This study extends the CGAN-based MODIS cloud vertical-profile (64×64-scene, about 70km width×15km height) retrieval technique developed by Leinonen et al. (2019) [1] to construct seamless 3D cloud fields for the MODIS granules [2]. Firstly, the accuracy and spatial continuity of the Leinonen et al. [1] retrievals are statistically evaluated. Then, according to the characteristics of the retrieval error, a spatially overlapping-scene ensemble generation method and a bi-directional Ensemble Binning Probability Fusion (CGAN-BEBPF) technique are developed, which improves the CGAN retrieval accuracy and support to construct seamless 3D clouds. The CGAN-BEBPF technique involves three steps: cloud masking, intensity scaling, and optimal value selection. It ensures adequate coverage of the low reflectivity areas while preserving the high reflectivity cloud cores. The technique is applied to retrieve the 3D cloud fields of Typhoon Chaba and a multi-cell convective system. The cloud structures of the CGAN-BEBPF results are highly consistent with the ground-based radar observations. It can retrieve weak clouds at the top levels of convective storms and hurricanes that were missed by ground-based radars and fill the gaps of the ground-based radar lower-level PPI scan. Overall, CGAN-BEBPF can be automated to retrieve the rich informative 3D structures of typhoons and severe convective systems over the oceans along the MODIS swath, which certainly presents great value for improving maritime and near-shore typhoons and convection prediction and other cloud-sensitive applications.

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

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.

Chimeric Antigen Receptor (CAR)-T cell immunotherapy revolutionized cancer treatment and consists of the genetic modification of T lymphocytes with a CAR gene, aiming to increase their ability to recognize and kill antigen-specific tumor cells. The dynamics of CAR-T cell responses in patients presents a multiphasic kinetics with distribution, expansion, contraction, and persistence phases. The characteristics and duration of each phase depend on the tumor type, the infused product, and on patient-specific characteristics. We present a mathematical model which describes the multiphasic CAR-T cell dynamics resulting from the interplay between CAR-T and tumor cells, considering patient and product heterogeneities. The CAR-T cell population is divided into functional (distributed and effector), memory, and exhausted CAR-T cell phenotypes. The model is able to describe the diversity of CAR-T cell dynamic behaviors in different patients and hematological cancers as well as their therapy outcomes. Our results indicate that the joint assessment of the area under the concentration-time curve in the first 28 days and the corresponding fraction of non-exhausted CAR-T cells may be considered as potential markers to classify therapy responses. Overall, the analysis of different CAR-T cell phenotypes can be a key aspect for a better understanding of the whole CAR-T cell dynamics.

Copulas are useful tools for modeling the dependence structure between two or more variables. Copulas are becoming a quite flexible tool in modeling dependence among the components of a multivariate vector, in particular to predict losses in insurance and finance. In this article, we study the dependence structure of some well-known real life insurance data (with two components mainly) and subsequently identify the best bivariate copula to model such a scenario via VineCopula package in R. Associated structural properties of these bivariate copulas are also discussed.

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.

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.

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.

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.

The solar heat pump system based on photovoltaic photothermal (PV/T) modules is a new technology that integrates photovoltaics and heat reutilization. It can improve the efficiency of photovoltaic conversion and recovery the remaining heat generated during the photoelectric conversion process, thereby improving the comprehensive efficiency of the whole system. Simulink software is a visual simulation tool, which has the advantages of strong applicability, clear simulation structure and calculation process. The design of its graphical programming greatly simplifies the user modeling process and allows for direct viewing of results, therefore improving the simulation efficiency. At present, there is little research on simulation of solar heat pump systems with PV/T modules based on Simulink software. In this paper, the mathematical models of each component contained in the PV/T solar heat pump system were established based on the system working principle, energy conservation equations and some empirical formulas, and then the operation of the system was simulated by the Simulink software. Due to the operation characteristic of PV/T modules is the key influencing factor for the whole system performance, the model and simulation process for PV/T modules were introduced in detail. The results showed that the surface temperature of PV/T modules under different operating conditions was significantly lower than that of ordinary photovoltaic panels, and the temperature change amplitude was lower. As results, the power generation and photovoltaic conversion efficiency were significantly improved.

Recent advances in sensor and platform technologies such as satellite systems, unmanned aerial vehicles (UAV), manned aerial platforms, and ground-based sensor networks have resulted in massive volumes of data is produced and collected about the earth. Processing, managing, and analyzing these data is one of the main challenges in 3D synthetic representation used in modeling and simulation (M&S) of the natural environment. M&S devices, such as flight simulators, traditionally require a variety of different databases to provide a synthetic representation of the world. M&S often requires integration of data from a variety of sources stored in different formats. Thus, for simulation of a complex synthetic environment, such as a 3D terrain model, tackling interoperability among its components (geospatial data, natural and man-made objects, dynamic and static models) is a critical challenge. Conventional approaches used local proprietary data models and formats. These approaches often lacked interoperability and created silos of content within the simulation community. Therefore, open geospatial standards are increasingly perceived as a means to promote interoperability and reusability for 3D M&S. In this paper, the Open Geospatial Consortium (OGC) CDB Standard is introduced. “CDB” originally refers to Common DataBase which is currently considered as a name with no abbreviation in the OGC community. The OGC CDB is an international standard for structuring, modeling, and storing geospatial information required in high performance modeling and simulation applications. CDB defines the core conceptual models, use cases, requirements, and specifications for employing geospatial data in 3D M&S. The main features of the OGC CDB Standard are described as run-time performance, full plug-and-play interoperable geospatial data store, usefulness in 3D and dynamic simulation environment, ability to integrate proprietary and open-source data formats. Furthermore, compatibility with the OGC standards baseline reduces the complexity of discovering, transforming, and streaming geospatial data into the synthetic environment and makes them more widely acceptable to major geospatial data/software producers. This paper includes an overview of OGC CDB version 1.0 which defines a conceptual model and file structure for the storage, access, and modification of a multi-resolution 3D synthetic environment data store. Finally, this paper presents a perspective of future versions of the OGC CDB and what the steps are for humanizing the OGC CDB standard with the other OGC/ISO standards baseline.

Targeted radionuclide therapy (TRT) has recently seen a surge in popularity, with the use of radionuclides conjugated to small molecules and antibodies. Similarly, immunotherapy also has shown promising results – an example being chimeric antigen receptor (CAR) T-cells therapy in hematologic malignancies. Moreover, TRT and CAR T therapies possess unique features that require special consideration when determining how to dose, time, and sequence combination treatments, including the distribution of TRT dose in the body, the decay rate of the radionuclide, and the proliferation and persistence of the CAR-T cells. These characteristics complicate additive or synergistic effects of combination therapies and warrant a mathematical treatment which includes these dynamics in relation to the proliferation and clearance rates of the target tumor cells. Here we combine two previously published mathematical models in a multiple myeloma setting to explore the effects of dose, timing, and sequencing of TRT and CAR-T cell based therapies. We find that for a fixed TRT and CAR-T cell dose, the tumor proliferation rate is the most important parameter in determining the best timing of TRT and CAR T therapies.

Accurate forecasts of ocean waves energy can not only reduce costs for investment but it is also essential for management and operation of electrical power. This paper presents an innovative approach based on the Long Short Term Memory (LSTM) to predict the power generation of an economical wave energy converter named “Searaser”. The data for analyzing is provided by collecting the experimental data from another study and the exerted data from numerical simulation of searaser. The simulation is done with Flow-3D software which has high capability in analyzing the fluid solid interactions. The lack of relation between wind speed and output power in previous studies needs to be investigated in this field. Therefore, in this study the wind speed and output power are related with a LSTM method. Moreover, it can be inferred that the LSTM Network is able to predict power in terms of height more accurately and faster than the numerical solution in a field of predicting. The network output figures show a great agreement and the root mean square is 0.49 in the mean value related to the accuracy of LSTM method. Furthermore, the mathematical relation between the generated power and wave height was introduced by curve fitting of the power function to the result of LSTM method.

The kinetics and modeling of dual-wavelength controlled photopolymerization confinement (PC) are presented and measured data are analyzed by analytic formulas and numerical data. The UV-light initiated inhibition effect is strongly monomer-dependent and different monomers have different C=C bond rate constants and conversion efficacy. Without the UV-light, for a given blue-light intensity, higher initiator concentration (C₁₀) and rate constant (k’) lead to higher conversion, as also predicted by analytic formulas, in which the total conversion rate (R_T) is an increasing function of k’R, which is proportional to k[gB₁C₁]^0.5. However, the coupling factor b₁ plays a different role that higher b₁ leads to higher conversion only in the transient regime; whereas higher b₁ leads lower steady-state conversion. For a fixed initiator concentration C₁₀, higher inhibitor concentration (C₂₀) leads to lower conversion due to stronger inhibition effect. However, same conversion reduction was found for the same H-factor of H₀ = [b₁C₁₀ - b₂C₂₀]. Conversion of blue-only are much higher than that of UV-only and UV-blue combined, in which high C₂₀ results a strong reduction of blue-only-conversion, such that the UV-light serves as the turn-off (trigger) mechanism for the purpose of spatial confirmation within the overlap area of UV and blue light. For example, UV-light controlled methacrylate conversion of a glycidyl dimethacrylate resin formulated with a tertiary amine co-initiator, and butyl nitrite, subject to a continuous exposure of a blue light, but an on-off exposure of a UV-light. Finally, we developed a theoretical new finding for the criterion of a good material/candidate governed by a double ratio of light-intensity and concentration, [I₂₀C₂₀.]/[I₁₀C₁₀].

The possibility of using additive manufacturing (AM) in the medicine area has created a new opportunities in health care. This has contributed to a sharp increase in demand for 3D printers, their systems and materials that are adapted to strict medical requirements. We described herein a medical-grade thermoplastic polyurethane (S-TPU), which was developed and then formed into a filament for Fused Deposition Modeling (FDM) 3D printers during a melt-extrusion process. S-TPU consisting of aliphatic hexamethylene 1,6-diisocyanate (HDI), amorphous α,ω-dihydroxy(ethylene-butylene adipate) (PEBA) and 1,4 butandiol (BDO) as a chain extender, was synthesized without the use of a catalyst. The filament properties were characterized by rheological, mechanical, physico-chemical and in vitro biological properties. The tests showed biocompatibility of the obtained filament as well as revealed no significant effect of the filament formation process on its properties. This study may contribute to expanding the range of medical-grade flexible filaments for standard low-budget FDM printers.

Along time, many minted coins were withdrawn from circulation, being replaced with new ones. The returned obsolete metal coins were melted in order to sustainable reuse of the alloy for other purpose. Between the withdrawing and melting, some of the metal coins were cancelled by destruction of the original shape and dimension, using some adequate tools. In the first part, the paper is focused to present some aspects insight of the cancelling method used on the Romanian old nickel coins; also, there are presented some examples. The introductive part also includes the literature review in the field of coin manufacturing, covering the subjects as metal behavior under the striking load, aspects about the 3D modeling and FEM analysis or explaining some striking errors. Result the paper main purpose, to study the particularities of one or another cancelling method applied on subjected coins, which conducted to more or less valuable collection metal pieces. In the paper second part, is introduced the adequate 3D model, computed for the cancelling dies, respectively the coin. Then, there are introduced the assembled models, corresponding to each cancelling case, which consist by the obverse and reverse cancelling dies, having the coin inside them. For the each model, the finite element analysis is realized and is achieved for different initial conditions. The final part of the paper presents the analysis results and also the discussions and conclusions.

We propose a non-invasive approach to control the quality of spheroids and their fusion into a complex bioconstruct. The proposed method is based on the union of the nutrient concentration change calculated using Fick's law and the "reaction-diffusion" equations, taking into account absorption coefficient with specifying the exact fusion geometry using implicit Function Repre-sentation (FRep) functions. The proposed approach allows us to analyze the viability of cells within the spheroid, predict the fusion of spheroids, and accurately model complex heteroge-neous biostructures as a future task for our research. These results will significantly accelerate the development of such a promising field of additive biotechnologies as 3D bioprinting.

Detailed kinetics for a 3-wavelength photopolymerization confinement (PC) system is presented for both numerical solutions and analytic formulas. The dynamic profiles are simulated for oxygen, free radical, and conversion for various situations of: blue-light only, 2-light (red and UV), and 3-light (red, blue, UV). An effective PC requires two conditions: (i) a strong N-inhibition for uncured regime with a low conversion (triggered by the UV-light); and (ii) a weak S-inhibition (oxygen-induced) for high conversion under the blue-light or blue and red-light initiation. Good PC candidates are governed by collective factors of: (i) the double ratio of light-intensity and initiator-concentration, (ii) monomers rate-constant; and (iii) effective absorption constants at specific wavelength and initiators. A new reverse feature for the role of N-inhibition on the blue-conversion is found. Higher oxygen concentration leads to a lower conversion, which could be enhanced by reducing the S-inhibition via a red or blue-light pre-irradiation, having a pre-irradiation time TP=200 s for red-light only, and reduced to 150 s, when both red and blue-light. System under UV-only leads a conversion lower than that of blue-only. However, conversion could be improved by the dual-light (blue and UV), and further enhanced by the pre-irradiation of red-light. The two competing factors, N-inhibition and S-inhibition, could be independently and selectively tailored to achieve: (a) high conversion of blue-light (without UV-light), enhanced by red-light pre-irradiation for minimal S-inhibition; and (b) efficient PC initiated by UV-light produced N-inhibition for reduced confinement thickness and for high print speed.

Selective laser melting (SLM) is one of the widely used techniques in metallic additive manufacturing, in which high-density laser powder is utilized to selectively melting layers of powders to create geometrically complex parts. Temperature distribution and molten pool geometry directly determine the balling effect, and concentrated balling phenomenon significantly deteriorates surface integrity and mechanical properties of the part. Finite element models have been developed to predict temperature distribution and molten pool geometry, but they were computationally expensive. In this paper, the three-dimensional temperature distributions are predicted by analytical models using point moving heat source and semi-ellipsoidal moving source respectively. The molten pool dimensions under various process conditions are obtained from the three-dimensional temperature predictions and experimentally validated. Ti-6Al-4V alloy is chosen for the investigation. Good agreements between the predictions and the measurements are observed. The presented models are also suitable for other metallic materials in the SLM process.

Accurate geometric modeling of blood vessels lumen given their 3D images is a basis for vessel quantification in support of cardiovascular diseases diagnosis, treatment and monitoring. Unlike other approaches, which assume circular or elliptical vessel cross-section, the proposed method employs parametric B-splines combined with the image formation system equations to accurately localize the highly curved lumen boundaries. No image segmentation is involved which might reduce the localization accuracy in effect of spatial discretization. It is shown that the model parameters can be reliably identified by a feedforward neural network which, driven by the cross-section images, predicts the parameter values many times faster than a reference least-squares (LS) model fitting algorithm. Two example applications: modeling the lower extremities artery-vein complexes visualized in steady-state contrast-enhanced magnetic resonance images (MRI) and the coronary arteries pictured in computed tomography angiograms (CTA), are presented and discussed to demonstrate the method potential. Besides application to medical diagnosis, blood-flow simulation and vessel-phantom design, it can serve as a tool for automated annotation of image datasets required to train machine-learning algorithms.

Drone imagery has the potential to enrich urban planning and preservation, especially where it converges with the growing creation and use of 3D models. The authors have conducted a systematic literature review of articles published between 2002 and 2022, drawing from reputable academic repositories including Science Direct, Web of Science, and China National Knowledge Infrastructure (CNKI), to identify current gaps in existing research in the application of UAVs to the creation of 3D models in urban planning and preservation. Findings indicate five research shortcomings: limited participation of planning experts, research focus imbalance, lack of usage for special scenarios, lack of integration with smart city planning, and limited interdisciplinary collaboration. The study also acknowledges current limitations with UAV applications and discusses possible countermeasures as well as future prospects.

The paper formulates requirements for a polymer material for molding products from it by fused deposition modeling. A methodology for evaluating the suitability of a polymer or composite of thereof in 3D printing technology has been developed. A graphic representation of the developed methodology in the form of a temperature-shear rate logarithm diagram is proposed. Application of the proposed methodology makes it possible to simplify the development of new materials for 3D printing by fused deposition modeling both at the stage of selecting the components of the polymer composition and at the stage of its subsequent approbation.

Among many other themes, Leonardo da Vinci’s Manuscript B contains several drawings of centrally planned churches, some of which are represented using a plan view paired with a bird’s-eye view. The use of a bird’s-eye instead of an elevation represents an innovative depiction technique, which allows to combine the immediacy of the perspective view with the measurability of the façades, and therefore to describe the three-dimensionality of the buildings. To understand the reasons behind the use of this original technique, the edifices’ shape and classify them we decided to use 3D digital reconstruction techniques, for their ability to avoid misunderstandings in the reconstruction process and in the results. This article describes the method to create the digital models of sixteen churches. A Visual programming language (VPL) script was used as 3D base for modelling the churches achieved from a classification code expressing the aggregative rules of the churches. Then, the geometric process for the construction of the plan and its relationship with the elevation measures was studied for each church. Finally, this information was used for the completion of the 3D models, distinguishing more output variants each time there was an inconsistency between plan and perspective view, a variability of one architectural element or an uncertainty.

Adaptive T cell immunotherapy holds great promise for the successful treatment of leukemia as well as other types of cancers. More recently, it was also shown to be an effective treatment option for chronic virus infections in immunosuppressed patients. Autologous or allogeneic T cells used for immunotherapy are usually genetically modified to express novel T cell or chimeric antigen receptors. The production of such cells was significantly simplified with the CRISPR/Cas system allowing deletion or insertion of novel genes at specific locations within the genome. In this review, we describe recent methodological breakthroughs important for the conduction of these genetic modifications, summarize crucial points to be considered when conducting such experiments, and highlight the potential pitfalls of these approaches.

Currently, multiple studies have indicated that CD8+ T lymphocytes play a role in causing damage to the exocrine glands through acinar injury in Primary Sjogren’s syndrome (pSS). The aim of this research was to assess the imbalance of subsets within CD8+ cells in peripheral blood. We examined blood samples from 34 patients with pSS and 34 healthy individuals as controls. We used flow cytometry to enumerate CD8+ T cell maturation stages using as markers CD62L, CD28, CD27, CD4, CD8, CD3, CD45RA, and CD45. For immunophenotyping of ‘polarized’ CD8+ T cell subsets we used the following monoclonal antibodies:CXCR5, CCR6,CXCR3 and CCR4. The findings revealed that both the relative and absolute numbers of 'naïve' CD8+ T cells were higher in pSS patients compared to the healthy volunteers. Conversely, the proportions of effector memory CD8+ T cells were notably lower. Furthermore, our data suggested that among patients with pSS, the levels of cytotoxic Tc1 CD8+ T cells were reduced, while the frequencies of regulatory cytokine-producing Tc2 and Tc17 CD8+ T cells were significantly elevated. Simultaneously, the Tc1 cell subsets displayed a negative correlation with immunoglobulin G, Rheumatoid factor, the Schirmer test, and unstimulated saliva flow. On the other hand, the Tc2 cell subsets exhibited a positive correlation with these parameters. In summary, our study indicated that immune dysfunction within CD8+ T cells, including alterations in Tc1 cells, plays a significant role in the development of pSS.

Researchers have developed and used several three-dimensional (3D) culture systems, including spheroids, organoids, and tumoroids. Drug resistance is a crucial issue involving recurrence in cancer patients. Many studies on anticancer drugs have been done in 2D culture systems, where-as 3D cultured tumoroids have many advantages for assessing drug sensitivity and resistance. Here, we aim to investigate whether Cisplatin (a DNA crosslinker), Imatinib (a multiple tyro-sine kinase inhibitor), and 5-Fluorouracil (5-FU: an antimetabolite) alter tumoroid growth of metastatic colorectal cancer (mCRC). To establish a liquid-based 3D multiplexing reporter assay system, LuM1 (a murine mCRC cell line) was stably transfected with the Mmp9 promoter-driven ZsGreen reporter gene, which was designated as LuM1/m9 cells and cultured in NanoCulture Plate (NCP), a 3D culture device. The larger tumoroids were not sensitive to Cisplatin and ex-pressed ABCG2 (a marker of cancer stem cells, a.k.a. a drug efflux transporter), whereas smaller cell-aggregates were more sensitive to Cisplatin. Both Imatinib and Cisplatin significantly in-creased tumoroid growth (larger than 300 μm2) and Mmp9 promoter activity and were not cytotoxic to the mCRC tumoroids. On the other hand, 5-FU was cytotoxic to the tumoroids and significantly inhibited tumoroid growth, although not completely. Thus, platinum resistance and imatinib resistance in mCRC were modeled using the liquid-based 3D cultured tumoroid system. The tumoroid culture is useful and easily accessible for the assessment of drug sensitivity and resistance.

Immune surveillance and adaptive immune responses, involving continuously circulating and tissue-resident T-lymphocytes, provide host defense against infectious agents and possible malignant transformation while avoiding autoimmune tissue damage. Activation, migration, and deployment of T-cells to affected tissue sites are crucial for mounting an adaptive immune response. An effective adaptive immune defense depends on the ability of T-cells to dynamically reprogram their metabolic requirements in response to environmental cues. Inability of the T-cells to adapt to specific metabolic demands may skew cells to become either hyporesponsive creating immunocompromised conditions or hyperactive causing autoimmune tissue destruction. Here, we review maladaptive T-cell metabolic fitness that can cause autoimmune diseases and discuss how T-cell metabolic programs can potentially be modulated to achieve therapeutic benefits.

This article presents, for the first time, the efficacy and curing depth analysis of photo-thermal dual polymerization in metal (Fe) polymer composites for 3D printing of a 3-component (A/B/M) system based on the proposed mechanism of our group, in which the co initiators A and B are Irgacure-369, and charge-transfer complexes (CTC), respectively; and the monomer M is filled by Fe. Our formulas show the depth of curing (Zc) is an increasing function of the light intensity, but a decreasing function of the Fe and photoinitiator concentrations. Zc is enhanced by the additive [B] which produces extra thermal radical for polymerization under high temperature. The heat (or temperature) increase in the system has two components : (i) due to the light absorption of Fe filler, and (ii) heat released from the exothermic photopolymerization of the monomer. The heat is transported to the additive (or co-initiator) [B] to produce extra radical R' and enhance the monomer conversion function (CF). The Fe filler leads to temperature increase, but also limits the light penetration leading to lower CF and Zc, which could be overcome by the additive initiator [B] in thick polymers. Optimal Fe for maximal CF and Zc are explored theoretically.

This article presents, for the first time, the kinetics and the general conversion features of a 3-component system, BT(BC)/iodonium/Amine, based on proposed mechanism of Liu et al, for both free radical polymerization (FRP) of acrylates and the free radical promoted cationic polymerization (CP) of epoxides using the new multi-functional initiator of benzophenone–triphenylamine (BT). The additives, iodonium and EDB, have the dual function of (i) regeneration BT and (ii) produce of extra radicals for improved FRP and CP. Analytic formulas are developed to explore the new features including: (i) the conversion efficacy (CE) of FRP is an increasing function of the light intensity, the effective absorption coefficient, and the concentration sum of each of the components, BT, Iod, amine, for transient state. However, CE at steady-state is independent to the light intensity; (ii) the trifunctional hybrid structures of BT3 leads to larger light absorption than other types of BT; it also provides more active sites for the H-abstraction in the presence of EDB, leading to high CE; (iii) the efficacy of FRP is an increasing function of the amine (EDB) concentration, in contrast to that of CP having an opposite dependence; (iv) the consumption rate of BT3 in the BT3/ Iod/EDB system is slower than that of the BT3/Iod system due to photoredox catalytic cycle, and the larger initiator regeneration (RGE)
in the three-component system. A comprehensive model is also proposed that the CE (for both FRP and CP) is governed by (N_jK_jbI), whereas more complex formulas are developed; where Kj is an effective rate constant proportional to the electron transfer quantum yield, and the combined effects of other coupling rate constants; b is an effective absorption coefficient given by the light absorption and excited state quantum yield.

Naive CD4+ T cells engage cognate peptide MHC-II complexes (pMHC-IIs) to differentiate and acquire one of several T helper (Th) fates whose specific trajectories are guided by a dynamic cytokine milieu that develops in response to antigenic entity. This physiological process is often erroneously conflated with a pathological one termed Th polarization. Using the SPIRAL model, we argue here that unlike Th fate choice, innate signaling alone is insufficient to initiate Th polarization in naive CD4+ T cells, that it instead develops from pre-existing memory CD4+ T cells that express cross-reactive TCRs, and that it inevitably leads to immunopathology.

Based on the historical research on the shape of armor in Ming Dynasty, this paper explores the shape characteristics of general armor in Ming Dynasty in China through field research on the general stone statue of Ming Xiaoling Mausoleum in Nanjing. Through Ming Xiaoling Mausoleum general stone carving 3D animation technology restoration project, virtual material heritage practice is carried out. Through the modeling of the general stone statue in Ming Xiaoling Mausoleum by MAYA and Zbrush, UE4 realizes the construction of scenes and the output of interactive effects, so as to explore a mode of application engine animation that can preserve and propagate general stone carving in Ming Xiaoling Mausoleum.

Cancer metastasis into the brain constitutes one of the most severe but not uncommon development of cancer growth. Several factors control how cancer types interact with the brain to establish metastasis These factors include system of migration, system of infiltration of the blood-brain barrier and the interaction with host cells (e.g., neurons, astrocytes) and the immune system fight against metastasis in the brain. Although, brain radiotherapy is the main treatment procedure carried out to treat, new therapies are emerging that constitute a glimpse of hope for increasing the diminutive life expectancy currently forecasted to cancer patients who are facing the prospectus of brain metastasis. However applying these therapeutic strategies has been has not been effective. Thus there is a need for better understanding of the metastasis process in order to suggest novel therapeutic targets. In this review, we follow the journey of various cancer cells from their primary location through the various process that they undergo including EMT, penetration of the ECM, intravasation, extravasation and infiltration of the blood brain barrier ending up with colonization and angiogenesis. In each phase, we focus on molecules that could potentially be drug target candidates.

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.

Despite exhaustive studies, researchers have made little progress in the field of adoptive cellular therapies for relapsed-refractory acute myeloid leukemia (AML), unlike the notable uptake for B cell malignancies. Various single antigen targeting chimeric antigen receptor (CAR) T cell Phase I trials have been established worldwide and have recruited approximately 100 patients. The high heterogeneity at the genetic and molecular levels within and between AML patients resembles a black hole: a great gravitational field that sucks in everything, considering only around 30% of patients show a response but with consequential off-tumor effects. It is obvious that a new point of view is needed to achieve more promising results. This review first introduces the unique therapeutic challenges of not only CAR T cells but also other adoptive cellular therapies in AML. Next, recent single cell sequencing data for AML to assess somatically acquired alterations at the DNA, epigenetic, RNA and protein levels are discussed to give a perspective on cellular heterogeneity, intercellular hierarchies, and the cellular ecosystem. Finally, promising novel strategies are summarized, including more sophisticated next-generation CAR T, TCR-T and CAR-NK therapies; approaches to tailor the microenvironment and target neoantigens; and allogeneic approaches.

CAR-T therapy has achieved considerable treatment success in hematologic tumors by using patient derived autologous αβ T cells. There is an impetus to broaden the applicability of this approach by using a third-party donor derived CAR-T cell product which has a potent anti-tumor function but a constrained GVHD property. In this study, CAR-T cells were prepared from Vγ9Vδ2 T cells expanded by using a novel prodrug PTA and their anti-tumor functions were assessed in conjunction with persistency, localization, and phenotype. γδ T cells were successfully transduced with a CAR specific to CEA with signaling domains of CD3ζ and CD28 (CEA.CAR-γδ T cells), and exhibited potent tumor killing function in vitro. In a xenograft mouse model, CEA.CAR-γδ T cells suppressed CEA+ tumor growth though a limited time window. CEA.CAR-γδ T cells persisted and accumulated in the tumor even after tumor progression, however, ex vivo analysis revealed that those recovered at different time points from PBMC, spleen and tumors gradually lost tumor reactivity as assessed by IFN-γ production. Provision of GITR co-stimulation enhanced anti-tumor function of CEA.CAR-γδ T cells, the result of which imposes additional measurers to be adopted in CAR-γδ T cells for an allogeneic adoptive immunotherapy.

Long non-coding RNA (lncRNA) aberrant expression have been found in several types of cancer, including acute lymphoblastic leukemia (ALL), but lncRNA mapped in transcribed ultraconserved regions (T-UCRs) are little explored. The T-UCRs uc.112, uc.122, uc.160 and uc.262 were evaluated in pediatric ALL and uc.112 expression was higher in T-ALL compared to patients with B-ALL and in patients with hyperdiploid karyotype. These findings suggest a potential role of this uc.112 in pediatric ALL and emphasize the need for further investigation of T-UCR in pediatric ALL.

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.

The increase in incidence of superficial fungal infections combined with the emergence of antifungal resistance represents both a global health challenge and a considerable economic burden. Recently, dermatophytes, the main culprit causing superficial fungal infections, have started to exhibit antifungal resistance. This can be observed in some of the most common species such as Trichophyton rubrum and Trichophyton mentagrophytes. Importantly, the new subspecies, known as Trichophyton indotineae, has been reported to show high resistance to terbinafine, a first-line treatment for dermatophyte infections. Compounding these issues is the realization that diagnosing the causative infectious agents requires using molecular analysis that goes beyond the conventional macroscopic and microscopic methods. These findings emphasize the importance of conducting antifungal susceptibility testing to select the appropriate antifungal necessary for successful treatment. Implementing these changes may improve clinical practices that combat resistant dermatophyte infections.

Transfer factor is the name given to material derived from activated lymphocytes that is probably composed of a complex of a peptide and a short segment of RNA and which has the reported ability to transfer specific T cell immunity to uncommitted lymphocytes. Many independent groups around the world reported isolating transfer factors between 1955 and 1990 and demonstrating their ability to transfer passive immunity from one animal or individual to another, often within 24 hours of inoculation. Such activity is potentially revolutionary both in making T cell vaccines readily manufacturable and also because the existence of transfer factors would undermine the basic assumptions of the clonal selection theory, which currently dominates immunological theory. Unfortunately, lack of the microanalytical and synthetic techniques required to properly identify transfer factors, combined with safety factors associated with it derivation from blood sources susceptible to HIV and prion infections, put an end to transfer factor research after 1990. This paper reviews the evidence supporting transfer factor activity and suggests that this potentially revolutionary concept be resurrected and subjected to renewed scrutiny in light of CRISPR-Cas mechanisms and because of its potential to make possible T cell vaccination and provide a novel basis for understanding immunological function.

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.

In recent years, new treatments have been studied for relapsed-refractory multiple myeloma (RRMM), including two CAR-T products and a variety of non CAR-T agents. Since direct comparisons between these innovative treatments are not available, indirect comparisons can be of interest. Reconstruction of individual patient data from Kaplan-Meier graphs (Shiny method) has been employed in numerous reports that have validated its performance. In the present review, we evaluated six treatments proposed for RRMM including two CAR-T products (ciltacabtagene autoleucel and idecabtagene vicleucel) and four treatments not based on a CAR-T (melflufen plus dexamethasone, isatuximab plus dexamethasone, selinexor, and belantamab). The end-point was overall survival (OS); the Shiny method was used to generate reconstructed survival curves. Our results showed statistically significant differences in OS across these treatments. Compared with pharmacological treatments, CAR-T products significantly prolonged OS with an improvement of remarkable clinical relevance. In particular, ciltacabtagene autoleucel showed better OS than idecabtagene vicleucel. As regards non CAR-T treatments, the ranking in OS was headed by isatuximab plus dexamethasone, followed by belantamab, selinexor, and melflufen plus dexamethasone. In conclusion, while the Shiny method has confirmed its validity in reconstructing individual patient data, our indirect comparisons have offered some original clues to better interpret the information on OS published in these studies.

Hamacher operation which is generalization of the Algebraic and Einstein operation, can widely provide a large number of arithmetical operation with respect to uncertainty information, and Heronian mean can deal with correlations of the input arguments or different criteria and don’t make calculation redundancy, meanwhile, the normal intuitionistic fuzzy numbers (NIFNs) can depict distinctively normal distribution information in practical decision making. In this paper, a multi-criteria group decision-making (MCGDM) problem is researched under the NIFNs environment, and a new MCGDM approach is introduced on the basis of the Hamacher operation. Firstly, according to Hamacher t-conorm and t-norm, some operational laws of NIFNs are presented. Secondly, it is noticed that Heronian mean can’t only once take into account mutual relation between attribute values once, but also consider the correlation between input argument and itself. Therefore, we develop some operators and study their properties in order to aggregate normal intuitionistic fuzzy numbers information, these operators include Hamacher Heronian mean (NIFHHM), Hamacher weighted Heronian mean (NIFHWHM), Hamacher geometric Heronian mean (NIFHGHM) and Hamacher weighted geometric Heronian mean (NIFHWGHM). Furthermore, we apply the proposed operators to the MCGDM problem and present a new method. The main characteristics of this new method involve that: (1) it is suitable to make decision under the normal intuitionistic fuzzy numbers environment and more reliable and reasonable to aggregate the normal distribution information. (2) it utilizes Hamacher operation which can provide more reliable and flexible decision-making results and offer an effective and powerful mathematic tool for the MAGDM under uncertainty. (3) it uses the Heronian mean operator which can considers relationships between the input arguments or the attributes and don’t brings subsequently about redundancy. Lastly, an application is given for showing the feasibility and effectiveness of the presented method in this paper.

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

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.

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.

Background: The effectiveness of the anti-COVID-19 vaccine remains a matter to be clarified. Methods: The humoral and cellular immunity after the administration of three doses of the Pfizer–BioNTech and Oxford AstraZeneca vaccines against SARS-CoV-2 over one year and the appearance of post-vaccination COVID-19 have been studied. Results: Anti-SARS-CoV-2 IgG and IgA antibodies showed a progressive increase throughout the vaccination period. This increase was greatest after the third dose. The highest levels were observed in subjects who had anti-SARS-CoV-2 antibodies prior to vaccination. There was an increase in CD4+ αβ, CD8+ γδ and TEM CD8+ γδ T cells, and a decrease in apoptosis in CD4+CD8+ and CD56+ αβ and γδ T cells. Post-vaccination SARS-CoV-2 infection was greater than 60%. The symptoms of COVID-19 were very mild and were related to γδ T cell deficit, specifically CD8+ TEMRA and CD56+ γδ TEM, as well as lower pre-vaccine apoptosis levels. Conclusions: Those results demonstrate the important role that γδ T cells play in SARS-CoV-2 vaccine immunization.

Therapeutic vaccine studies should be designed to elicit durable, high magnitude, and efficacious T cell responses, all of which can be impacted by the choice of vaccination schedule. Here, we compare different prime-boost intervals (PBI) in a human papillomavirus (HPV) model using HPV16E6E7 Venezuelan equine encephalitis virus replicon particle (VRP) vaccination to address the optimal boosting schedule, quality of immune response, and overall in vivo efficacy. Six different vaccine regimens were tested with each group receiving booster vaccinations at different time intervals. Analysis of T-cell responses demonstrated a significant HPV16 E7 specific CD8+T cell response with minimally a one-week PBI between antigen re-exposure. Significant E7-specific in vivo cytotoxicity was also observed with longer PBIs. Additionally, longer PBIs led to an enhanced memory recall response to tumor challenge, which correlated with differential expansion of T cell memory subsets. Our findings imply that when using alphavirus vector platforms as a vaccination strategy, a one-week PBI is sufficient to induce high magnitude effector T cells with potent anti-tumor activity. However, longer PBIs lead to enhanced long-term protective anti-tumor immunity. These findings have implications for therapeutic vaccine clinical trials in which shorter intervals of prime-boost regimens may lead to suboptimal durable immune responses.

Trichinella spp. are etiological zoonotic agents spread throughout the world affecting mammals, birds, and rep-tiles, involved in the evolution of the two cycles, domestic and sylvatic. The pine marten (Martes martes) is a mammal carnivorous nocturnal from the family Mustelidae. In Romania, this host is widespread in all the forests of the country. The pine marten has an extremely voracious appetite, feeding on fruit but also on a variety of small animals, including rodents such as mice or rats. The aim of the study was identification and molecular characterization of Trichinella larvae isolated from the muscles of tree martens from different counties of Romania. The muscle samples were examined by artificial digestion, and the larvae were processed by multiplex PCR. Trichinella britovi, a species frequently identified in wild carnivores in temperate zones, has been confirmed. Although T. britovi has been reported in Romania to several host animals, this study confirms for the first time its presence in the pine marten, a result which undoubtedly underlines the fact that the parasitic reserve in the sylvatic environment is maintained at a consistent level, and the knowledge of these vector hosts remains a permanent concern of the specialists.

Cryptococcal meningitis remains a significant opportunistic infection among HIV-infected patients, contributing 15%-20% of HIV-related mortality. A complication of initiating Antiretroviral therapy (ART) following opportunistic infection is Immune Reconstitution Inflammatory Syndrome (IRIS). IRIS afflicts 10-30% of HIV-infected patients with cryptococcal meningitis (CM), but its immunopathogenesis is poorly understood. We compared circulating T cell memory subsets and cytokine responses among 17 HIV-infected Ugandans with CM: 11 with and 6 without CM-IRIS. At meningitis diagnosis, stimulation with cryptococcal capsule component, glucuronoxylomannan (GXM) elicited consistently lower frequencies of CD4⁺ and CD8⁺ T cell memory subsets expressing intracellular cytokines (IL-2, IFN-γ and IL-17) among subjects who subsequently developed CM-IRIS. After ART initiation, T cells evolved to show a decreased CD8⁺ central memory phenotype. At the onset of CM-IRIS, stimulation more frequently generated polyfunctional IL-2⁺/IL-17⁺ CD4⁺ T cells in patients with CM-IRIS. Moreover, CD8⁺ central and effector memory T cells from CM-IRIS subjects also demonstrated more robust IL-2 responses to antigenic stimulation vs. controls. Thus, ART during CM elicits distinct differences in T cell cytokine production in response to cryptococcal antigens both prior to and during the development of IRIS, suggesting an immunologic foundation for the development of this morbid complication of CM infection.

The aim of this 9th expository article is to conclude a study on domination in two fuzzy models, including t−norm fuzzy graphs and fuzzy graphs. All parts are twofold even if we don’t men- tion, directly. I.e., all results depicts some properties about fuzzy graph and t−norm fuzzy graph.

The complete regression of clear cell renal cell carcinoma (ccRCC) obtained pre-clinically with anti-carbonic anhydrase IX (CAIX) G36 chimeric antigen receptor (CAR) T cells in doses equivalent to 10e8 CAR T cells/ Kg renewed the potential of this target to treat ccRCC and other tumors in hypoxia. The immune checkpoint blockade (ICB) brought durable clinical responses in advanced ccRCC and other tumors. Here we tested CD8/4-1BB compared to CD28-based anti-CAIX CAR PBMCs cells-releasing anti-programmed cell death ligand-1 (PD-L1) IgG4 for human ccRCC treatment in vitro and in an orthotopic NSG mice model in vivo. Using a 10e7 CAR PBMCs cells/ Kg dose, anti-CAIX CD28 CAR T cells releasing anti-PD-L1 IgG highly decrease both tumor volume and weight in vivo, avoiding the occurrence of metastasis. This antitumoral superiority of CD28-based CAR PBMCs cells compared to 4-1BB occurred under ICB via PD-L1. Furthermore, T cell exhaustion status in peripheral CD4 T cells, additionally to CD8 was critical for CAR T cells efficiency. The lack of hepatotoxicity and nephrotoxicity upon administration of 10e7 CAR PMBCs cells/Kg dose is the basis for carrying out clinical trials using anti-CAIX CD28 CAR PBMCs cells releasing anti-PD-L1 antibodies or anti-CAIX 4-1BB CAR T cells, offering exciting new prospects for the treatment of refractory ccRCC and hypoxic tumors.

Euler sums are alternating (or level two) extension of multiple zeta values (MZVs). Kaneko and Tsumura initiated the study of multiple T-values (MTVs), another level two generalization, by restricting the summation indices in the definition of MZVs to a fixed parity pattern. In this paper, we shall study finite MTVs and their alternating versions which are level two and level four variations of finite MZVs, respectively. We conjecture that all finite MZVs are in the Q-span of finite MTVs which in turn apparently lie in the span of finite Euler sums, and the inclusions are both proper. We shall first provide some structural results for Euler sums of small weights, guided by the author's previous conjecture that the finite Euler sum space of weight w is isomorphic to a quotient Euler sum space of weight w. Then, by utilizing some well-known properties of the classical alternating MTVs, we shall derive a few important Q-linear relations among the finite alternating MTVs, including the reversal, linear shuffle and sum relations. We then compute the upper bound for the dimension of the Q-span of weight w finite (alternating) MTVs for w<9, both rigorously using the newly discovered relations and numerically aided by computers.

Background: Takayasu Arteritis (TAK) increases vascular stiffness and arterial resistance. Hypertension and atherosclerosis lead to similar changes. We investigated possible differences in cardiovascular remodeling between these diseases and whether the differences are correlated with immune cell expression. Methods: Patients with active TAK arteritis were compared with age- and sex-matched hypertensive and atherosclerotic patients. In a subpopulation of TAK patients, Treg/Th17 cells were measured before (T0) and after 18 months (T18) of infliximab treatment. Echocardiogram, supraaortic Doppler ultrasound, and lymphocytogram were performed in all patients. Histological and immunohistochemical evaluation of the vessel wall was performed to compare the in vivo results. Results: TAK patients have increased aortic valve dysfunction and diastolic dysfunction. These data have been associated with uric acid levels. A significant increase in aortic stiffness was also noted and associated with peripheral T lymphocyte levels. CD3+CD4+ cell infiltrates were detected in the vessel wall samples of these patients. They had a lower mean percentage of Tregs at T0 than controls, but levels increased significantly at T18. Opposite results were found in Th17 cells. Finally, TAK patients were found to have an increased risk of atherosclerotic cardiovascular disease (ASCVD). Conclusion: Our data suggest that different pathogenic mechanisms of vessel damage, including atherosclerosis, underlie TAK patients compared with control subjects. The increased risk of ASCVD in TAK patients correlates directly with the degree of inflammatory cell infiltration in the vessel wall. Infliximab restores the normal frequency of Tregs/Th17 in TAK patients and allows a possible reduction of steroids and immunosuppressants.

Recently, many authors have been interested to introduce fuzzy implications over t-norms and t-conorms. In this paper, we introduce (S,N) and residuum fuzzy implication for Dubois t-norm and Hamacher's t-norm. Also, new concepts so-called (T,N) and residual fuzzy co-implication in dual Heyting Algebra are investigated. Some examples as well as application are discussed as well.

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 study investigated the impact of seven-strain probiotic supplementation on the frequency of T helper 17 (Th17) cells, regulatory T (T-reg) cells, Treg/Th17 ratio, and their gene expression in individuals with severe traumatic brain injury (STBI). Probiotics can influence the gut microbiota, modulate the immune response, and prevent or alleviate certain immune diseases. However, it is necessary to clarify whether probiotics can effectively impact Th cells in STBI patient. Despite the great attention to improving the immune system in most diseases, there is currently no accurate mechanism for the use of probiotics in diseases with damage to the head injury, which can be a basis for the use of probiotics. The primary objective of this study is to address this research gap. The present study was a randomized, double-blind, placebo-controlled trial that enrolled 48 STBI patients. They were treated with probiotics or placebo: 4 capsule/day for 14 days. The pre- and post-study evaluation included examining the frequency of Treg, Th17 cells, as well as the expression of associated immunological parameters (Foxp3 and RORγt) and Treg/Th17 ratio in both groups. No significant differences were found between the two groups in terms of subject characteristics (P>0.05). GCS scores at 14 days were significantly higher in the probiotic compared to the placebo group. The probiotic group showed a significant decrease in Th17 cell and RORγt gene expression (P = 0.022 and P< 0.001, respectively), a notable increase in T-reg and FoxP3 gene expression (P= 0.025 and P< 0.001, respectively), and a higher Treg/Th17 ratio compared to the placebo group. Our study provides promising evidence of the beneficial effects of seven-strain probiotic supplementation on Th cells in individuals with STBI.

Background: Emerging data indicate that radiotherapy can modulate antitumour immune responses. Regulatory T cells (Tregs) are a key immunosuppressive subpopulation of interest. We aimed to evaluate the impact of conventional fractionated radiotherapy on circulating Treg levels in melanoma patients and to determine the correlation between these changes and survival. Understanding radiotherapy–immunity interactions may facilitate personalized combination therapies. Methods: Peripheral blood samples from 32 melanoma patients were analysed to quantify Tregs before and 1-3 months after regional lymph node radiotherapy using flow cytometry. Tregs were characterized as CD4+/CD25+/CD127-. Total CD4+ T cells were also evaluated. Changes were compared to those in a control group of 30 tumor-free patients. Overall survival was correlated with T-cell subset dynamics induced by radiotherapy. Results: At baseline, the median percentage of Tregs was not significantly lower in melanoma patients than in controls (7.4% vs 8.32%, p=0.17). Radiotherapy markedly increased the median Treg count to 10.01% (p=0.0008), with a concomitant increase in total CD4+ cells (to 11.71%, p=0.001), indicating systemic expansion. Patients exhibiting coordinated increases in Treg and CD4+ T cells after treatment had a significantly improved prognosis compared with nonresponders (median OS 27.8 vs 13.1 months, p=0.001). Conclusions: Our study demonstrated the significant effects of standard fractionated radiotherapy on systemic Treg levels in melanoma patients. Radiation-induced changes in T-cell subset proportions hold prognostic value. Monitoring of circulating lymphocyte subsets could facilitate personalized combination therapies.

Like living organisms, cancer cells require energy to survive and interact with their environment. Mitochondria are the main organelles for energy production and cellular metabolism. Recently, investigators demonstrated that cancer cells can hijack mitochondria from immune cells. This behavior sheds light on a pivotal piece in the cancer puzzle, the ‘dependence’ on the normal cells. This article illustrates the benefits of new, functional mitochondria for cancer cells that urge them to hijack mitochondria. It describes how functional mitochondria help cancer cells’ survival in the harsh tumor microenvironment, immune evasion, progression, and treatment resistance. Recent evidence has put forward the pivotal role of mitochondria in cancer stem cells’ metabolism. This theory highlights the mitochondria in cancer biology and explains how targeted anti-mitochondrial treatments can improve oncological outcomes.

Phospholipases are a family of lipid altering enzymes that can either reduce or increase bioactive lipid levels. Bioactive lipids elicit signaling responses, activate transcription factors, promote g-coupled protein activity, and modulate membrane fluidity that mediate cellular function. Phospholipases and the bioactive lipids they produce are important regulators on immune cell activity, dictating both pro-inflammatory and pro-resolving activity. During atherosclerosis, pro-inflammatory and pro-resolving activities govern atherosclerosis progression and regression respectively. This review will look at the interface of phospholipase activity, immune cell function, and atherosclerosis.

T-2 toxin produced by fungi of Fusarium genus is highly toxic to human and animals and has been shown to induce apoptosis in various organs/tissues. Apoptosis and autophagy are interconnected processes and these interactions are important for cellular homeostasis as well as pathogenesis. In this study, we report for the first time that T-2 toxin induced autophagy in human liver cells (L02). We showed that T-2 toxin induced the formation of acidic vesicular organelles, concordant with the time and dose-dependent alterations in LC3-phosphatidylethanolamine conjugate (LC3-II) LC3-I/II and p62/SQSTM1 suggesting an enhanced autophagic flux. The T-2 toxin-induced formation of autophagosome and lysosomal fusion was observed by expressing mRFP-GFP-LC3 in L02 cells by lentiviral transduction, and autophagosome was observed by transmission electron microcopy. We found that while T-2 toxin activated both apoptosis and autophagy, activation of autophagy appears to be a leading event reflecting the protective mechanism of cells against the insults by T-2 toxin. Activating autophagy by rapamycin (RAPA) inhibited the apoptosis while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis suggesting the crosstalk of autophagy and apoptosis. In summary, our study showed that activation of autophagy protects liver cells from T-2 toxin-induced apoptosis suggesting autophagy may be targeted for prevention of the T-2 toxin-induced toxicity in human and animals.

Transient receptor potential vanilloid (TRPV) channels act as sensors of pain, temperature, and other external stimuli. We have recently shown that DPV576, an aqueous mixture of nanodiamond (ND) and nanoplatinum (NP), can modulate the activity of TRPV on human primary keratinocytes, suggesting their potential as a possible pain modulator [1]. CD4+ T lymphocytes also express TRPV channels, and we sought with special interest to examine the effect of DPV576 in modulating the functions of TRPV channel expression and secretion of cytokines on human CD4+ T lymphocytes. Human primary CD4+ T cells were activated with anti CD3/CD28 with and without DPV576 at 1:25 and 1:100 dilutions for 24 hours in vitro. TRPV Receptor expression (TRPV1 and TRPV4) on CD4+ T cells was examined by flow cytometry. The capacity of DPV576 to modulate the activity of TRPV1 agonist capsaicin in CD4+ T cells was also determined. Activation of CD4+ T cells was determined by production of cytokines TNF-α, IFN-γ, and IL-10 using specific ELISA kits. DPV576 treatment of CD4+ T cells that were activated with anti CD3/CD28, resulted in increased expression of TRPV1 channel but had no effect on TRPV4. This was accompanied by increased secretion of IFN-g and reduced expression of TRPV1 in capsaicin activated CD4+ T cells. In addition, DPV576 inhibited the capsaicin, induced the production of both IFN-g and TNF-α, and enhanced the secretion of IL-10. We conclude that short term exposure to DPV576 inhibits the activity of TRPV1 channels in CD4+ T lymphocytes, which may suggest its possible beneficial use for pain management.

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.

Bottlenose dolphin (Tursiops truncatus) belongs to the Cetartiodactyla and similarly to the other cetaceans represent the most successful mammalian colonization of the aquatic environment. Here we report a genomic, evolutionary and expression study of Tursiops truncatus T cell receptor beta (TRB) genes. Although the organization of the dolphin TRB locus is similar to that of the other artiodactyl species, with three in tandem D-J-C clusters located at its 3’ end, its uniqueness is given by the reduction of the total length due essentially to the absence of duplications and to the deletions that have drastically reduced the number of the germline TRBV genes. We have analyzed the relevant mature transcripts from two subjects. The simultaneous availability of rearranged TRA and TRB cDNA from the peripheral blood of one of the two specimens, and the human/dolphin amino acids multi sequence alignments, allowed us to calculate the most likely interactions at the protein interface between the alpha/beta heterodimer in complex with major histocompatibility class I (MH1) protein. Interacting amino acids located in the CDR-IMGT of the dolphin variable V alpha and beta domains were identified. According to comparative modelisation, the atome pair contact sites analysis between the human MH1 grove (G) domains and the TR V domains confirms conservation of the structure of the dolphin TR/pMH.

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data shows that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

Extracellular vesicles (EV) are a very heterogeneous group of cell-derived vesicles released by almost all kind of living cells. EV are involved in intercellular communication, both locally and systemically, since they induce signals and transfer their contents (proteins, lipids, RNAs) to other cells, which subsequently trigger a wide variety of biological responses in the target cells. How-ever, cell surface receptor-induced EV release is limited to cells from the immune system, includ-ing T lymphocytes. T cell receptor activation of T lymphocytes induces secretion of EV containing T cell receptor for antigen and several bioactive molecules, including proapoptotic proteins. These EV are thus specific for antigen-bearing cells, which make them ideal candidates for a cell-free, EV-dependent cancer therapy. In this review we discuss the generation of EV by T lymphocytes and some potential therapeutic approaches of these EV.

C-C Chemokine receptor type 5 (CCR5) is expressed on the CD4 T cell surface where CXCR4 and CCR5 expressions are controlled differently during the activation of T cells and with the binding of interleukin type-2 (IL-2). IL-2 can upregulate CCR1 and CCR2 in CD45R01 T cells and increase the T lymphocyte chemotaxis toward CC-chemokines. CD4+ T cells are either apart of the T helper 1 or Th1 lymphocytes that release interferon gamma (IFNγ) and lymphotoxin that provide cellular immunity to internal pathogens and T helper cells type 2 (Th2), which secrete interleukins 4 and 5 (IL-4 and IL-5). IL-4 and IL-5 cause an allergic and humoral immune response to parasites. Th2 lymphocytes use CCR3 chemokine receptors. CCR5 and CXCR3 chemokine receptors are specific for CD4+ Th1 and Th2 lymphocytes. CCR5Δ32 is a 32-base-pair deletion of the CCR5 gene. CCR5 is a co-receptor for the entrance of the human immunodeficiency virus-1 (HIV-1). CCR5Δ32 creates a malfunction of the CCR5 protein that can prevent HIV-1 infection. However, the CCR5Δ32 32-base-pair deletion is not prevalent and predominant in many populations worldwide and there also exist more genetic variations of CCR5 known as CCR5-SNPs. An alternative polymorphism was identified based on the CCR5 gene that was identified as a A to G (A/G) point mutation. This point mutation is located at the 59029 locus on the promoter that lowers the expression rate of CCR5. Gurdol et al. found activity at the promoter of CCR5/590029G was 45% lesser than the CCR5/59029A. The genetic variations of CCR5 SNPs also include: 2459G>SNP of CCR5, C101X, CCR5 gene position at -2273, and the A to G SNP mutation found in two South African blacks. Therefore, more studies are needed to find more and varied chemokine polymorphisms that are present in many diverse populations in the world. The aim of this literature review is to describe the immense impact of CCR5 SNP mutations on viral infection susceptibility, on the pathogenesis of chronic conditions, to endorse the increased discovery of more novel CCR5 SNPs, and to show the significant potential of anti-CCR5 therapies to treat multiple diseased conditions.

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.

Introduction: Obstructive sleep apnea (OSA) is the most common sleep-breathing disorder. OSA is associated with cardiovascular diseases such as coronary artery disease (CAD) and arrhythmias with an increased risk of sudden cardiac death. Some changes in ECG markers are seen as an indicator of arrhythmogenicity, especially ventricular arrhythmias. The goal of this study was to investigate if OSA patients with CAD have QT dispersion and T peak to T end (TpTe) changes as a surrogate of arrhythmogenicity. Methods: We studied 75 patients with CAD who underwent polysomnographic studies. Patients were categorized into mild, moderate, and severe OSA according to the Apnea hypopnea index (AHI). Baseline ECG and echocardiography for assessing LV function and valvular heart disease were done for all of them. Results: Results showed that in patients with moderate and severe sleep apnea QT dispersion was higher in a group with more involvement of coronary artery disease, reduced ejection fraction, and a history of old MI. However, we didn’t find any significant statistical relationship between OSA and TpTe marker. Conclusion: Our results showed a positive relation between ECG arrhythmic indices such as QT dispersion and OSA severity in patients with CAD.

The α(1,2)fucosyltransferase (Se enzyme) encoded by FUT2 is involved in the secretor status of ABH(O) blood group antigens. The sedel2 allele is one of the non-functional FUT2 (se) alleles in which 9.3 kb containing the entire coding region of FUT2 is deleted by Alu-mediated nonhomologous recombination. In addition to this allele, three SNPs of FUT2, c.375A>G, c.385A>T, and c.571C>T, appear to be prevalent in certain Oceanian populations such as Polynesians. Recently, we developed an endpoint genotyping assay to determine the sedel2 zygosity, using a FAM-labeled probe for detection of the sedel2 allele and a VIC-labeled probe for detection of FUT2. In this study, instead of the VIC probe, a HEX-labeled probe covering both c.375A>G and c.385A>T and a Cy5-labeled probe covering c.571C>T were added to the sedel2 allele assay mixture to allow simultaneous detection of these four variations by endpoint genotyping for the sedel2 zygosity and fluorescence melting curve analysis for c.375A>G, c.385A>T, and c.571C>T genotyping. The results obtained from 24 Samoan subjects with this method were identical to those obtained with previous methods. Therefore, it appears that present method can accurately determine these four variations simultaneously.

Immunotherapy has gained great momentum with chimeric antigen receptor T cell (CAR-T) therapy, in which patient’s T lymphocytes are genetically manipulated to recognize tumor-specific antigens increasing tumor elimination efficiency. In the last years, CAR-T cell immunotherapy for hematological malignancies achieved a great response rate on patients and is a very promising therapy for several other malignancies. Each new CAR design requires a preclinical proof-of-concept experiment using immunodeficient mouse models. The absence of a functional immune system in these mice makes them simple and suitable to be mathematically modeled. In this work, we developed a three population mathematical model to describe tumor response to CAR-T cell immunotherapy in immunodeficient mouse models, encompassing interactions between a non-solid tumor and CAR-T cells (effector and long-term memory). We account for several phenomena, such as tumor-induced immunosuppression, memory pool formation, and conversion of memory into effector CAR-T cells in the presence of new tumor cells. Individual donor and tumor specificities were considered as uncertainties in the model parameters. Our model is able to reproduce several CAR-T cell immunotherapy scenarios, with different CAR receptors and tumor targets reported in the literature. We found that therapy effectiveness mostly depends on some specific parameters such as the differentiation of effector to memory CAR-T cells, CAR-T cytotoxic capacity, tumor growth rate, and tumor-induced immunosuppression. In summary, our model can contribute to reduce and optimize the number of in vivo experiments with in silico tests to select specific scenarios that could be tested in experimental research. Such in silico laboratory was made available in a Shiny R-based platform called CARTmath. It is an open-source, easy to run simulator, available at github.com/tmglncc/CARTmath or directly on the webpage cartmath.lncc.br, containing this manuscript results as examples and documentation. The developed model, together with the CARTmath platform, provides potential use for assessing different CAR-T cell immunotherapy protocols and associated efficacy, becoming an accessory towards in silico trials.

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.

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 chronic myeloid leukemia (CML), a clonal proliferative disorder of granulocytic lineage, the 90%‐95% of cases are characterized by t(9;22) (q34.1;q11.2) translocation, leading to the Philadelphia chromosome (1). Rarely, CML patients directly present a blast crisis, mostly of myeloid origin (2, 3). Herein, we describe one rare CML case, showing an unusual early T lymphoid blastic crisis.

We propose that the coexistence of gapless Fermi arcs with the metal-insulator crossover of in-plane resistivity in strongly underdoped cuprates can be explained by the FL* fractionalized Fermi liquid nature of these systems and it is not due simply to disorder effects. The particle excitations of this FL* system derived from variants of the t-J model are: the gapless holon carrying charge with small Fermi momentum proportional to the doping, the gapful spinon carrying spin 1/2, gauge fluctuations coupling them and the hole as a spinon-holon bound state or resonance due to gauge binding with a Fermi surface respecting the topological Luttinger theorem. In our proposal Fermi arcs are determined by the hole resonance, whereas the metal-insulator crossover is dominated by spinon-spinon (with subleading holon-holon) gauge interactions and this dichotomy is able to explain their coexistence.

Radiotherapy for cancer has been known to affect the responses of immune cells, especially those of CD8+ T cells that play a pivotal role in anti-tumor immunity. Clinical success of immune checkpoint inhibitors led to an increasing interest into the ability of radiation to modulate CD8+ T cell responses. Recent studies that carefully analyzed the CD8+ T cell responses following radiotherapy suggest the beneficial roles of radiotherapy on anti-tumor immunity. In addition, numerous clinical trials that evaluate the efficacy of combining radiotherapy with immune checkpoint inhibitors are undergoing. In this review, we summarize the current status of knowledge regarding the changes of CD8+ T cells following radiotherapy from various preclinical and clinical studies. Furthermore, key biologic mechanisms that underlie such modulation, including both direct and indirect effects, are described. Lastly, we discuss the current evidence and essential considerations for harnessing radiotherapy as a combination partner for immune checkpoint inhibitors.

The oncogenicity of the human cytomegalovirus (CMV) is debated to this day. In recent years, mounting evidence addresses an anti-cancer effect via T cell-mediated CMV-targeted tumor de-struction. However, the data mostly comes from single-center studies and in vitro experiments. Broad geographic coverage is required to offer a global perspective. This study examined the correlation between country-specific CMV seroprevalence (n=73) and age-standardized inci-dence rates for 34 tumors using data obtained from the International Agency for Research on Cancer of the World Health Organization. The association between CMV and cancer incidences in 10-year age increments was also analyzed. The study revealed a worldwide inverse correlation between CMV seroprevalence and incidences of 88.2% tumors. Notably, this inverse link persists for all cancers combined (Spearman’s ρ= -0.732, p= 0.001). An antithetical and significant correlation is also observed in particular age groups for the vast majority of tumors. Our results corroborate the conclusions of previous studies and indicate that this phenomenon holds true on a global scale. It applies to a wide spectrum of cancer histologies, suggesting a common under-lying mechanism – CMV-stimulated T cell tumor targeting. Although these results further advance the notion of CMV-based therapies, further in-depth investigation of host-virus interactions is warranted.

The aim of our study was to evaluate the impact of T. gondii status on eosinophils count (PNE), eosinophil to lymphocyte ratio (ELR) and eosinophil to neutrophil to lymphocytes ratio (ENLR) before and after can-nabis cessation in patients with psychiatric disorders. One hundred and eighty-eight patients were includ-ed in the study. T. gondii, PNE, ELR, ENLR, and urinary cannabis were measured at baseline and after 4 weeks of cannabis cessation. Highest PNE (p = .02), ELR (p = .03) and ENLR levels (p = .031) and highest increase of PNE (p = .044), and ENLR (p = .036) levels were found in patients after cannabis cessation only in the Toxo+ group. At four weeks, significant interactions between cannabis and T. gondii status for PNE (p = .038), and for ENLR (p = .043) levels were found, as well as for the evolution between baseline and 4 weeks for ENLR level (p = .049). After cannabis cessation, we found a positive correlation between negative symptoms and PNE levels at 4 weeks in the Toxo+ group. This study shows that the increase of inflammation after cannabis cessation might be modulated by T. gondii seropositivity status in patient after cannabis cessation.

Human Rhinovirus (HRV) is the most common cause of upper respiratory infections and exacerbations of asthma. In this work, we selected 14 peptides (6 from HRV A and 8 from HRV C) encompassing potential CD4 T cell epitopes. Peptides were selected for being highly conserved in HRV A and C serotypes and predicted to bind to multiple HLA II molecules. We found positive T cell recall responses by IFNγ-ELISPOT assays to 8 peptides, validating 7 of them (3 from HRV A and 4 from HRV C) as CD4 T cell epitopes through intracellular cytokine staining assays. Additionally, we verified their promiscuous binding to multiple HLA II molecules by quantitative binding assays. According to their experimental HLA II binding profile, the combination of all these 7 epitopes could be presented and recognized by > 95 % of the world population. We actually determined IFNγ responses to a pool encompassing these CD4 T cell epitopes by intracellular cytokine staining, finding positive responses in 29 out of 30 donors. The CD4 T cell epitopes identified in this study could be key to monitor HRV infections and to develop peptide-based vaccines against most HRV A and C serotypes.

When swine flu vaccines and circulating influenza A virus (IAV) strains are poorly matched, vaccine-induced antibodies may not protect from infection. Highly conserved T cell epitopes may, however, have a disease-mitigating effect. The degree of T cell epitope conservation among circulating strains and vaccine strains can vary, which may also explain differences in vaccine efficacy. Here, we evaluate a previously developed conserved T cell epitope-based vaccine and determine the persistence of T cell epitope conservation over time. We used a pair-wise homology score to define conservation between the vaccine’s swine leukocyte antigen (SLA) class I and II-restricted epitopes and T cell epitopes found in 1,272 swine IAV strains sequenced between 2013 and 2017. Twenty-four of the 48 total T cell epitopes included in the epitope-based vaccine were highly conserved and found in >1,000 circulating swine IAV strains over the five-year period. In contrast, commercial swine IAV vaccines developed in 2013 exhibited declining conservation with the circulating IAV strains over the same five-year period. Conserved T cell epitope vaccines may be useful adjunct for commercial swine flu vaccines and to improve protection against influenza when antibodies are not cross-reactive.

For several years, drugs bearing reactive electrophilic appendages have been developed. These units typically confer prolonged residence time of the drugs on their protein targets, and may assist targeting shallow binding sites and/or improving drug-protein target spectrum. Studies on natural electrophilic molecules have indicated that in many instances natural electrophiles use similar mechanisms to alter signaling pathways. However, natural reactive species are also endowed with other important mechanisms to hone signaling properties that are uncommon in drug design. These include ability to be active at low occupancy and elevated inhibitor kinetics. Here we discuss how we have begun to harness these properties in inhibitor design.

Chimeric antigen receptors (CARs) is one of the curative immunotherapeutic approaches that exploit the antigen specificity and cytotoxicity function of potent immune cells against cancers. Neuroblastoma, the most common extracranial pediatric solid tumors with diverse comportment, could be a promising candidate for using CARs therapies. Several methods harness CARs modified cells in neuroblastoma to increase therapeutic efficiency, albeit the assessment has still been less successful. Regarding the improvement of CARs, various trials have been launched to overcome insufficient capacity. However, the reason behind the inadequate response against neuroblastoma of CARs modified cells are still not well understood. It is essential to update the present reveal of comprehension of CARs to improve the efficiency of CARs therapies. This review summarizes the crucial features of CARs and its design for neuroblastoma, discusses challenges that impact the outcomes of the immunotherapeutic competence, and focuses on devising strategies currently investigated to improve the efficacy of CARs for neuroblastoma immunotherapy.