D shape Michelangelo's David with a size of 150×150×150 voxels. As compared to the method without additional acceleration, the proposed method uses a group action of order sixteen orthogonal group and saving unnecessary iterations, the factor of speed-up is 56.783±3.999 when the order of Zernike moments is between 10 and 450. The proposed method also obtained an accurate reconstructed shape with the error rate (normalized mean square error) of 0.00 (4.17×10^-3) when the reconstruction was computed for all moments up to order 450.

This paper aims to present the method of producing visual media for communicating the Asinara Island National Park plan. These products are landscape visualizations able to foster landscape preservation both from the point of view of the management of the landscape and of the citizen's involvement in the communication of the historical and environmental values of the landscape. Starting from landscape information gathering, the research has experimented with an operative method for processing different graphic representations from the same geographic database, calibrating the outputs to different audiences, their needs, objectives, and literacy skills. Three different types of products are presented: the first is a digital, dynamic and multisectoral decision-making GIS tool for park management. The second is a 3D model, aimed to the virtual fruition. The third is a map of the zoning park plan drawn to be easily readable to the non-expert public. This case study emerges as a replicable method to process the landscape information to make different visualization tools from a single geographic model, to meet the different requirements that arise from a complex landscape planning process.

New in vitro approaches for the assessment of their toxicity are crucial for creating better risk assessments given the growing use of nanoparticles (NPs) in the production of consumer goods. Humans will be exposed to nanoparticles through the inhalation route from contaminated aerosol. A promising method for evaluating the genotoxicity of NPs in vitro uses human airway epithelial cells. This study aimed to determine whether there were differences in morphology change of human bronchial/tracheal epithelial (HBTEC) cells responded to NPs in 2D and 3D spheroid models and to evaluate genotoxicity in 2D and 3D cultures after 24 hr exposure to TiO2-, Ag- and ZnO-NPs using the comet assay. Our 2D and 3D HBTEC cultures with TiO2-NPs did not show any statistically significant genotoxicity compared to controls for concentration points tested in vitro. HBTEC cells grown as 2D indicated that exposure to ZnO-NPs at low concentrations (10-50 ug/mL) for 24 hr did not cause any genotoxic effect but, at high concentrations, genotoxicity was observed. In contrast, treatment of 2D HBTEC with AgO-NPs led to an elevated in percentage of tail DNA damage from 50 ug/mL to 100 ug/mL, which was concentra-tion-dependent. Using 3D spheroid assays revealed a lower %tail length in ZnO- and AgO-NPs, thus exhibiting in vitro genotoxicity of NPs in this cell model. Spheroids (3D) rather than mono-layer cultures (2D) are believed to more precisely represent in vivo-like cell behavior when evaluating genotoxicity. Together, our findings demonstrate the genotoxic effects of NPs and point to the critical role that cell culture models play in the evaluation of toxicological risk.

In the production of green parts from powder, there is unavoidable slight deviation in the die filling, even when high-quality powders are used. The quantity of powder in the die varies and thus affects the weight of the compact. This filling variation results in variation of the pressing force, and thus influences the part geometry. The development of the DORST Netshape® System was conceived as an autonomous manufacturing system in order to compensate for these effects. Based on the Dorst Industry 4.0 innovations for part weight measuring immediately after pressing in combination with a laser dimension measuring system, this technology package attempts to reach enhanced precision and consistency in production. The paper presents results from various trials that show the capability of this new system, designed to improve the quality of pressed parts.

This paper presents the results of the investigation of composite sinters W-TiB2 which were used as an electrode in the process of electro-spark deposition (ESD) and the examination of the deposited layers. The scope of the study includes detailed characteristics of powder mixtures, composite sinters made using the spark plasma sintering method (SPS) and layers deposited in the electro-spark process. The ESD process, using the W+30 vol.% TiB2 electrode, was carried out using an automated device. The substrates were made of copper and aluminium. The topography analysis of the surfaces of the composite layer and the evaluation of their wear resistance properties are also presented. The analysis of the results of research showed the possibility to obtain, using the SPS method, composite materials of good quality, which can be used as electrodes in the ESD process. The obtained layers had increased wear resistance in relation to the substrate material.

We present progress in fast, high-resolution imaging, material classification, and fault detection using hyperspectral X-ray measurements. Classical X-ray CT approaches rely on data from many projection angles, resulting in long acquisition and reconstruction times. Additionally, conventional CT cannot distinguish between materials with similar densities. However, in additive manufacturing, the majority of materials used are known a priori. This knowledge allows to vastly reduce the data collected and increase the accuracy of fault detection. In this context, we propose an imaging method for non-destructive testing of materials based on the combination of spectral X-ray CT and discrete tomography. We explore the use of spectral X-ray attenuation models and measurements to recover the characteristic functions of materials in heterogeneous media with piece-wise uniform composition. We show by means of numerical simulation that using spectral measurements from a small number of angles, our approach can alleviate the typical deterioration of spatial resolution and the appearance of streaking artifacts.

Fatigue remains a challenge especially for high end metal AM parts and materials. From a design perspective, the fatigue limit of an AM solution can be improved upon by optimizing the manufacturing process for a certain material and part. In addition, improved accuracy of design methodologies aids in capturing the features critical for fatigue and quantifies their significance to desired part lifetime as well as providing a basis for their avoidance. In current work we present an overall concept merging thermomechanical process and powder bed solidification modeling to micromechanical analysis of fatigue of the resulting material microstructure. Material features critical to fatigue, particularly surface roughness, internal defects such as porosity and cracks and on the other hand inclusions, can be assessed directly on the basis of AM part microstructure with respect to the resulting fatigue limit. Case analyses consist of maraging steel and nickel alloys. The overall scheme provides a basis for optimization of metal AM solutions against fatigue and multiscale modeling founded basis for fatigue design.

Quality assurance has been one of the major challenges in laser-based additive manufacturing (AM) processes. This study proposes a novel process modeling methodology for layer-wise in-situ quality monitoring based on image series analysis. An image-based autoregressive (AR) model has been proposed based on the image registration function between consecutively observed thermal images. Image registration is used to extract melt pool location and orientation change between consecutive images, which contains sensing stability information. Subsequently, a Gaussian process model is used to characterize the spatial correlation within the error matrix. Finally, the extracted features from the aforementioned processes are jointly used for layer-wise quality monitoring. A case study of a thin wall fabrication by a Directed Laser Deposition (DLD) process is used to demonstrate the effectiveness of the proposed methodology.

Additive Manufacturing (AM) simplifies the fabrication of complex geometries. Its scope has rapidly expanded from the fabrication of pre-production visualization models to the manufacturing of end use parts driving the need for better part quality assurance in the additively manufactured parts. Machine learning (ML) is one of the promising techniques that can be used to achieve this goal. Current research in this field includes the use of supervised and unsupervised ML algorithms for quality control and prediction of mechanical properties of AM parts. This paper explores the applications of supervised learning algorithms - Support Vector Machines and Random Forests. Support vector machines provide high accuracy in classifying the data and is used to decide whether the final parts have the desired properties. Random Forests consist of an ensemble of decision trees capable of both classification and regression. This paper reviews the implementation of both algorithms and analyzes the research carried out on their applications in AM.

OBJECTIVE: Although 3D-printed anatomic models are not new to medicine, the high costs and lengthy production times entailed have limited their application. Our goal was developing a new and less costly 3D modeling method to depict organ-tumor relations at faster printing speeds. METHODS: We have devised a method of 3D modeling using DICOM images. Coordinates are extracted at a specified interval, connecting them to create mesh-work replicas. Adjacent constructs are depicted by density variations, showing anatomic targets (ie, tumors) in contrasting color. RESULTS: An array of organ solid-tumor models were printed via Fused Deposition Modeling 3D printer at significantly less cost ($0.05/cm3) and time expenditure (1.73 min/cm3; both, p<.001). Printed models helped promote visual appreciation of organ-tumor anatomy and adjacent tissues. Our mesh-work 3D thyroidal prototype reproduced glangular size/contour and tumor location, readily approximating the surgical specimen. CONCLUSIONS: This newly devised mesh-type 3D printing method may facilitate anatomic modeling for personalized care and improve patient awareness during informed surgical consent.

3D printing facilitates the straightforward construction of microchannels with complex three-dimensional architectures. Here, we demonstrate 3D-printed modular mixing components that operate on the basis of splitting and recombining fluid streams to decrease interstream diffusion length. These are compared to helical mixers that operate on the principle of chaotic advection.

It is time-consuming for acquiring complete data by fully phase encoding in two orthogonal directions along with one frequency encoding direction. Undersampling in the 3D k-space is promising in accelerating such 3D MRI process. Though 3D undersampling can be conducted according to predefined probability density, the density based method is not optimal. Because of the large amount of 3D data and computational cost, it is challenging to perform data-driven and learning-based 3D undersampling and subsequent 3D reconstruction. To tackle this challenge, this paper proposes a deep neural network called EEUR-Net, realized by optimizing specific undersampling patterns for the fully-sampled 3D k-space data. Innovatively, our undersampling algorithm employs an end-to-end deep learning approach to optimize phase encoding patterns and uses a 3D U-Net for image reconstruction of undersampled data. Through end-to-end training, we obtain an optimized 3D undersampling pattern, which significantly enhances the quality of the reconstructed image under the same acceleration factor. A series of experiments on a knee MRI dataset demonstrated that, in comparison to standard random uniform, radial, Poisson and equispaced Cartesian undersampling schemes, our end-to-end learned undersampling pattern considerably improves the reconstruction quality of undersampled MRI images.

Three-dimensional reconstruction plays an important role in assisting doctors and surgeons in diagnosing bone defects’ healing progress. Common three-dimensional reconstruction methods include surface and volume rendering. As the focus is on the shape of the bone, volume rendering is omitted. Many improvements have been made on surface rendering methods like Marching Cubes and Marching Tetrahedra, but not many on working towards real-time or near real-time surface rendering for large medical images, and studying the effects of different parameter settings for the improvements. Hence, in this study, an attempt towards near real-time surface rendering for large medical images is made. Different parameter values are experimented on to study their effect on reconstruction accuracy, reconstruction and rendering time, and the number of vertices and faces. The proposed improvement involving three-dimensional data smoothing with convolution kernel Gaussian size 0.5 and mesh simplification reduction factor of 0.1, is the best parameter value combination for achieving a good balance between high reconstruction accuracy, low total execution time, and a low number of vertices and faces. It has successfully increased the reconstruction accuracy by 0.0235%, decreased the total execution time by 69.81%, and decreased the number of vertices and faces by 86.57% and 86.61% respectively.

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.

3D printing is described as the third industrial revolution: its impact is global in industry and progresses every day in society. It presents a huge potential for ecology and evolution, sciences with a long tradition of inventing and creating objects for research, education and outreach. Its general principle as an additive manufacturing technique is relatively easy to understand: objects are created by adding material layers on top of each other. Although this may seem very straightforward on paper, it is much harder in the real world. Specific knowledge is indeed needed to successfully turn an idea into a real object, because of technical choices and limitations at each step of the implementation. This article aims at helping scientists to jump in the 3D printing revolution, by offering a hands-on guide to current 3D printing technology. We first give a brief overview of uses of 3D printing in ecology and evolution, then review the whole process of object creation, split into three steps: (1) obtaining the digital 3D model of the object of interest, (2) choosing the 3D printing technology and material best adapted to the requirements of its intended use, (3) pre- and post-processing the 3D object. We compare the main technologies available and their pros and cons according to the features and the use of the object to be printed. We give specific and key details in appendices, based on examples in ecology and evolution.

In the realm of modern drug discovery, the integration of chemoinformatics and quantitative structure-activity relationship (QSAR) modeling has emerged as a formidable alliance, enabling researchers to harness the vast potential of machine learning (ML) techniques for predictive molecular design and analysis. This review delves into the fundamental aspects of chemoinformatics, elucidating the intricate nature of chemical data and the crucial role of molecular descriptors in unveiling the underlying molecular properties. Molecular descriptors, including 2D fingerprints and topological indices, in conjunction with the structural-activity relationships (SARs), play a pivotal role in unlocking the pathway to small-molecule drug discovery. Technical intricacies of developing robust ML-QSAR models, including feature selection, model validation, and performance evaluation, are discussed herewith. Various ML algorithms, such as regression analysis and support vector machines, are showcased in the text for their ability to predict and comprehend the relationships between molecular structures and biological activities. This review serves as a comprehensive guide for researchers, providing an understanding of the synergy between chemoinformatics, QSAR, and ML. By embracing these cutting-edge technologies, predictive molecular analysis holds promise for expediting the discovery of novel therapeutic agents in the pharmaceutical sciences.

Topological indices have important role in theoretical chemistry for QSPR researches. Among the all topological indices the Randić and the Zagreb indices have been used more considerably than any other topological indices in chemical and mathematical literature. Most of the topological indices as in the Randić and the Zagreb indices are based on the degrees of the vertices of a connected graph. Recently novel two degree concepts have been defined in graph theory; ev-degrees and ve-degrees. In this study we define ev-degree Zagreb index, ve-degree Zagreb indices and ve-degree Randić index by using these new graph invariants as parallel to their corresponding classical degree versions. We compare these new group ev-degree and ve-degree indices with the other well-known and most used topological indices in literature such as; Wiener, Zagreb and Randić indices by modelling some physicochemical properties of octane isomers. We show that the ev-degree Zagreb index, the ve-degree Zagreb and the ve-degree Randić indices give better correlation than Wiener, Zagreb and Randić indices to predict the some specific physicochemical properties of octanes. We investigate the relations between the second Zagreb index and ev-degree and ve-degree Zagreb indices and some mathematical properties of ev-degree and ve-degree Zagreb indices.

We introduce optically clear and resilient free-form micro-optical of pure (non-photosensitized) organic-inorganic SZ2080 material made by femtosecond 3D laser lithography (3DLL). This is advantageous for rapid printing of 3D micro-/nanooptics, including their integration directly onto optical fibers. A systematic study on the fabrication peculiarities and quality of resultant structures is performed. Comparison of microlenses’ resiliency to CW and femtosecond pulsed exposure is determined. Experimental results prove that pure SZ2080 is ∼3 fold more resistant to high irradiance as compared with a standard photo-sensitized material and can sustain up to 1.91 GW/cm² intensity. 3DLL is a promising manufacturing approach for high-intensity micro-optics for emerging fields in astro-photonics and atto-second pulse generation. Additionally, pyrolysis is employed to shrink structures up to 40% by removing organic SZ2080 constituents. This opens a promising route towards downscaling photonic lattices and creation of mechanically robust glass-ceramic structures.

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.

Covid-19 is one of humanity’s biggest threat in the 21st century with WHO figures reporting 636 million cases and up to 6.6 million deaths globally. SARS-CoV-2, the virus that causes the Covid-19 disease, is characterized by high mutation which contributes to its rapid spread. While several vaccines have been produced to minimize the severity of the coronavirus and diverse treatment regimens have been approved by the US FDA under Emergency Use Authorization (EUA), SARS-CoV-2 viral mutations continue to derail the efforts of scientists as the emerging variants evade the recommended therapies. Nonetheless, diverse computational models exist that offer an opportunity to overcome the barriers involved in developing new drugs. In this review, the focus is on the use of various virtual screening techniques like molecular docking, molecular dynamics simulations, QSAR, pharmacophore modeling, and homology modeling in repurposing SARS-CoV-2 therapeutics. The results have been promising from the computer-aided drug design (CADD) studies in suggesting potential compounds for treatment of Covid-19 and helping in bringing the pandemic under control.

Plasmodium falciparum dihydroorotate dehydrogenase (PfDODH) is one of the enzymes currently explored in the treatment of malaria. Although there is currently no clinically approved drug targeting PfDODH, many of the compounds in clinical trials have [1, 2, 4,] triazolo [1, 5-a] pyrimidin-7-amine backbone structure. This study sought to design new compounds from the fragments of known experimental inhibitors of PfDODH. Nine experimental compounds retrieved from Drug Bank online were downloaded and broken into fragments using Schrodinger power shell; the fragments were recombined to generate new ligand structures using BREED algorithm. The new compounds were docked with PfDODH crystal structure, after which the compounds were filtered with extensive drug-likeness and toxicity parameters. A 2D-QSAR model was built using the multiple linear regression method and externally validated. The compounds electronic behaviours were studied using DFT calculations. Structural investigation of the six designed compounds, which had lower binding energies than the standard inhibitors, showed that five of them had [1, 2, 4,] triazolo [1, 5-a] pyrimidin-7-amine moieties and interacted with essential residues at the PfDODH binding site. In addition to their drug-like and pharmacokinetic properties, they also showed minimal toxicities. The externally validated 2D-QSAR model with R² and Q² values of 0.6852 and 0.6691, confirmed the inhibitory prowess of these compounds against PfDODH. The DFT calculations showed regions of the molecules prone to electrophilic and nucleophilic attack. The current study thus provides insight into the development of a new set of potent PfDODH inhibitors.

Path planning in 3D environment is a fundamental research area for robots and autonomous vehicles. Based on the principle ``the shortest path consists of tangents'', RimJump* is proposed as a tangent-based path planning method suitable for finding the shortest path (both off-ground and on-ground) in 3D space (e.g., octomap and point cloud) for mobile platform to follow. RimJump* searches the tangent graph in the form of a path tree and considers the geometrical properties of the locally shortest path. Therefore, the method can provide all of the locally shortest paths that connect the starting point and the target, including the globally shortest path. And the time cost of RimJump* is insensitive to map scale increases in comparison to methods that search the whole passable space rather than the surface of the obstacle, e.g., Dijkstra and A*. In the Results, RimJump* is compared with other methods in terms of path length and time cost.

Background: Melatonin is a potent mitochondrial, cytoprotective and antioxidant molecule with potentially strong anti-aging properties. Topical melatonin has shown to improve the clinical signs of skin aging. Melatosphere™ is a new lipid-based delivery system able to improve stability and skin penetration of melatonin when used in topical formulations. No clinical studies, using objective instrumental data, are available so far regarding the positive effect of Melatosphere™ in improving wrinkles in women with mild-to-moderate skin aging. Study Aim: We evaluate, in an open prospective, evaluator-blinded trial, the effects on skin texture of 2 months treatment with a Melatosphere™ based cream. Subjects and Methods: 15 women aged >45 years with mild to moderate facial skin aging (Glogau score ≥2) participated in the trial, after their informed consent. An ANTERA 3D computer-assisted skin analysis evaluation for the assessment of coarse and fine wrinkles of the periorbital area and melanin content was performed at baseline and after two months of treatment. An evaluator-blinded Investigator Global assessment of skin elastosis, roughness, level of dyscromia, skin dryness and presence of actinic damage was also performed at the same time points using a 4-grade score from 0 (no sign) to 3 (severe sign). Results: At baseline the mean (SD) IGA score was 8.2(1.0). After 2 months the IGA score significantly decrease to 4.2(1.4) (49% reduction) (P=0.0007). ANTERA 3D evaluations showed a significant reduction in skin coarse and fine wrinkles volume in the target area of -31% and -18%, respectively. Melanin content was reduced significantly by -17%. Conclusion: Topical melatonin carried in Melatosphere improves in the short-term signs of skin aging evaluated clinically and by ANTERA 3D device in women with mild to moderate skin aging.

We demonstrated a new approach to the production of three-dimensional-coated patterns using liquid route. Metallic perovskite oxides were coated onto three-dimensional (3D) microstructured substrates with different aspect ratios. The success of the method relies on the solution viscosity monitored by adding viscous liquid. The process of oxide thin films consists in three steps: preparing the precursor solution, coating the solution by spin-coating process onto three-dimensional-Si substrates and post-annealing. The chemical solution 3D-coating is conformal.

Prior to clinical trials, preclinical testing of oncology drug candidates is performed by evaluating drug candidates with in vitro and in vivo platforms. For in vivo testing, animal models are used to evaluate the toxicity and efficacy of drug candidates. However, animal models often display poor translational results as many drugs that pass preclinical testing fail when tested in humans, with oncology drugs exhibiting especially poor acceptance rates. The FDA Modernization Act 2.0 promotes alternative preclinical testing techniques, presenting the opportunity to use higher complexity in vitro models as an alternative to in vivo testing, including 3D cell culture models. 3D tissue cultures address many of the shortcomings of 2D cultures by more closely replicating the tumour microenvironment through a combination of realistic drug diffusion, paracrine signaling, cellular phenotype, and vascularization that can better mimic native human tissue. This review will discuss the common forms of 3D cell culture, including cell spheroids, organoids, organs-on-a-chip, and 3D bioprinted tissues. Their advantages and limitations will be presented, aiming to discuss the use of these 3D models to accurately represent human tissue and as an alternative to animal testing. The use of 3D culture platforms for preclinical drug development is expected to accelerate as these platforms continue to improve in complexity, reliability, and translational predictivity.

Transparent and high-hardness materials have become the object of wide interest. Most notably, it concerns technical glasses and crystals. A notable example is a sapphire – one of the most rigid materials having impressive mechanical stability and good optical properties. Nonetheless, using this material for 3D micro-fabrication is not straightforward due to its brittle nature. On the microscale, selective laser etching (SLE) technology is an appropriate approach for such media. Therefore, we present our research on c-cut crystalline sapphire microprocessing by using femtosecond radiation-induced SLE. Here we demonstrate a comparison between different wavelength radiation (1030 nm, 515 nm, 343 nm) usage for modification inscription and various etchants (Hydrofloridic acid, Sodium Hydroxide, Potassium Hydroxide and Sulphuric and Phosphoric acid mixture) comparison. We show that regular SLE etchants such as Hydrofluoric acid or Potassium Hydroxide are unsuitable materials for selective sapphire laser etching. Meanwhile, a 78% sulphuric and 22% phosphoric acid mixture at 270°C temperature is a good alternative for this process. We present the changes in the material after the separate processing steps. Finally, a protocol for advanced sapphire structure formation and a few exemplary structures are presented.

This paper analyses and evaluate the precision and the accuracy the capability of low-cost terrestrial photogrammetry by using many digital cameras to construct a 3D model of an object. To obtain the goal, a building façade has imaged by two inexpensive digital cameras such as Canon and Pentax camera. Bundle adjustment and image processing calculated by using Agisoft PhotScan software. Several factors will be included during this study, different cameras, and control points. Many photogrammetric point clouds will be generated. Their accuracy will be compared with some natural control points which collected by the laser total station of the same building. The cloud to cloud distance will be computed for different comparison 3D models to investigate different variables. The practical field experiment showed a spatial positioning reported by the investigated technique was between 2-4cm in the 3D coordinates of a façade. This accuracy is optimistic since the captured images were processed without any control points.

Fabrication of a true-3D inorganic ceramic with resolution down to nanoscale using sol-gel resist precursor is demonstrated. The method has an unrestricted free-form capability, control of the fill-factor, and high fabrication throughput. A systematic study of the proposed approach based on ultrafast laser 3D lithography of organic-inorganic hybrid sol-gel resin followed by a heat treatment enabled formation of inorganic amorphous and crystalline composites guided by the composition of the initial resin. The achieved resolution of 100 nm was obtained for 3D patterns of complex free-form architectures. Fabrication throughput of 50×10³ voxels/s is achieved; voxel - a single volume element was recorded by a single pulse exposure. After a subsequent thermal treatment, ceramic phase was formed depending on the temperature and duration of the heat treatment as validated by Raman micro-spectroscopy. The X-ray diffraction (XRD) revealed a gradual emergence of the crystalline phases at higher temperatures with a signature of cristobalite SiO₂, a high-temperature polymorph. Also, the tetragonal ZrO₂ phase known for its high fracture strength was observed. This 3D nano-sintering technique is scalable from nano- to millimeter dimensions and opens a conceptually novel route for optical 3D nano-printing of various crystalline inorganic materials defined by an initial composition for diverse applications for microdevices in harsh physical and chemical environments and high temperatures.

3D cell cultures have improved the evaluation of drugs for cancer therapy, due to their high similarity to solid tumors. In melanoma, autophagy appears to show a dual role depending on the progression of the disease. p62 protein has been proposed for the evaluation of autophagic flux since its expression is an indicator of the state of autophagy. Pentoxifylline (PTX) and Norcantharidin (NCTD) are drugs that have been shown to have anticancer effects in various types of cancer. In this work, B16F1 mouse melanoma cell line was used, from which two-dimensional (2D) monolayer cultures and three-dimensional (3D) organoids were carried out using the hanging drop technique. The expression of p62 was determined by western blot and immunofluorescences. Our results indicate that pentoxifylline reduces p62 expression in both types of culture. While Norcantharidin increases its expression in 3D cultures at 24 h. Therefore, these drugs could have a potential therapeutic use for the regulation of autophagy in melanoma, depending on the state of evolution of the disease.

Additive manufacturing, commonly referred to as 3D printing, is an exciting and versatile manufacturing technology that is gaining traction and interest in both academic and industrial settings. Polymeric materials are essential components in a majority of the “inks” used across the various 3D printing technologies. As the environmental ramifications of sole or primary reliance on petrochemicals as a resource for industrial polymers continue to manifest themselves at a global scale, a transition to more sustainable bioderived alternatives could offer solutions. In particular, cellulose is promising due to its global abundance, biodegradability, excellent thermal and mechanical properties, and ability to be chemically modified to suit various applications. Thus far, cellulose has typically been incorporated in additive manufacturing applications as a substrate, filler, or reinforcement for other materials. However, due to its versatility and desirable properties, the exploration of all-cellulose 3D printing materials and associated methodologies is increasing. This review will discuss the progress and status of all-cellulose 3D printing approaches, associated challenges, and their potential as a key player in a more sustainable industrial future.

This research presents the creation of a Virtual Reality experience for the Balzi Rossi museum, commemorating the centenary of Prince Albert I Grimaldi's archaeological work at the site. The project, a collaboration between the University of Genoa's 3D Lab Factory, Eurodrone, and the Balzi Rossi archaeological museum, aims to preserve and convey the site's heritage through advanced VR technology. Initially employing Unreal Engine 4, the team used photogrammetry for 3D reconstruction of the "Caviglione" and "Florestano" caves, notable for their ancient rock engravings. This first VR model, despite hardware limitations, provided an interactive exploration of the site. The subsequent development phase utilized Unreal Engine 5, incorporating Nanite technology for enhanced visual fidelity. This advancement resulted in a more detailed and immersive VR experience, presenting the Balzi Rossi cliff across different historical periods, including the Würm glaciation. Key to this phase was optimizing the VR experience for performance, focusing on stable frame rates and minimizing motion sickness, and integrating a multi-lingual interface for broader accessibility. Since November 2023, the VR setup at the Balzi Rossi Museum has been an educational and interactive feature, enabling visitors to explore the site's history virtually. This research demonstrates the potential of VR in cultural heritage preservation and education, providing a foundation for future technological improvements in the field.

When a limb suffers a fracture, rupture, or dislocation, it is traditionally immobilized with plaster. This may induce discomfort in the patient, excessive itching and sweating, which creates the growth of bacteria, leading to an unhygienic and difficulty to keep clean from treatment. Furthermore, if the plaster remains for a long period, it may cause lesions in the joints and ligaments. To overcome all these disadvantages, orthoses have emerged as important medical devices to help patients in rehabilitation, as well as for self-care of deficiencies in clinics and daily life. Traditionally, these devices are produced manually, which becomes time-consuming and error prone. From another point-of-view, it is possible to use imageology (X-ray or computed tomography) to scan the human body; a process that may help orthoses manufacturing but induces radiation to the patient. To overcome this great disadvantage, several types of 3D scanners, without any kind of radiation have emerged. This article describes the use of various types of scanners capable of digitizing the human body, to produce custom orthoses. Studies have shown that photogrammetry is the most used and most suitable 3D scanner for the acquisition of the human body in 3D. With this evolution of technology, it is possible to decrease the scanning time and it will be possible to introduce this technology in clinical environment.

Geotechnical investigation is an important site characterization process in engineering construction. Excavation pits and boreholes are popular geotechnical investigation methods for accessing subsurface soil and rock characteristics. Although they are accurate, they are limited to the discrete locations where tests are carried out. The demand for 3D representation has been increasing as an alternative for improved visualization of geotechnical investigations. This study developed a procedure for 3D modelling of geotechnical investigations using open-source software. It improves 3D visualization of geotechnical investigations and characterization of accuracy and uncertainty assessment. Presently, most geotechnical investigations do not regularly report uncertainty assessment despite its importance in risk analysis of the investigations. The procedure developed in this study was tested in a proposed site for construction of an Inland Container Depot where it depicted geotechnical soil properties with more than 80% accuracy on holdout samples. It was able to model both horizontal and vertical variations of the soil properties with quantification of uncertainty. More testing and wide applications are recommended.

Melanoma is a highly aggressive type of skin cancer produced by malignant transformation of melanocytes and it is usually associated with a poor prognosis. Clinically, melanoma has several stages associated with migration and invasion of the cells through the skin layers, rapid cell spreading and formation of tumors in multiple organs. The main problem is the emergence of resistance of melanoma to the applied methods of treatment, thus it is of primary importance to find more crucial signaling pathways that control the progression of this type of cancer and could be targeted to prevent melanoma spreading. The main life-threatening stage of melanoma is metastasis formation, and 3D cell spheroids are better suited for the study of this process. Using a combinative approach (RT-PCR, immunofluorescence, patch-clamp and calcium imaging) we showed the functional expression of mechanosensitive Piezo1 channels in SK-MEL-2 aggressive melanoma cell line. We found that chemical activation of Piezo1 by its selective agonist Yoda1 completely prevents melanoma spheroid formation, and could be considered as a novel approach for the prevention of melanoma development.

Free-edge effect is one of the factors affecting the mechanical properties of three-dimensional woven composites under tensile load. However, current research is relatively poorly understood regarding the effect of free-edge on the stiffness and strength of the material. This paper aims at examining the influence of free-edge effect on the mechanical properties of 3D woven composites under tension through experimental and simulation mathods. The three-dimensional DIC technique is used to collect the full-field strains on the specimen surface during the test, and the stress-strain differences in different regions in the width direction are analyzed, and the overlap of the curves in each region is found to be high. Experimental studies are conducted on specimens of different widths (within the range of 15-20 mm), and the results indicate that the differences in mechanical properties of 3D woven composites under tension loading in this width range are not significant. A progressive damage finite element model is developed for calculation and compared with experimental results.

The increased accessibility of drone technology and the wide use of Structure from Motion 3D scene reconstruction have transformed the approach for mapping inaccessible slopes undergoing active rockfalls. The Poggio Baldi landslide offers the possibility for many of these techniques to be deployed and integrated with the aim of defining a suitable workflow for the analysis of hazards in mountainous regions. The generation of multitemporal digital slope twins (2016 – 2019), informed a rockfall trajectory analysis that was carried out with a physical-based GIS model. We tested the rockfall scenario reconstructed and calibrated on the analysis of the rock mass characteristics and the geometrical and physical constraints given by the multi-temporal analysis of the SfM point clouds. This time-independent rockfall hazard analysis is a critical component to any subsequent holistic risk analysis on this case study, and any potential similar mountainous setting.

Beyond semantic segmentation,3D instance segmentation(a process to delineate objects of interest and also classifying the objects into a set of categories) is gaining more and more interest among researchers since numerous computer vision applications need accurate segmentation processes(autonomous driving, indoor navigation, and even virtual or augmented reality systems…) This paper gives an overview and a technical comparison of the existing deep learning architectures in handling unstructured Euclidean data for the rapidly developing 3D instance segmentation. First, the authors divide the 3D point clouds based instance segmentation techniques into two major categories which are proposal based methods and proposal free methods. Then, they also introduce and compare the most used datasets with regard to 3D instance segmentation. Furthermore, they compare and analyze these techniques performance (speed, accuracy, response to noise…). Finally, this paper provides a review of the possible future directions of deep learning for 3D sensor-based information and provides insight into the most promising areas for prospective research.

Polystyrene as a thin film on arbitrary substrates or pellets form defective graphene films or powders that can be dispersed in water and organic solvents. The materials were characterized by visible absorption, Raman and X-ray photoelectron spectroscopy, electron and atomic force microscopy and electrochemistry. Raman spectra of these materials show the presence of the expected 2D, G and D peaks at 2750, 1590 and 1350 cm^-1, respectively. The relative intensity of the G vs. the D peak is taken as a quantitative indicator of the density of defects in the G layer.

Osteoarthritis (OA) is a joint disease involving cartilage degeneration. This study aimed to compare properties of chondrocytes from less-affected (LA-Cartilage) and severely-affected (SA-Cartilage) of human OA articular cartilage. Based on Dougados classification, OA cartilage was classified into two groups; less-affected (Grade 0–1) and severely-affected (Grade 2–3). Chondrocytes from each group were cultured until passage (P) 4. Growth, migration, stem cell properties and chondrogenic properties under normal and inflammatory conditions, and the formation of in vitro 3D cartilage tissues were compared between groups. The growth and migratory properties of LA-chondrocytes and SA-chondrocytes were similar, except that the migration rate of SA-chondrocytes was significantly higher at P0 compared to LA-chondrocytes. Both LA-chondrocytes and SA-chondrocytes expressed mesenchymal stem cell markers and tri-lineage differentiation, but the expression of stem cell markers decreased significantly with increasing passage number. Exposure to inflammatory conditions induced distinct morphological changes and significant increases in expression of SOX9 at P4 and MMP3 at P1 for LA-chondrocytes. LA-chondrocytes and SA-chondrocytes able to develop into in vitro 3D constructs, but SA-chondrocytes exhibited superior cartilage-like properties. Chondrocytes from both less- and severely-affected regions are suitable to be used in clinical applications, however, chondrocytes from severely-affected regions could be a more favorable cell source.

Numerical weather prediction is an initial-value problem, for determination of the initial conditions, there are many methods and one of the most classical methods is variational methods in three dimensions, or 3D-Var. In this approach, with a defined cost function proportional to the square of the distance between the analysis and both the background and the observations, one can obtain the analysis. In the cost function, the background and the observations are reshaped to vectors; within this step, the order of the background error covariance matrix and the observational error covariance matrix becomes huge, which is not convenient to one to obtain the analysis. In this paper, according to the matrix analysis approach, we put forward some possible improvements to the dimension-reduction algorithm of 3D-Var, so that provide some references for data assimilation.

Background: Wilms tumor (WT) is the main renal tumor in children. SIOP-UMBRELLA Guidelines admit Nephron sparing surgery (NSS) in syndromic patients, and in small (&lt;300 ml) nonsyndromic unilateral WTs, without lymph node involvement, and with a substantial expected remnant renal function, after neoadjuvant chemotherapy. We report our prechemotherapy transperitoneal robot-assisted partial nephrectomy (RAPN) in a unilateral non-syndromic Wilms tumor. Methods: A 6-year-old-child showed an exophytic 3.6 cm diameter solid rounding mass involving the upper right renal pole at an incidental abdominal echotomography. CT-scan and abdominal MRI proved no local infiltration neither lymph node involvement was appreciated, suggesting an exophytic mass easily resectable through a NSS robotic approach, with a low risk of rupture and no subverted renal anatomy. The preoperative imaging was not suggestive for WT. A virtual 3D reconstruction of the tumor was performed. Results: the oncologic board approved a robot-assisted partial nephrectomy with the intraperitoneal approach. The histopathologic analysis displayed a WT. The patient underwent 10 vincristine-doses adjuvant chemotherapy. 28-months follow-up showed no tumor recurrence. Conclusions: Intraperitoneal RAPN can represent an opportunity for WT and needs to be assessed as a challenging possibility. This case suggests a potential role of prechemotherapy RAPN in the near future for highly selected patients.

In this paper, we present the idea of Self Supervised learning on the Shape Completion and Classification of point clouds. Most 3D shape completion pipelines utilize autoencoders to extract features from point clouds used in downstream tasks such as Classification, Segmentation, Detection, and other related applications. Our idea is to add Contrastive Learning into Auto-Encoders to learn both global and local feature representations of point clouds. We use a combination of Triplet Loss and Chamfer distance to learn global and local feature representations. To evaluate the performance of embeddings for Classification, we utilize the PointNet classifier. We also extend the number of classes to evaluate our model from 4 to 10 to show the generalization ability of learned features. Based on our results, embedding generated from the Contrastive autoencoder enhances Shape Completion and Classification performance from 84.2% to 84.9% of point clouds achieving the state-of-the-art results with 10 classes.

Electric energy has become essential nowadays not only for the daily life of each of us but also for the economy of different countries. The dissemination of geographic information plays an important role in national development as it facilitates communication between managers, investors, and consumers in this sector. Since the management of electricity network data was previously done in Tunisia based on paper maps and plans, the purpose of this article is to present a case of planning based on GIS, Web, and 3D Web GIS, which would have significant positive consequences on this sector from a technical and financial sides with an improvement in customer satisfaction and the creation of an intelligent electricity network which will be a real decision-making tool. This work draws up an inventory of the network MV (Medium Voltage)/LV (Low Voltage) of the region of Medjez El Bab which routes electricity to the big centers of consumption with access to MV/LV subscribers. The analysis of the network's impedance allowed carrying out different scenarios to optimize performance and obtain more realistic routes. Many thematic maps were produced as part of this project (Slope map, Land use map, map of the MV voltage domains, map of the MV/LV transformer stations power, etc.). A three-dimensional virtual city has been developed to visualize the graphical and attribute data for the study area. A Web and 3D Web GIS applications that allows the publication of the interactive maps on the Web as well as the database information have been developed to offer users the possibility of consulting the produced products by internet. Finally, a website related to the study was developed.

A pilot study on laser 3D printing of inorganic free-form micro-optics is experimentally validated. Ultrafast laser nanolithography is employed for structuring hybrid organic-inorganic material SZ2080TM followed by high-temperature calcination post-processing. The combination allows production of 3D architectures and the heat-treatment results in converting the material to inorganic substance. The produced miniature optical elements are characterized and their optical performance demonstrated. Finally, the concept is validated for manufacturing compound optical components such as stacked lenses. This is opening for new directions and applications of laser made microoptics under harsh conditions such as high intensity radiation, temperature, acidic environment, pressure variations, which include open space, astrophotonics, and remote sensing.

A detailed review of the scientific literature was undertaken to examine the most recent developments in plasma processing in the field of medicine. The first part of the review includes a detailed breakdown of the different types of coatings that can be applied onto medical devices using plasma, with a specific focus on antimicrobial surfaces. The developments during 2023 in plasma deposited biocompatible, drug delivery and adhesive coatings are described and specific applications in additive manufacturing are highlighted. The use of plasma and plasma activated liquids as standalone therapeutics continues to evolve and pertinent advances in this field are described. In addition, the combination of plasma medicine with conventional pharmaceutical interventions was reviewed and key emerging trends were highlighted, including the use of plasma to enhance drug delivery directly into tissue. The potential synergies between plasma medicine and chemotherapeutics for oncology and infection treatment is a growing area and recent advancements are noted. Finally, the use of plasma to control excess antibiotics and to intentionally degrade such materials in waste streams is described.

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.

Characters are one of the most important elements in composing digital animation. The appear-ance and voice of a character should be designed to express the personality and values of the character. However, it is not easy for animation producers to harmoniously match the appear-ance and voice of a character. Advances in deep learning technology have made it possible to overcome this limitation. To achieve this, firstly, an audio-visual dataset of characters is required. In this study, we construct and verify a Korean audio-visual dataset consisting of frontal face im-ages of various characters and short voice clips. We developed an application that can automati-cally extract the frontal face image and a short voice clip of a character by collecting videos up-loaded to YouTube. Through this, a dataset consisting of a total of 1,522 face images and a total of 7,999 seconds of voice clips was built based on 490 characters. Furthermore, we automatically la-bel characters by gender and age to validate the dataset. The dataset built in this study is expected to be used in various deep learning fields, such as classification, generative adversarial networks, and speech synthesis.

The 3D reconstruction of vermiculite-based sealing material was carried out based on CT scanning experiments and Avizo software. The precision and representation of the reconstructed digital core were tested by calculating the pore structure parameters and comparing them with the experimental results of mercury compression. Avizo is a perfect interface with Fluent software to perform micro-scale seepage simulation to explore the distribution of pressure and velocity fields during fluid transport. In this paper, a new approach is proposed to study the penetration leakage of non-metallic gaskets by using equivalent pore networks.

The three-dimensional Ising model on the m$\times$n$\times$l cubic lattice with the screw boundary condition along the ${\bf X}$ direction and the periodic boundary conditions along both ${\bf Y}$ and ${\bf Z}$ directions is exactly solved by using the $2^{mn}$-dimensional representation of the rotation group in $2mn$-dimensions, similar to the Kaufman's spinor approach in two dimensions. The exact partition function is obtained from two sets of $2^{mn-1}$ eigenvalues of the $2^{mn}$-dimensional transfer matrix {\bf V} corresponding to the even and odd eigenvectors, respectively. Such the eigenvalues are determined by the angles of the 2mn-dimensional rotation associated with {\bf V}.

In this article, metallic additive manufacturing (AM) processes were classified and demonstrated. AM technology can be applied to a wide range of industrial areas because of its great feasibility in the design and manufacturing of various complex parts. The main factor that distinguishes various metallic AM processes from each other is the deposition method. Deposited metal can be imported in the form of melt or semi-solid. AM technology also covers a wide range of materials like aluminum, titanium, and many other alloys. Some of the common applications of metallic AM processes are the quick manufacturing of the parts which utilized in various industries like medical, automotive, aerospace, and jewelry industries. AM can help to fabricate parts that are impossible to be manufactured by other processes.

Existing methods for 3D human pose estimation mainly divide the task into two stages. The first stage identifies the 2D coordinates of the human joints in the input image, namely the 2D human joint coordinates. The second stage uses the results from the first stage as input to recover the depth information of human joints from the 2D human joint coordinates to achieve 3D human pose estimation. However, the recognition accuracy of the two-stage method relies heavily on the results of the first stage and includes too many redundant processing steps, which reduces the inference efficiency of the network. To address these issues, we propose the EDD, a fully End-to-end 3D human pose estimation method based on transformer architecture with Dual Decoders. By learning multiple human poses, the model can directly infer all 3D human poses in the image using a pose decoder, and then further optimize the recognition result using a joint decoder based on the kinematic relations between joints. With the attention mechanism, this method can adaptively focus on the most relevant features to the target joint, effectively overcoming the feature misalignment problem in the human pose estimation task and greatly improving the model performance. Any complex post-processing step, such as non-maximum suppression, is eliminated, further improving the efficiency of the model. The results show that the method achieves an accuracy of 87.4% on the MuPoTS-3D dataset, significantly improving the accuracy of end-to-end 3D human pose estimation methods.