This paper analyses the viability of different solutions to passively augment the axial stiffness of a horizontal axis radial levitation passive magnetic bearing (PMB) with topology previously studied. The zero-field cooling (ZFC) of high-temperature superconductor (HTS) bulks promotes higher magnetic impulsion and levitation forces and lower electromagnetic losses than with the field-cooling (FC), but on the other hand, the guiding stability is much lower than with FC. Because of stability reasons, FC was adopted in most superconducting maglev systems. The trend of this research group has been to develop an HTS ZFC horizontal axis radial levitation PMB presenting notable levitation forces with reduced electromagnetic losses, defined by a topology that creates guiding stability. Previous work has shown that even optimizing the bearing geometry to maximize magnetic guidance forces, could not be enough to guarantee the axial stiffness required for many applications. First, the extent to which guidance forces are augmented by increasing the number of HTS bulks in the stator is evaluated. Then, the axial stiffness augmentation by passively adding two limiting permanent magnet (PM) rings is evaluated. Results show that the axial stiffness is highly augmented by adding limiting PM rings with no significant additional investment. This change enables using the studied ZFC superconducting PMB in high-precision axial stability applications, such as precision gyroscopes, horizontal axis propellers and turbines.

Space-based gravitational wave detection is extremely sensitive to disturbances. The Keplerian configuration cannot accurately reflect the variations in spacecraft configuration. Planetary gravitational disturbances are one of the main sources. Numerical simulation is an effective method to investigate the impact of perturbation on spacecraft orbits. This study shows that, in the context of the Taiji project, Earth’s gravity is an essential factor in the change in heliocentric formation configuration, contributing to the relative acceleration between spacecrafts in the order of O(10−6)m·s−2. Considering 00:00:00 on October 27, 2032 as the initial orbiting moment, under the influence of Earth’s gravitational perturbation, the maximum relative change in armlengths and variation rates of armlengths for Taiji is 1.6×105km, 32m·s−1 respectively, compared with the unperturbed Keplerian orbit. Additionally, by considering the gravitational perturbations of Venus and Jupiter, the armlength and relative velocity for Taiji are reduced by 16.01% and 17.45%, respectively, compared with when only considering that of Earth. The maximum amplitude of the formation motion indicator changes with the orbit entry time. Results show that the relative velocity increase between the spacecrafts is minimal when the initial orbital moment occurs in July. Moreover, the numerical simulation results are inconsistent when using different ephemerises. The differences between ephemeris DE440 and DE430 are smaller than those between DE440 and DE421.

In Acropora, the complex canals in a coral colony connect all polyps into a holistic network to collaborate in performing biological processes. There are various types of canals, including calice, axial canals, and other internal canals, with structures that are dynamically altered during different coral growth states due to internal calcium transport. However, few studies have considered the regulation of calcium transport in Acropora. In this study, we investigated the morphological changes of the axial canal in six Acropora muricata samples by high resolution micro-computed tomography, observing the patterns of the axial canal during the processes of new branch formation and truncated branch rebuilding. We visualized the formation of a new branch from a calice and deposition of the iconic hexactin skeletons in the axial canal. Furthermore, the diameter and volume changes of the axial canal in truncated branches during rebuilding processes were calculated, revealing that the volume ratio of calcareous deposits in the axial canal exhibit significant increases within the first three weeks, returning to levels in the initial state in the following week. This work indicates that the axial canal can transport calcium to form hexactin skeletons in a new branch and rebuild the tip of a truncated branch. The calcium transport along canal network regulates various growth processes, including budding, branching, skeleton forming, and self-rebuilding of an Acropora colony. Understanding the changes in canal function under normal and extreme conditions will provide theoretical guidance for restoration and protection of coral reefs.

The ratio between blade height and chord, named aspect ratio (AR), plays an important role in compressor aerodynamic design. Once selected, it influences stage performance, blade losses, and the stage stability margin. The choice of the design AR involves both aerodynamic and mechanical considerations, and a reasonable aim is frequently to achieve a desired operating range while maximizing efficiency. For a fixed set of aerodynamic and geometric parameters there will be an optimal choice in AR that achieves a maximum efficiency. However, for a state-of-the-art aero-engine design optimality means multi-objective optimality, that is reaching the highest possible efficiency for a number of operating points while achieving a sufficient stability margin. To this end, the influence of the AR on the performance of the first rotor row of a multistage multi-objective high-speed compressor design is analyzed. A careful setup of the high-speed aerodynamic design problem allows the effect of the AR to be isolated. Close to the optimal AR, only a modest efficiency variation is observed, but a considerable change in compressor stability margin (SM) is noted. Decreasing the AR allows for an increasing efficiency, but at the expense of a reduced surge margin. This allows the designer to trade efficiency for stability. Increasing the AR, however, is shown to reduce both surge margin and efficiency, hence a distinct optimality in stability is observed for the analyzed rotor blade row. In this work, the optimality in surge margin with respect to AR is observed whereas a close to optimal efficiency. The predicted range from AR=1.10 to AR=1.64, is only indicative, considering that the definition of a multi-objective optimality requires balancing efficiency and surge margin and that the choice of balancing these two criteria requires making a design choice along a pareto optimal front.

In Acropora, the complex canals in a coral colony connect all polyps into a holistic network to collaborate in performing biological processes, while axial canal is the largest canal amongst the network and distributes at the center of a coral branch. However, previous studies indicated that, in the non-radial symmetry transport system of Acropora, axial canal do not play a major role in the transport of hydroplasm, and the action of axial canal in coral growth is still obscure. In this study, we reconstructed six Acropora muricata samples by high resolution micro-computed tomography to investigate the growth patterns of axial canals during the processes of new branch forming and truncated branch rebuilding. We found that the axial canal of a new branch is transformed from a calice and the polyps in the new branch are budded from the polyp in the axial canal. Meanwhile, the axial canal can transport the calcareous skeletons to rebuild the tip of a truncated branch, which represents as the change in the diameter of axial canal and calcareous deposition/reduction in it. This work indicate the regulation of axial canal in the growth processes including budding, branching, and mineralising of an Acropora colony.

To realize precise control of the quantum dots (Qdots) device, multi-channel precision bias source plays the key role. In this paper, the 16-channel high precision bias source with 18-bit resolution for Qdots device was designed. The prototype was made and its performance was tested. The short time fluctuations can reach 50μV. The step response time is less than 3μs. The resolution, stability, linearity and dynamic range of the bias source exhibits good performance. What's more, the bias source can be controlled locally and online. The results show that it is one effective and feasible topology for experiments in Qdots device application.

Despite significant advances in metallurgy and the potential to create high and very high-strength steel, all international specifications for steel design provided little information about the limits of slenderness for high-strength steel sections (HSSs) and didn’t give anything about the design of very high-strength steel sections (VHSSs). The American structural steel design specification covers circular hollow sections (CHS) of steel grades up to S690, while it isn't in ANSI/AISC 360-16 and ASTM A514/A514M. Euro code EN 1993-1-1 can be applicable only to steel grades up to S460. EN 1993-1-3 and EN 1993-1-12 contain supplementary rules for cold-formed members and HSS (S460- S700), respectively. Though ductility requirements for (HSS) are specifically established in EN 1993-1-12, it is largely a continuation of the normal-strength-steel design procedures standardized in EN 1993-1-1, where (HSSs) are largely treated as normal-strength steels in these rules, and the same design approaches are used. The behavior of high and very high-strength steel circular hollow sections under axial compression load is studied in this research. A total of 16 nonlinear finite-element (FE) models were generated to replicate stub column tests that were experimentally tested by others in previous research. Hence, a parametric study is conducted using forty FE models developed to investigate the local buckling behavior under various slenderness ratios comprehensively. The developed models cover slenderness ratios ranging from 20 to 1226 and steel grades S460 and S1100 with yield stress equal 460 MPa and 1152 MPa, respectively. The FE results were combined with 105 previously collected experimental results to assess the applicability of existing codified design methodologies in the Euro code and the North American codes of cold-formed CHS. Based on the results of this study, new cross-sectional slenderness limits and new design equations for more efficient simple designs were presented for high and very-high strength steel circular hollow sections and Compared with the results of experimental tests and FE models.

Leaf area estimation is a critical component in the study of plant growth and productivity within agricultural systems. This research introduces the LeafArea package, a specialized tool designed to calculate the leaf area of six distinct Andean fruit species: S. quitoense, S. betaceum, P. peruviana, R. fruticosus, P. ligularis and P. edulis. Leveraging response variables such as species type, leaf length and width, the package employs advanced machine learning algorithms to estimate leaf area accurately. The primary focus of the study is to identify the most effective model for describing the relationship between leaf width, length, and area for each plant species. Currently, the LeafArea package utilizes four different machine learning algorithms, namely generalized linear model (GLM), generalized linear mixed model (GLMM), Random Forest and XGBoost. Among these, XGBoost stands out as a top-performing algorithm, exhibiting exceptional predictive accuracy. The evaluation metrics employed in the program provide valuable insights for researchers, aiding in informed decision-making. Specifically, XGBoost demonstrates significantly lower prediction errors and approaches a near-perfect R2 value, emphasizing its potential to enhance predictive accuracy. These results underscore the efficacy of machine learning techniques, as a compelling choice for researchers seeking precise and robust predictions in leaf area estimation. The LeafArea package thus represents a valuable tool for advancing our understanding of plant growth dynamics, resource allocation, and overall productivity within agricultural ecosystems.

This paper introduces a method to achieve optimal Gaussian estimation even when operating with low precision numerical representations of the full covariance matrix, such as 16-bit integer or 32-bit single precision formats, instead of more expensive double precision floating point representations (64 bits). The approximation's numerical error is accurately estimated in a conservative manner, resulting in minimal covariance inflation. When combined with a compressed estimator like the GCKF (Global Compressed Kalman Filter), which performs global updates at low frequency, this approach produces estimates that are nearly identical to the optimal ones. The deviation between the results obtained using this new approach and those obtained with the standard GCKF (which operates in double precision) is negligible. This new method is particularly relevant in high-dimensional estimation problems that require high-frequency operation. By leveraging the compressed operation of the GCKF, the estimation process applies the necessary approximation only during low-frequency global updates, using the single precision format instead of the more expensive double precision representations. The introduced numerical approximation is accurately estimated while maintaining a conservative approach, resulting in minimal covariance inflation. When combined with the GCKF, which performs global updates at low frequency, the estimates produced are almost identical to the optimal ones. This approach is particularly useful in high-dimensional estimation problems that require high-frequency operation. By representing the full covariance matrix in a low precision numerical format and applying appropriate scaling, memory usage is significantly reduced, offering substantial benefits for high-dimensional estimation problems and enabling real-time smoothing processes in such cases. By reducing the memory requirements for storing the full covariance matrix, the CPU avoids encountering a high number of page faults, resulting in improved processing performance. Lastly, the experimental section verifies the performance of the proposed approach in a single precision (32-bit floating point) GCKF SLAM process, assessing expected values and standard deviations of marginal PDFs.

Novel high energy density materials N14 (1,6-dihydro-1,2,3,3a,4,5,5a,6,7,8,8a,9,10,10a-tetradecazapyrene) and N18 (1,2,2a,3,4,4a,5,6,6a,7,8,8a,9,10,10a,11,12a-octadecazacoronene) were designed, and their structures, detonation performance and stabilities were calculated employing density functional theory (DFT). Calculations reveals that they have a good balance between high energy and stability. Their energy gaps between LUMO and HOMO are all lower than that of TATB, while their impact sensitivity h_50% is estimated close to that of RDX. Concerning energy, detonation performance of the N14 (P = 43.6 GPa, D = 10040 m/s, Q = 2214 cal/g) and the N18 (P = 37.4 GPa, D = 9400 m/s, Q = 2114 cal/g) are comparable to CL-20.

A novel method based on a hybrid incremental modeling approach has been designed and applied to imbalance detection in ultra-high precision rotating machines. The model is obtained by a two-step iterative process that combines an overall model (least-squares fitting) with a local model (fuzzy k-nearest-neighbour) to take advantage of their complementary capacities. Three normalization strategies of evaluating the effect on accuracy are analyzed. A comparative study demonstrates that the hybrid incremental model provides better error-based performance indices for detecting imbalance than a nonlinear regression model and an adaptive neural-fuzzy inference system model. The suitability of Mahanolobis normalization for hybrid incremental modeling is also demonstrated in this case study. The proposed strategy for imbalance detection is simple, fast, and non-intrusive, reducing the deterioration in the performance of ultra-high precision rotating machines due to vibrations.

The purpose of this study was to conduct a meta-analysis that shows the influence of fiber on ultimate compressive strength and tensile strength of ultra-high performance concrete. The internet scholarly search engines and ScienceDirect article references were used to illustrate the papers concerning the experimental investigations of mechanical properties of ultra-high strength concrete with and without fiber with clearly, completely and comparative raw data. The normal concrete test results were dismissed from this search. Seven trials were identified based on the adopted inclusion and exclusion criteria above. The meta-analysis based on standardized mean difference was carried out on the basis of a fixed-effects model for the major outcomes of the ultimate compressive and tensile properties of ultra-high performance concrete. A total of 888 test specimens were enrolled in these seven trials. The combined analysis yielded a sign of a significant improvement in ultimate compressive strength and tensile strength of ultra-high strength concrete with fiber addition of 2% by concrete volume. The summary effect size of ultimate compressive strength was 2.34 while a more improvement in term of tensile strength with effect size of 2.64. By addition fiber of 2% provides a significant benefit in mechanical properties of ultra-high performance concrete.

Phenotypic characterization of crop genotypes is an essential yet challenging aspect of crop management and agriculture research. Digital sensing technologies are rapidly advancing plant phenotyping and speeding-up crop breeding outcomes. However, off-the-shelf sensors might not be fully applicable and suitable for agriculture research due to diversity in crop species and specific needs during plant breeding selections. Customized sensing systems with specialized sensor hardware and software architecture provide a powerful and low-cost solution. This study designed and developed a fully integrated Raspberry Pi-based LiDAR sensor named CropBioMass (CBM), enabled by internet of things to provide a complete end-to-end pipeline. The CBM is a low-cost sensor, provides high-throughput seamless data collection in field, small data footprint, injection of data onto the remote server, and automated data processing. Phenotypic traits of crop fresh biomass, dry biomass, and plant height estimated by CBM data had high correlation with ground truth manual measurements in wheat field trial. The CBM is readily applicable for high-throughput plant phenotyping, crop monitoring, and management for precision agricultural applications.

To improve the understanding of soil–pile interaction of laterally loaded piles, the quasi-static test of pile group foundation in silty clay with 5 foundation piles arranged in cross shape is carried out. The direct measurement-based p–y curves at different depths showed nonlinear behavior, in which the initial stiffness and ultimate soil reaction increased as the depth increased. The loading displacement amplitude corresponding to the failure of each foundation pile in the high axial compression reinforced concrete pile group foundation is given as follows: the front-end nappe foundation pile (#3 pile) is 6mm, the middle pile is 16mm, the front-end nappe foundation pile is 20mm, and the loading displacement amplitude of side pile is 24mm. In silty clay, due to the existence of pile group effect, the edge effect has little effect on the horizontal foundation bed coefficient of foundation pile in pile group, while the influence of masking effect on the horizontal foundation bed coefficient of each foundation pile in pile group is not related to the position of pile, but only to the existence of masking effect, and the influence of different columns of masking effect on the horizontal foundation bed coefficient is the same.

This paper aims to present the basic assumptions for creation of social Fröhlich condensate and attract attention of other researchers (both from physics and socio-political science) to the problem of modelling of stability and order preservation in highly energetic society coupled with social energy bath of high temperature. The model of social Fröhlich condensation and its analysis are based on the mathematical formalism of quantum thermodynamics and field theory (applied outside of physics). The presented quantum-like model provides the consistent operational model of such complex socio-political phenomenon as Fröhlich condensation. The model of social Fröhlich condensation is heavily based on theory of open quantum systems. Its consistent elaboration needs additional efforts. Evidence of such phenomenon as social Fröhlich condensation is demonstrated by stability of modern informationally open societies Approaching the state of Fröhlich condensation is the powerful source of social stability. Understanding its informational structure and origin may help to stabilize the modern society. Application of the quantum-like model of Frhlich condensation in social and political sciences is really the novel and original approach to mathematical modeling of social stability in society exposed to powerful information radiation from mass-media and internet based sources.

The structural stability of γ-boron is investigated using Raman spectra under high pressures up to 126 GPa at ambient temperature. The pressure dependence of all the Raman-active modes of the γ-boron is reported. We also observe amusing changes within the B3g and B1g Raman-active vibrational modes, which results in the phenomenon of merging first and then separating of the Raman peaks. In addition to the Raman measurements, the changes in crystal structure and force constants are calculated to reasonably explain the discrepancy between the two Raman modes in response to pressure. The results of the continuous shifts for all Raman modes with increasing pressure indicate that γ-boron remains stable below this pressure value, with no changes in either symmetry or structure.

Remote sensing technology provides a new way to explore the earth for geoscience applications. In the context of continuous deepening of geological research and the vigorous development of geospatial information science, 3D geological modeling technology has become a research hotspot in the intersection of earth science and information science. The traditional 3D geological modeling technology refers to underground 3D modeling using geological data. This modeling method can only display the underground scene in 3D visualization, but cannot display the surface in detail. In this study, remote sensing technology is adopted to improve the traditional 3D geological modeling method, so that geological modeling can be integrated with remote sensing image, and a new 3D geological modeling method based on remote sensing technology is developed. This method can perform integrated 3D visualization of underground and aboveground scenes, which provides a new way for disaster prevention and reduction, geological prospecting and tectonic interpretation. The new 3D geological modeling method is mainly applied in the geological field, and has made new progress in multi-source heterogeneous geological data fusion, large-scale high-precision modeling, geological grid subdivision, attribute modeling technology, remote sensing image fusion and other aspects. Taking the Ya'an area as an example, this paper makes use of the new generation of 3D geological modeling technology to carry out 3D geological modeling and visual display. The 3D visualization in Ya'an area verifies the feasibility and effectiveness of the new 3D geological modeling method based on remote sensing technology in the current data environment.

High resolution information on nucleotide arrangement in the genome of any or-ganism is critical to understand its genetic makeup, function, and evolutionary his-tory. For years, DNA sequencing has provided crucial breakthroughs in the field of genomics and molecular biology. With the advent of technology, Next Generation Sequencing has now transformed the whole genome sequencing prospects, thus unveiling the novel and interesting features of an organism genome that can behold. Next generation sequencing platforms offer realistic approach to identify and anal-yses whole genome with high throughput, accuracy, scalability in a very short time span. Information obtained can be further used in improving our existing healthcare systems, designing novel and personalized therapeutic modules, making the envi-ronment sustainable and proactively preparing ourselves for future pandemics and outbreaks. This article discusses the various NGS technologies and approaches, their advantages, drawbacks, and futuristic usage in different fields. Though still in nascent stages and marred with flaws, with ongoing advancement, NGS will indeed have promising impacts in the future.

Almond is worldwide consumed and renowned as a valuable healthy food. In spite of this, it is also a potent source of allergenic proteins able to trigger several mild to life-threatening immunoreactions. Food processing proved to alter biochemical characteristics of proteins, thus affecting the respective allergenicity. In this paper we investigated the effect of autoclaving, preceded or not by a hydration step, on the biochemical and immunological properties of almond proteins. Any variation in the stability and immunoreactivity of almond proteins extracted from the treated materials, were evaluated by total protein quantification, ELISA assay and protein profiling by electrophoresis-based separation (SDS-PAGE). The autoclaving alone was found to weakly affect almond proteins stability, despite what observed for the combination of hydration and autoclaving, which resulted in a loss of approximately 70% of total protein content compared to untreated sample, and in a final negligible immunoreactivity, as well. The final SDS-PAGE protein pattern recorded for almonds hydrated and autoclaved disclosed significant changes. In addition, the same samples were further submitted to in vitro simulated gastro-duodenal (GI) digestion to evaluate potential changes induced by these processing on allergens digestibility. Digestion products were identified by HPLC-HRMS/MS analysis followed by software-based data mining, and complementary information were provided by analyzing the proteolytic fragments lower that 6 kDa in size. The autoclave based treatment was found not to alter the allergens digestibility, whereas an increased susceptibility to proteolytic action of digestive enzymes was observed in almonds subjected to the combination of prehydration and autoclaving. Finally, the residual immunoreactivity of the GI resistant peptides was investigated in-silico by bioinformatic tools, confirming that by following both approaches, no epitopes survived the almond digestion, thus demonstrating the potential effectiveness of these treatments to reduce almond allergenicity.

Creep is a fundamental property naturally exists in some types of rock, which is significant for the long-term stability of roadways during the mining process. In this paper, the long-term strength of coal and rock were obtained via laboratory experiments, and a Cvisc elasto-viscoplastic model was adopted and introduced in FLAC3D, based on the 3101 transport roadway in Hongqinghe Coal Mine, to investigate the influence of creep on the stability of deep-high stress roadway. The test results show that the long-term strength of 3-1 coal and sandy mudstone, respectively, is 18.65 MPa, 39.95 MPa. The plastic zone, the deformation, and the damage of roadway surrounding rock behave an obvious increase after being excavated for 720d as the creep model was chosen. The plastic zone failure with models shear-p (1090.7 m3), shear-n (381.7 m3), tension-n (98.4 m3), and tension-p (30.8 m3), the damage value has an obvious increment of increased 21.2% (0.053), the deformation increases in the order is two-sidewalls (1978 mm), roof (907 mm), floor (101 mm). The creep of the roadway can be divided into three stages: the accelerating stage, the decaying stage, and the stable stage. The creep speed of each stage is greatly affected by the presence or absence of anchor spray support: the creep speed of the bare roadway roof, roadway side, and floor stability, respectively, is 1.01, 1.02, and 0.12 mm/d; After anchor spray support, the creep velocity, correspondingly, decreased to 0.69, 0.37, and 0.12 mm/d, and the amount of surrounding rock damage decreased from 0.302 to 0.243. This indicates that the anchor spray support can significantly reduce the creep effect of the roadway. The Cvisc creep model was verified reliable and can provide guidance for deep high-stress coal roadway support.

Curcumin, a nontoxic and cheap natural medicine, has high therapeutic efficacy for many diseases including diabetes and cancers. Unfortunately, its exceedingly low water-solubility and rapid degradation in the body severely limit its bioavailability. In this work, we prepare a series of biocompatible poly(vinyl anisole)@nonlinear poly(ethylene glycol) (PVAS@PEG) core-shell nanogels with different PEG gel shell thickness to provide high water solubility, good stability, and controllable sustained release of curcumin. The PVAS nanogel core is designed to attract and store curcumin molecules for high drug loading capacity and the hydrophilic nonlinear PEG gel shell is designed to offer water dispersibility and thermo-responsive drug release. The obtained nanogels are monodispersed in spherical shape with clear core-shell morphology. The size and shell thickness of the nanogels can be easily controlled by changing the core-shell precursor feeding ratios. The optimized PVAS@PEG nanogels display a high curcumin loading capacity of 38.0 wt%. The nanogels can stabilize the curcumin from degradation at pH =7.4 and release the curcumin in response to heat in the physiologically important temperature range. The nanogels can enter cells effectively and exhibit negligible cytotoxicity to both the B16F10 and HL-7702 cells at a concentration up to 2.3 mg/mL. Such designed PVAS@PEG nanogels have a great potential to be used for delicate drug delivery.

Nowadays, there are implemented devices whose purpose is to perform massive computations by saving resources at the time they reduce the latency of arithmetic operations. These devices are usually GPUs, FPGAs and other specialised devices such as "Coral". Neural networks, digital filters and numerical simulators take advantage of the massively parallel operations of such devices. One way to reduce the amount of resources used is to limit the size of the registers that store data. This has led to the proliferation of numeric formats with a length of less than 32 bits, known as short floating point or SFP. We have developed several SFP’s for use in our neural network accelerator design, allowing for different levels of accuracy. We use a 16-bit format for data transfer and different formats can be used simultaneously for internal operations. The internal operations can be performed in 16-bit, 20-bit and 24-bit. The use of registers larger than 16-bit allows the preservation of fractional information while increasing precision. By leveraging some of the FPGA’s arithmetic resources, our design outperforms designs implemented from scratch and is competitive with specialized arithmetic circuits already implemented in the FPGA.

Pharmacogenetics (PGx) aims to identify the genetic factors that determine inter-individual differences in response to drug treatment maximizing efficacy while decreasing the risk of adverse events. Estimating the prevalence of PGx variants involved in drug response, is a critical preparatory step for large-scale implementation of a personalized medicine program in a target population. Here, we profiled pharmacogenetic variation in fourteen clinically relevant genes in a representative sample set of 1,577 unrelated sequenced Sardinians -- an ancient island population that well accounts for genetic variation in Europe as a whole and, at the same time are enriched in genetic variants that are very rare elsewhere. To this end, we used PGxPOP, a PGx allele caller based on the guidelines created by the Clinical Pharmacogenetics Implementation Consortium (CPIC), to identify the main phenotypes associated with the PGx alleles most represented in Sardinians. We estimate that 99.43% of Sardinian individuals may potentially respond atypically to at least one drug, that on average each individual is expected to have an abnormal response to about 17 drugs, and that for 27 drugs the fraction of the population at risk of atypical responses to therapy is more than 40%. Finally, we highlighted 174 pharmacogenetic variants for which the minor allele frequency is at least 10% higher among Sardinians as compared to other European populations, a fact that may contribute to substantial interpopulation variability in drug response phenotypes. This study provides baseline information for further large-scale pharmacogenomic investigations in the Sardinian population and underlines the importance of the PGx characterization of diverse than European populations as Sardinians.

The biology of aging is focused on the identification of novel pathways that regulate the underlying processes of aging to develop interventions aimed at delaying the onset and progression of chronic diseases to extend lifespan. However, the research on the aging field has been conducted mainly in animal models, yeast, Caenorhabditis elegans and cell culture. Thus, it is unclear to what extent this knowledge is transferable to humans since they might not reflect the complexity of aging in people. Organoid culture is an in vitro 3D cell-culture technology that reproduces the physiological and cellular composition of the tissues and/or organs. This technology is being used in the cancer field to predict the response of a patient-derived tumor to a certain drug or treatment serving as patient stratification and drug-guidance approaches. Modeling aging with patient-derived organoids has a tremendous potential as a preclinical model tool to discover new biomarkers of aging, to predict adverse outcomes during aging and to design personalized approaches for prevention and treatment of aging-related diseases and geriatric syndromes. This could represent a novel approach to study chronological and/or biological aging paving the way to personalized interventions targeting the biology of aging.

The G protein-coupled receptor (GPCR) Smoothened (Smo) is a central signal transducer of the Hedgehog (Hh) pathway which has been linked to diverse forms of tumours. Stimulated by advancements in structural and functional characterisation, the Smo receptor has been recognised as an important therapeutic target in Hh-driven cancers, and several Smo inhibitors have now been approved for cancer therapy. This receptor is also known to be an oncoprotein itself and its gain-of-function variants have been associated with skin, brain, and liver cancers. According to the COSMIC database, oncogenic mutations of Smo have been identified in various other tumours, although their oncogenic effect remains unknown in these tissues. Drug resistance is a common challenge in cancer therapies targeting Smo, and data analysis shows that healthy individuals also harbour resistance mutations. Based on the importance of Smo in cancer progression and the high incidence of resistance towards Smo inhibitors, this review suggests that detection of Smo variants through tumour profiling could lead to increased precision and improved outcomes of anti-cancer treatments.

Precision cancer medicine primarily aims to identify individual patient genomic variations and exploit vulnerabilities in cancer cells to select suitable patients for specific drugs. These genomic features are commonly determined by gene sequencing prior to therapy, to identify individuals who would be most responsive. This precision approach in cancer therapeutics remains a powerful tool that benefits a smaller pool of patients, sparing others from unnecessary treatments. A limitation of this approach is that proteins, not genes, are the ultimate effectors of biological functions, and therefore the targets of therapeutics. An additional dimension in precision medicine that considers an individual’s cytokine response to cancer therapeutics is proposed. Cytokine responses to therapy are multifactorial and vary among individuals. Thus, precision is dictated by the nature and magnitude of cytokine responses in the tumor microenvironment exposed to therapy. This review highlights cytokine responses as modules for precision medicine in cancer therapy, including potential challenges. For solid tumors, both detectability of cytokines in tissue fluids and their being amenable to routine sensitive analyses could address the difficulty of specimen collection for diagnosis and monitoring. Therefore, in precision cancer medicine, cytokines offer rational targets that can be utilized to enhance the efficacy of cancer therapy.

We hypothesized that reticuloruminal temperature and pH, as well as cow activity, can be used as biomarkers for the early diagnosis of clinical mastitis in dairy cows. Therefore, we aimed to detect the relationship between reticuloruminal temperature and pH, cow activity, and clinical mastitis in dairy cows. We randomly selected cows with clinical mastitis and clinical healthy cows (HG) out of 600 milking cows. We recorded the following parameters during the experiment: reticulorumen tem-perature (RR temp.), reticulorumen pH (RR pH), and cow activity. We used smaXtec boluses (smaXtec animal care technology®, Graz, Austria). In this investigation, reticulorumen data ob-tained seven days before diagnosis were compared to HG data from the same time period. CM cows were observed on the same days as the healthy cows. The healthy group’s RR pH was 7.32% higher than that of cows with CM. Reticulorumen temperature was also 1.25% higher in the CM group than in the control group. The healthy group had a higher average value for walking activity and was 17.37% higher than the CM group. The data of reticulorumen pH changes during 24 h showed that during the day, the pH changed from 5.53 to 5.83 in the CM group. By contrast, pH changed from 6.05 to 6.31 in the control group. The lowest reticulorumen pH in the CM group was detected on the third day before diagnosis. It was 15.76% lower than the highest reticulorumen pH detected on the sixth day before diagnosis. The lowest reticulorumen pH in CM cows was detected at 0 and 1 days before diagnosis. It was 1.45% lower than the highest reticulorumen pH detected on the second day before diagnosis. The lowest walking activity in the CM group was detected 0 days before diagnosis, 50.60% lower than on the fifth day before diagnosis. The lowest walking activity was detected 0 days before diagnosis, 39.57% lower than on the seventh day before diagnosis. In this study, we found that reticuloruminal temperature, reticuloruminal pH, and cow ac-tivity could be used as biomarkers for the early diagnosis of clinical mastitis in dairy cows.

Here, we report the prediction of vegetative stages variables of canary bean crop by means of RGB and multispectral images obtained from UAV during the ripening stage, correlating the vegetation indices with biometric variables measured manually in the field. Results indicated a highly significant correlation of plant height with eight RGB image vegetation indices for the canary bean crop, which were used for predictive models, obtaining a maximum correlation of R2 = 0.79. On the other hand, the estimated indices of multispectral images did not show significant correlations.

Site Index has been widely used as an age normalised metric to account for variation in forest height at a range of spatial scales. Although previous research has used a range of modelling methods to describe regional variation in Site Index little research has examined gains that can be achieved through use of regression kriging or spatial ensemble methods. In this study an extensive set of environmental surfaces were used as covariates to predict Site Index measurements covering the environmental range of \textit{Pinus radiata} D. Don plantations in Chile. Using this dataset, the objectives of this research were to (i) compare predictive precision of a range of geostatistical, parametric and non-parametric models, (ii) determine if significant gains in precision can be attained through use of regression kriging, (iii) evaluate the precision of a spatial ensemble model that utilises predictions from the five most precise models, through using the model prediction with lowest error for a given pixel and (iv) produce a map of Site Index across the study area. The five most precise models were all geostatistical and included ordinary kriging and four regression kriging models that were based on partial least squares or random forests. A spatial ensemble model constructed from these five models was the most precise of those developed (RMSE = 1.851 m, RMSE% = 6.38%) and had relatively little bias. Climatic and edaphic variables were the strongest determinants of Site Index and in particular, variables related to soil water balance were well represented within the most precise predictive models. These results highlight the utility of predicting Site Index using a range of approaches, as these can be used to construct a spatial ensemble that may be more precise than predictions from the constituent models.

Tumour necrosis factor-α is a key mediator of inflammation in rheumatoid arthritis its discovery led to the development of highly successful anti-TNF therapy. Subsequently, other biologic drugs targeting immune pathways, namely interleukin-6 blockade, B cell depletion, and T cell co-stimulation blockade, have been developed. Not all patients respond to a biologic drug leading to a knowledge gap between biologic therapies available and the confident prediction of response. So far, genetic studies have failed to uncover clinically informative biomarkers to predict response. Given that the targets of biologics are immune pathways, immunological study has become all the more pertinent. Furthermore, advances in single cell technology have enabled the characterisation of many leucocyte subsets. Studying the blood immunophenotype may therefore define biomarker profiles relevant to each individual patient’s disease and treatment outcome. This review summarises our current understanding of how immune biomarkers might be able to predict treatment response to biologic drugs.

Sample size using prevalence has been one of the most important medical research methodologies and has been used in original articles more often than any other statistical tool available. The simple formula consists of variables interdependent and it is as important to understand how they influence each other as it is to learn to use the formula to calculate the sample size. With the choice of different amounts of precision and levels of confidence available to a medical researcher, it should be of paramount importance to understand what a slight change in choosing the parameter would mean at the end of the research. Understanding of different Z values, Levels of precision, and ranging Prevalence is required to understand the effect on the sample size and subsequently on the research. Topological representation using parameter ranges can be used to demonstrate this relationship.

Vaccination represents the historical milestone in medical sciences, which has been saving millions of lives. Nonetheless, continued outbreaks of emergent infectious diseases are swamping from every coast to every border all over the world. Modern vaccines are our most powerful arsenals to defend the public health of a global population ever since 1796. As unexpected, modern vaccination approaches have brought out all sorts of unwelcome pathogenic disorders to varying extents. Pathogenic viruses have also continued to evolve to defeat elaborate arsenals devised by human intelligence. In this review, we have covered a variety of vaccination approaches along with their sophisticated materials from the past to the most recent development. Furthermore, we discuss varied serious pathogenic outcomes elicited by contemporary vaccination programmes involving novel materials in real clinical trials. The complex immune mediators will be discussed in the context to tackle the complication of vaccine-induced pathogenesis. We will offer the insight into the intractable discrepancy of vaccine-associated pathology. The precision approach bestowed with evolutionary concepts will be considered as a feasible option to confront various issues of pathogenic complicacy.

The production of high-quality wines is one of the primary goals of modern oenology. In this regard, it is known that the potential quality of a wine begins to be determined in the vineyard, where the quality of the grape, initially, and later that of the wine, will be influenced by the soil properties. Given the spatial variability of the fundamental soil properties related to the potential grape production, such as texture, soil organic matter content, or cation exchange capacity, it seems that a uniform management of a vineyard is not the most optimal way to achieve higher grape quality. In this sense, the delineation of zones with similar soil characteristics to implement site-specific management is essential, reinforcing the interest to incorporate technologies and methods to determine these homogeneous zones. A case study was conducted in a 3.3 ha vineyard located near Évora, South of Portugal. A non-contact sensor (DUALEM 1S) was used to measure soil apparent electrical conductivity (ECa) in the vineyard, and later, a kriged ECa map was generated. ECa and elevation maps were utilised to delineate homogeneous zones (management zones, MZs) in the field through a clustering process. MZs were validated using some soil properties (texture, pH, organic matter -OM, phosphorous -P2O5, potassium -K2O, sum of the exchange bases -SEB; and cation exchange capacity -CEC) which were determined from 20 soil samples taken in the different MZs. Additionally, validation was also performed using Rasch measures, which were defined based on the formula-tion of the objective and probabilistic Rasch model, integrating the information from the afore-mentioned soil properties at each sampling location. The comparison of the MZs was more evident with the use of the Rasch model, as only one value was to be employed in each MZ. The use of ECa constitutes an efficient technological tool for implementing site-specific man-agement in viticulture, which allows for the improvement of decision-making processes by con-sidering the inherent spatial variability of the soil.

This study examines the impact of alcohol concentration on the precision of unmanned aerial vehicle (UAV) operations. While the impact of alcohol impairment on various activities is well documented, its specific influence on drone piloting accuracy remains less studied. To address this, we carried out empirical research using an original methodology and a real-world environment. The study involved a group of 35 participants performing a series of flights using a selected drone (DJI Mavic2 Pro) on a bespoke obstacle route. Between each flight series, participants consumed a measured amount of alcohol, designed to incrementally increase their blood alcohol concentration monitored via breath tests. The precision of the drone pilot was evaluated by comparing various parameters from successive test flights, such as time, distance, average speed, and incident frequency, against a baseline trial executed with zero alcohol concentration. Our results indicate a noticeable decline in UAV piloting precision corresponding with increasing alcohol concentration. Parameters such as flight time, distance, speed, and incident frequency all demonstrated this trend. We conclude that alcohol consumption detrimentally affects the accuracy of drone operations. These findings underscore the need for clear policies and guidelines regarding the operation of UAVs under the influence of alcohol.

Asthma is a prevalent disease that around 300 million worldwide, resulting in substantial morbidity, mortality, and economic burden on a global scale. New clinical and laboratory research has shed light on the immunology causing asthma. Asthma is now recognized as a heterogeneous disease. A personalized medicine is based on the classification of asthma by endotype by linking observable characteristics to immunological mechanisms. Identifying endotype mechanisms is essential for better characterizing patients and personalizing therapeutic approaches with novel biological agents that target specific immune pathways. This article provides a summary of the major immunological mechanisms involved in the pathogenesis and emergence of the disease's phenotypic features, as well as the individualized treatment for severe asthma subtypes

Primary Biliary Cholangitis (PBC) is a chronic, cholestatic liver disease with a heterogeneous presentation, symptomatology, disease progression, and response to therapy. The current risk stratification assessment, aimed at identifying patients with a higher risk of disease progression, encompasses an in-depth analysis of demographic data, clinical and laboratory findings, antibody profiles, and the evaluation of liver fibrosis using both invasive and non-invasive techniques. Treatment response scores after one year of therapy remain to date a major factor influencing the prognosis of PBC patients. While the initial therapeutic approach with ursodeoxycholic acid (UDCA) is universally applied, new second-line treatment options have recently emerged, with many others under investigation. Consequently, the prevailing one-size-fits-all approach is poised to be supplanted by tailored strategies, ensuring high-risk patients receive the most appropriate treatment regimen from diagnosis. This will require the development of a risk prediction model to assess, at the time of diagnosis, the course, outcome, and response to first and additional treatments of PBC patients. This manuscript provides a comprehensive overview of the current and emerging tools used for risk stratification in PBC and speculates on how these developments might shape the disease landscape in the near future.

Profitability is an underestimated concept in precision agriculture. In this research, a new module is developed within a pre-existing farm management system to assess the profitability of precision agriculture applications in extended crops. The module is regulated on a 5-meter spatial resolution, thus allowing scaling up of original and processed data on a zone-, field-, cultivar-, and farm-scale. A bottom-up approach, taking advantage of the full functionality of the farm management system, together with a flexible architecture and an easy-to-use interface, renders the new module an innovative commercial application.

Diabetes and diabetes-induced micro and macrovascular complications are major causes of healthcare problems. The extracellular vesicles are produced by all cells from all organisms. They are shown to have properties of the producer cells and also reflect the host physiology and pathology. Since the EVs represent the cellular state they are excellent biomarkers. In this review, we will focus on the EVs produced by the Neuro Vascular Unit cells of the eye as well as the extraocular cells in the onset and progression of diabetic retinopathy. A brief account of the use of these nanovesicles in personalised medicine is also given.

A strategy to reduce qualitative and quantitative losses in crop-yields refers to early and accurate detection of insect-damage caused in plants. Remote sensing systems like hyperspectral proximal sensors are a promising strategy for managing crops. In this aspect, machine learning predictions associated with clustering techniques may be an interesting approach mainly because of its robustness to evaluate high dimensional data. In this paper, we model the spectral response of insect-herbivory-damage in maize plants and propose an approach based on machine learning and a clustering method to predict whether the plant is herbivore-attacked or not using leaf reflectance measurements. We differentiate insect-type damage based on the spectral response and indicate the most contributive wavelengths to perform it. For this, we used a maize experiment in semi-field conditions. The maize plants were submitted to three different treatments: control (health plants); plants submitted to Spodoptera frugiperda herbivory-damage, and; plants submitted to Dichelops melacanthus herbivory-damage. The leaf spectral response of all plants (controlled and submitted to herbivory) was measured with a FieldSpec 3.0 Spectroradiometer from 350 to 2500 nm for eight consecutive days. We evaluated the performance of different learners like random forest (RF), support vector machine (SVM), extreme gradient boost (XGB), neural networks (MLP), and measured the impact of a day-by-day analysis into the prediction. We proposed a novel framework with a ranking strategy, based on the accuracy returned by predictions, and a clusterization method based on a self-organizing map (SOM) to identify important regions in the reflectance measurement. Our results indicated that the RF-based framework algorithm is the overall best learner to deal with this type of data. After the 5th day of analysis, the accuracy of the algorithm improved substantially. It separated the three treatments into different groups with an F-measure equal to 0.967, 0.917, and 0.881, respectively. We also verified that the most contributive spectral regions are situated in the near-infrared domain. We conclude that the proposed approach with machine learning methods is adequate to monitor herbivory-damage of S. frugiperda and stink bugs like Dichelops melacanthus in maize, differentiating the types of insect-attack early on. We also demonstrate that the framework proposed for the analysis of the most contributive wavelengths is suitable to highlight spectral regions of interest.

Accurate expression of bracket prescription is important for successful orthodontic treatment. The aim of this study was to evaluate the accuracy of digital scan images of brackets produced by four different intraoral scanners (IOSs) in terms of the height, position, and angle of the bracket slot when scanning the surface of dental model attached with bracket materials made from different composition of materials. Brackets made from stainless steel, polycrystalline alumina, composite and composite/stainless steel slot were considered, which have been scanned from 4 different IOSs (Primescan, Trios, CS3600 and i500). SEM images were used as references. Each bracket axis was set in the reference scan image, and the axis was set identically by superimposing with the IOS image, and then only the brackets were divided and analyzed. The difference between the manufacturer's nominal torque and bracket slot base angle was 0.39 in SEM, 1.96 in Primescan, 2.04 in Trios, and 5.21 in CS3600 (P <0.001). The parallelism, which is the difference between the upper and lower angles of the slot wall, was 0.55 in SEM, 7.55 in Primescan, 6.74 in Trios3, 6.59 in CS3600, and 24.95 in i500 (p <0.001). This study evaluated the accuracy of the bracket only and it must be admitted that there is some error in recognizing slots through scanning in general

This work introduces a device for long term systematic monitoring of trees against borers. A widely applied way to detect wood-boring insects is to insert a piezoelectric probe with uncoated waveguide in the tree trunk and listen for locomotion or feeding sounds through headphones. This approach has several shortcomings: a) frequent manual inspection of trees is costly and impractical to be scaled to hundreds or thousands of trees, b) the larvae could be present but inactive during the inspection time and, c) when the trees are in urban environments the background noise can be significant and can mask the feeble sounds of wood-boring insects even with the use of specialized headphones. We introduce a remotely controlled device that records and wirelessly transmits on a scheduled basis short recordings of the internal vibrations of a tree to a server. The user can listen remotely or process the recording automatically to infer the infestation state of the tree with wood-boring insects that feed or move inside the tree. When integrated within the IoT framework this device can scale up to automatically monitoring the trees of the entire city. The proposed approach led to detection results in field trials of the pests Xylotrechus chinensis and Rhynchophorus ferrugineus.

The primary measure of the quality of sea surface temperature (SST) fields obtained from satellite-borne infrared sensors has been the bias and variance of matchups with co-located in-situ values. Because such matchups tend to be widely separated, these bias and variance estimates are not necessarily a good measure of small scale (several pixels) gradients in these fields because one of the primary contributors to the uncertainty in satellite retrievals is atmospheric contamination, which tends to have large spatial scales compared with the pixel separation of infrared sensors. Hence, there is not a good measure to use in selecting SST fields appropriate for the study of submesoscale processes and, in particular, of processes associated with near-surface fronts, both of which have recently seen a rapid increase in interest. In this study, two methods are examined to address this problem, one based on spectra of the SST data and the other on their variograms. To evaluate the methods, instrument noise was estimated in Level-2 VIIRS and AVHRR SST fields of the Sargasso Sea. The two methods provided very nearly identical results for AVHRR: along-scan values of approximately 0.18 K for both day and night and along-track values of 0.21 K also for day and night. By contrast, the instrument noise estimated for VIIRS varied by method, scan geometry and day-night. Specifically, daytime, along-scan (along-track), spectral estimates were found to be approximately 0.05 K (0.08 K) and the corresponding nighttime values of 0.02 K (0.03 K). Daytime estimates based on the variogram were found to be 0.08 K (0.10 K) with the corresponding nighttime values of 0.04 K (0.06 K). Taken together: AVHRR instrument noise is significantly larger than VIIRS instrument noise, along-track noise is larger than along-scan noise and daytime levels are higher than nighttime levels. Given the similarity of results and the less stringent preprocessing requirements, the variogram is the preferred method although there is a suggestion that this approach overestimates the noise for high quality data in dynamically quiet regions. Finally, simulations of the impact of noise on the determination of SST gradients show that on average the gradient magnitude for typical ocean gradients will be accurately estimated with VIIRS but substantially overestimated with AVHRR.

This paper presents the PEnsemble 4 model, a sophisticated machine learning framework that integrates IoT-based environmental data to accurately forecast maize yield. With the projected significant growth in global maize demand over the next decade, the inherent risks posed by the crop’s dependence on weather conditions necessitate improved prediction capabilities. The PEnsemble 4 model, developed with high accuracy, incorporates comprehensive datasets encompassing soil attributes, nutrient composition, weather conditions, and UAV-captured vegetation imagery. By employing a combination of Huber and M estimates, the PEnsemble 4 model effectively analyzes temporal patterns in vegetation indices, specifically CIre and NDRE, which serve as reliable indicators of canopy density and plant height. In addition, this research significantly contributes to precision agriculture by offering an efficient and sustainable alternative to conventional farming practices through precise yield predictions. Notably, the PEnsemble 4 model enables earlier estimation, advancing the timeline for yield prediction from the conventional day 100 in the R6 stage to day 79 in the R2 stage. This improvement enhances decision-making processes in farming operations. The remarkable accuracy rate of 91% underscores the importance of adopting a multifaceted data approach that harnesses IoT-derived environmental insights. Additionally, the PEnsemble 4 model extends its benefits beyond yield prediction, facilitating the detection of water and crop stress, as well as disease monitoring in broader agricultural contexts. Ultimately, the PEnsemble 4 model establishes a new standard in maize yield prediction, revolutionizing crop management and protection through the synergistic utilization of IoT and machine learning technologies.

Over the last two decades, a considerable amount of equipment has been acquired (spreaders, seeders, sprayers, among others) to respond to the challenges of Precision Agriculture (PA) concept. Most of this equipment has been purchased at a high cost. However, many of them, despite still being functional and equipped with sensors, actuators, and electronic processing units capable of adjusting to variations in speed, have become obsolete in terms of communication, and incompatible with new monitoring and control systems based on the “Isobus” protocol. This work aims to present a solution for updating the control system (“Ferticontrol”) of a “Vicon RS-EDW” spreader with variable rate application (VRA), making it compatible with the “InCommand” system from “Ag Leader”. The solution includes low-cost “Arduino” and “Raspberry Pi” microcontrollers and open-source software. The development shows that it is possible to implement a solution that is accessible to farmers in general. It also provides a niche business opportunity for young researchers to set up small technology-based enterprises associated with universities and research centers. These partnerships guarantee permanent innovation and represent a decisive step towards modern, technological, competitive, and sustainable agriculture.

In this work, we explore new constraints on phantom scalar field cosmologies with a scalar field employing early times catalogues related to CMB measurements, along with the local standard observables, like Supernovae Type Ia (SNIa), H(z) measurements (Cosmic Clocks), and Baryon Acoustic Oscillations (BAO) baselines. In particular, we studied a tracker phantom field with hyperbolic polar coordinates that have been proposed in the literature. The main goal is to obtain precise cosmological constraints for H0 and σ8, in comparison to other constructions that present tension in early cosmological parameters. Our results show that phantom scalar field cosmologies have a reduced statistical tension on H0 that it is less than 3σ using model-independent CMB catalogues as SPT-3G+WMAP9 and ACTPol DR-4+WMAP9 baselines. This suggests these models using a different phantom potential might address the Hubble constant problem and reduce the systematics involved.

Significant advances in Penning trap measurements of atomic masses and mass ratios of the proton, deuteron, triton, helion, and alpha-particle have occurred in the last five years. These include a measurement of the mass of the deuteron against 12C with 8.5 x 10-12 fractional uncertainty; resolution of vibrational levels of H2+ as mass and the application of a simultaneous measurement technique to the H2+/D+ cyclotron frequency ratio, yielding a deuteron-proton mass ratio at 5 x 10-12; new measurements of HD+/3He+, HD+/T+ and T+/3He+ leading to a tritium beta-decay Q-value with an uncertainty of 22 meV, and atomic masses of the helion and triton at 13 x 10-12; and a new measurement of the mass of the alpha-particle against 12C at 12 x 10-12. Some of these results are in strong disagreement with previous literature values. Their impact in determining a precise proton/electron mass ratio and electron atomic mass from spectroscopy of the HD+ molecular ion is also discussed.

Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases that involve in regulation of cell proliferation, survival, and development. FGFR alterations including amplifications, fusions, rearrangements, and mutations can result downstream activation of tyrosine kinases leading to tumor development. Targeting those FGFR alterations has shown to be effective in cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid neoplasms and there are currently four FGFR inhibitors approved by the Food and Drug Administration (FDA). There have been developments of multiple agents targeting FGFR pathway including selective FGFR inhibitors, ligand traps, monoclonal antibodies, and antibody drug conjugates. However, most of these agents have variable and low responses with some intolerable toxicities and acquired resistances. This review will summarize previous clinical experiences and current developments of agents targeting FGFR pathway and discuss future directions of FGFR targeting agents.

Radiomics refers to the extraction and analysis of a wide range of medical imaging features in a non-invasive and cost-effective manner to comprehensively characterise tumours. In this study, machine learning models combining radiomics and clinical factors were developed to predict retroperitoneal lymph node metastasis in testicular germ cell tumours (TGCTs), with the aim of reducing unnecessary treatment in this group of young patients. Ninety-one patients with surgically proven testicular germ cell tumours and contrast-enhanced CT were included in this retrospective study. After segmenting 273 retroperitoneal lymph nodes using dedicated radiomics software, we developed machine-learning prediction models using Random Forest (RF), Light Gradient Boosting Machine (LGBM), Support Vector Machine Classifier (SVC), and K-Nearest Neighbours (KNN). For each classifier, we developed a radiomics-only, clinical-only, and combined radiomics-clinical prediction model. The models’ performances were evaluated using the area under the receiver operating characteristic curves (AUCs). The RF-based combined clinical and radiomic model showed the most robust performance in predicting LNM with an area under the curve (AUC) of 0.95 (±0.03; 95% CI), accuracy 87%, precision 89%, recall 86% and F1 score 87%, followed by the LGBM model with an area under the curve (AUC) of 0.93 (±0.05; 95% CI), accuracy 83%, precision 87%, recall 80% and F1 score 82%. Decision curve analysis demonstrated the clinical utility of our proposed RF-based combined clinical–radiomics model. Our study has identified reliable and predictive machine-learning techniques for predicting lymph node metastasis in early-stage testicular cancer. Identifying the most effective machine-learning approaches for predictive analysis based on radiomics integrating clinical risk factors can expand the applicability of radiomics in precision oncology and cancer treatment. Multi-centre validation is required to provide high-quality evidence for clinical application.

The fight against suicide is highly challenging as it may be one of the most complex and at the same time most threatening among all psychiatric phenomena. In spite of its huge impact, and despite advances in neurobiology research, understanding and predicting suicide remains a major challenge for both researchers and clinicians. To be able to identify those patients who are likely to engage in suicidal behaviors and identify suicide risk in a reliable and timely manner, we need more specific, novel biological and genetic markers/indicators to develop better screening and diagnostic methods, and in the next step to utilize these molecules as intervention targets. One such potential novel approach is offered by our increasing understanding of the involvement of neuroinflammation based on multiple observations of increased proinflammatory states underlying various psychiatric disorders including suicidal behavior. The present paper overviews our existing understanding of the association between suicide and inflammation including peripheral and central biomarkers, genetic and genomic markers, and our current knowledge of intervention in suicide risk using treatments influencing inflammation, also overviewing the next steps to be taken and obstacles to be overcome before we can utilize cytokines in the treatment of suicidal behavior.

Aluminum alloy (Al6061) sheet micro-hole processing is extensively used in smartphones, tablet PC, and smart wearable devices. The micro-hole processing is commonly performed using laser, micro drilling, microstamping, micro discharge, and chemical etching technologies. Micro-stamping technology is characterized by precision and rapid processing, but the precision positioning of the punch head and lower die is one of the major difficulties in micro-hole stamping, especially in manufacturing array micro-holes. This study used stamping without die technology. This technology uses an array punch head to punch the lower die holes on the base, then performs array micro-hole stamping. The experimental results show that a micro-hole array with 37 micro-holes were successfully manufactured and can be reproduced many times. Tapered array micro-holes with a high aspect ratio can be manufactured using this stamping without die technology; the micro-hole depth can be 260μm, the inlet diameter is 116μm, and the outlet diameter is 25μm. This study has successfully developed the feasibility of array micro-hole stamping technology.

Agricultural production needs technologies that assist the management of natural resources, for example, the collection of real-time data on soil, water, weather, crops, and biodiversity conditions. Sensor technology solutions and open-source software are appropriate for promoting more sustainable agricultural production. Among the advantages of using open-source technologies and software is its potential for extension, collaboration, customization, flexibility, maintenance cost, transparency, speed, and better security. Given the above, the objective of this research was to find, in different electronic databases, exclusively open-source software for precision agriculture, offering a systematic review, and addressing considerations and challenges. This survey considers up-to-date open-source software available in repositories such as GitHub and GitLab, to understand its characteristics and application formats.

The aim of the current study was to determine the relation between subclinical mastitis and rumination behavior registered with an online sensor system. According to the results of the general clinical examination of 650 milking cows, 10 cows with subclinical mastitis (SCM) and 10 clinical healthy cows (HG) were selected (without clinical signs of any diseases). Rumination behavior biomarkers were registered with RumiWatch noseband sensor (RWS; ITIN + HOCH GmbH, Fütterungstechnik, Liestal, Switzerland). Sensors were implanted on the first day after calving. Data from the RWS from 13th days before the diagnosis and 13 days after diagnosis of SCM were used to compare with HG data during the same period. The healthy cows were monitored during the same days as the SCM cows.

Abstract: Early assessment of crop development is a key aspect of precision agriculture. Shortening the time of response before a deficit of irrigation, nutrients and damage by diseases is one of the usual concerns in agriculture. Early prediction of crop yields can increase profitability in the farmer's economy. In this study we aimed to predict the yield of four maize commercial hybrids (Dekalb7508, Advanta9313, MH_INIA619 and Exp_05PMLM) using remotely sensed spectral vegetation indices (VI). A total of 10 VI (NDVI, GNDVI, GCI, RVI, NDRE, CIRE, CVI, MCARI, SAVI, and CCCI) were considered for evaluating crop yield and plant cover at 31, 39, 42, 46 and 51 days after sowing (DAS). A multivariate analysis was applied using principal component analysis (PCA), linear regression, and r-Pearson correlation. In the present study, highly significant correlations were found between plant cover with VIs at 46 (GNDVI, GCI, RVI, NDRE, CIRE and CCCI) and 51 DAS (GNDVI, GCI, NDRE, CIRE, CVI, MCARI and CCCI). The PCA indicated a clear discrimination of the dates evaluated with VIs at 31, 39 and 51 DAS. The inclusion of the CIRE and NDRE in the prediction model contributed to estimate the performance, showing greater precision at 51 DAS. The use of RPAS to monitor crops allows optimizing resources and helps in making timely decisions in agriculture in Peru.

The use of biomarkers to measure immune responses in serum is crucial for understanding population-level exposure and susceptibility to human pathogens. Advances in sample collection, multiplex testing, and computational modeling are transforming serosurveillance into a powerful tool for public health program design and response to infectious threats. In July 2018, 70 scientists from 20 countries met to perform a landscape analysis of approaches that support an integrated serosurveillance platform, including the consideration of issues for successful implementation. Here, we summarize the group’s insights and proposed roadmap for implementation, including objectives, technical requirements, ethical issues, logistical considerations, and monitoring and evaluation.

BACKGROUND: Glioblastoma (GBM) is driven by various genomic alterations. Next generation sequencing (NGS) could yield targetable alterations that may impact outcomes. The goal of this study was to describe how NGS can inform targeted therapy (TT) in this patient population. METHODS: The medical records of patients (pts) with a diagnosis of GBM from 2017-2019 were reviewed. Records of patients with recurrent GBM and genomic alterations were evaluated. Objective response rates and disease control rates were deter-mined. RESULTS: A total of 87 pts with GBM underwent NGS. Forty percent (n = 35) were considered to have actionable alterations. Of the 35, 40% (n=14) pts had their treatment changed due to an alteration. The objective response rate (ORR) of this population was 43%. The disease control rate (DCR) was 100%. The absolute mean decrease in contrast enhancing disease was 50.7% (95% CI 34.8 – 66.6). CONCLUSION: NGS for GBM, particularly in the recurrent setting, yields a high rate of actionable alterations. We observed a high ORR and DCR, reflecting the value of NGS in deciding on TT to match alterations that are likely to respond. In conclusion, patient selection and availability of NGS may impact outcomes in select pts with recurrent GBM.

Concomitant neuropathological hallmarks of Alzheimer’s Disease (AD) are common in the brains of people with Parkinson’s disease (PD). Furthermore, AD biomarkers are associated with cognitive decline and dementia in PD patients during life. Here, we highlight the considerable overlap between AD and PD, emphasizing neuropathological, biomarker, and mechanistic studies. We suggest that precision medicine approaches may successfully identify PD patients most likely to develop concomitant AD. The ability to identify PD patients at high risk for future concomitant AD in turn provides an ideal cohort for trials of AD-directed therapies in PD patients, aimed at delaying or preventing cognitive symptoms.

Colorectal cancer prognosis get worse with advancement of disease into metastatic stage. There is a pertinent need to develop prognostic biomarkers that can be used for personalized and precision medicine. Alternative splicing provides an insight into understanding of changes at isoform expression level which may not be evident at gene level. In this direction, we utilized our prior knowledge about significant alternatively spliced genes and chose ADAM12 and MUC4 for further characterization in a metastatic cell line model. These genes were found to be good prognostic indicators in The Cancer Genome Atlas database. We studied the gene organization and designed primers to specifically amplify a group of isoforms. Differential expression of these group of isoforms was observed in normal, primary and metastatic colorectal cancer cell lines. We further validated the results using sanger sequencing. Isoform expression was found to respond to the 5-fluorouracil treatment. RNAseq analysis of the cell lines further validated the differential expression of gene isoforms. Successful detection of ADAM12 and MUC4 in cell lysates varied according to the antibody used which may reflect differential expression of isoforms. This comprehensive study underscores the importance of studying alternatively spliced isoforms and their probable used as prognostic or predictive biomarkers.

The rising world population has made it imperative to get rid of time-consuming and non-economical agricultural practices. Thus, advances in Internet of Things (IoT) technology have recently propelled significant advancements in agriculture, similar to several other sectors. Through the combination of IoT and Farm Management Information Systems (FMIS), field data can be automatically collected, stored, analysed and accessed by farmers in real-time. In this paper, we present Proof-of-Concept (PoC) IoT circuit and FMIS web app for precision agriculture. The IoT circuit incorporates sensors, microcontroller and Wi-Fi module, which acquire and transfer field data to the FMIS web app. We designed and simulated the IoT circuit using Proteus, Arduino Uno, and Arduino Integrated Development Environment (IDE). The FMIS PoC web app was modelled with relevant Unified Modeling Language (UML) diagrams and Django (a Python framework) was employed to implement the app. Our simulation result illustrates how essentila field parameters can be monitored remotely and seamlessly by agriculture practitioners. It further provides a blueprint for real-time precision agriculture at scale and could serve as a learning aid for students in engineering and agricultural science.

Georeferencing using ground control points (GCPs) is the most common strategy in photogrammetry modeling using UAV-acquired imagery. However, with the increased availability of UAVs with onboard GNSS RTK, georeferencing without GCPs is a promising alternative. However, systematic elevation error remains a problem of this technique. We aimed to analyze the reasons for this systematic error and propose strategies for the elimination of this error. Multiple flights differing in the flight altitude and image acquisition axis were performed at two real-world sites. A flight height of 100m with vertical (nadiral) image acquisition axis was considered primary, supplemented with flight altitudes of 75 m and 125 m with vertical image acquisition axis and two flights at 100 m with oblique image acquisition axes (30° a 15°). Each of these flights was performed twice to produce a full double grid. Models were calculated from individual flights and their combinations. The elevation error from individual flights or even combinations yielded systematic elevation errors of up to several decimeters. This error was linearly dependent on the deviation of the focal length from the reference value. A combination of two flights from the same altitude (with nadiral and oblique image acquisition) was capable of reducing the systematic elevation error to less than 0.03 m. This study is the first to demonstrate the linear dependence between the systematic elevation error of the models based only on the onboard GNSS-RTK data and the deviation in the determined internal orientation parameters (focal length). Besides, we have shown that a combination of two flights with different image acquisition axis can eliminate this systematic error even in real-world conditions and that georeferencing without GCPs is, therefore, a feasible alternative to the use of GCPs.

A 12 year old boy was diagnosed with temporal lobe epilepsy (TLE) along with mesial temporal sclerosis based on MRI (magnetic resonance imaging) results. The diagnosis was further confirmed by genetic analysis. He also had minor psychiatric symptoms of obsessive-compulsive disorders and mood swings. After 4 years of treatment with Sodium Valproate no change in symptoms was observed. Genetic testing along with deep phenotyping revealed altered glutamate pathway and metabolism. Post genetic testing the patient was put on a combination of Sodium Valproate and Valproic acid along with supplementation of N-acetylcysteine (NAC), Cyanocobalamin, Pyridoxine and Cholecalciferol. Within three months of this combined therapy the patient experienced complete elimination of seizures and drastic improvement in mood and social behaviour. The case report highlights the importance of precision diagnosis in understanding the underlying perturbed pathways in structural epilepsy like TLE and demonstrates the importance of non-invasive targeted therapy in such cases.

All over the world, development of micro blog and other social platform indicate that Social Media is now the focus and trend of the Internet. Daily life, study and work are influenced by news in Social Medias . Micro blog is new emergent type of media and it spreads information rapidly in the crowd in recent years. Suppose an user searches for specific information about one topic on micro blog. He/she found easily plenty of information related to his/her search in social medias. The problem is to find out the correct information. Normally, multi-document summarization method deals with a collection of documents about one topic for extracting the valuable points and discards useless information. Actually, it needs to extract the topic content by adding topic factors and social patterns. Topic factor is the lexical information related to the topic. Social pattern relates to special interactive mode owned by online social network, such as comment and repost. People has been seen the fake news on mobile/internet during lockdown period. It is of no doubt that anyone with a social media account has seen at least one example of this.Humanity’s greatest challenges are to detect false information. Fake news are collected from 150 persons using social media The aim of the paper is to investigate the truthfulness of the news people share on social media using K-nearest Neighbour (KNN) based Classifier method.

Laser scanning is an effective tool for acquiring geometric attributes of trees and vegetation, which lays a solid foundation for 3-dimensional tree modelling. Existing studies on tree modelling from laser scanning data are vast. Nevertheless, some works don’t ensure sufficient modelling accuracy, while some other works are mainly rule-based and therefore highly depend on user inputs. In this paper, we propose a novel method to accurately and automatically reconstruct tree branches from laser scans. We first extract an initial tree skeleton from the input tree point cloud, then simplify the skeleton through iteratively removing redundant components. A global-optimization approach is performed to fit a sequence of cylinders to approximate the geometry of the tree branches. Experiments on various types of trees from different data sources demonstrate the effectiveness and robustness of our method. The resulted tree models can be further applied in the precise estimation of tree attributes, urban landscape visualization, etc.

In response to the National Institutes of Health (NIH) All of Us Medicine Research Initiative, the Precision Medicine Research (PreMeR) Diversity Consortium was formed by four institutions from the Research Centers in Minority Institutions (RCMI) Translational Research Network (RTRN). This synergistic approach proposed evidence-based, best practices used by experienced researchers to engage, recruit and retain diverse populations in the All of Us initiative. Conceptualization of the proposed approach was aided by social influence theories to better understand how people’s beliefs and opinions should be modified to affect change leading to action [1]. The Social-Ecological Model (SEM), for Health Promotion [2], from Stokols [1] and Community-Based Participatory (CBPR) Models[3],[4] guided proposed engagement, recruitment, and retention strategies contextualized with the individual, interpersonal, organizational, community, and policy spheres of influence. The PreMeR produced a partnership to evaluate and improve the effectiveness of current engagement, recruitment, and retention strategies for minority participation in scientific studies. This approach illustrates the need to incorporate multiple methods of engagement to reach a diverse audience to participate in scientific research. Engagement, recruitment, and retention strategies in community and biomedical research must be viewed as community engaged public health interventions, utilizing the same theoretical principles and approaches.

Τhe concept of remote insect surveillance at large spatial scales for a number of serious insect pests of agricultural and medical importance is introduced in a series of our papers. We augment typical, low-cost plastic traps for many insect pests with the necessary optoelectronic sensors to guard the entrance of the trap in order to detect, time-stamp, GPS tag, and –in relevant cases- identify the species of the incoming insect from their wingbeat. For every important crop pest there are monitoring protocols to be followed in order to decide when to initiate a treatment procedure before a serious infestation occurs. Monitoring protocols are mainly based on specifically designed insect traps. Traditional insect monitoring suffers in that the scope of such monitoring: is curtailed by its cost, requires intensive labor, is time consuming, an expert is often needed for sufficient accuracy and can sometimes raise safety issues for humans. These disadvantages reduce the extent to which manual insect monitoring is applied and therefore its accuracy, which finally results in significant crop loss due to damage caused by pests. With the term ‘surveillance’ we intend to push the monitoring idea to unprecedented levels of information extraction regarding the presence, time-stamping detection events, species identification and population density of targeted insect pests. Insect counts as well as environmental parameters that correlate with insect’s population development are wirelessly transmitted to the central monitoring agency in real time, are visualized and streamed to statistical methods to assist enforcement of security control to insect pests. In this work we emphasize on how the traps can be self-organized in networks that collectively report data at local, regional, country, continental, and global scales using the emerging technology of the Internet of Things (IoT). This research is necessarily interdisciplinary and falls at the intersection of entomology, optoelectronic engineering, data-science and crop science and encompasses the design and implementation of low-cost, low-power technology to help reduce the extent of quantitative and qualitative crop losses by many the most significant agricultural pests. We argue that smart traps communicating through IoT to report in real-time the level of the pest population from the field straight to a human controlled agency can, in the very near future, have a profound impact on the decision making process in crop protection and will be disruptive of existing manual practices. In the present study, three cases are investigated : monitoring Rhynchophorus ferrugineus (Olivier) (Coleoptera: Curculionidae) using a) Picusan and b) Lindgren trap, and c) monitoring various stored grain beetle pests using the pitfall trap.

Generalized relativistic pseudopotentials (GRPP) of atomic cores implying the use of different potentials for atomic electronic shells with different principal quantum numbers give rise to accurate and reliable relativistic electronic structure models of atoms, molecules, clusters, and solids. These models readily incorporate the effects of Breit electron-electron interactions and one-loop quantum electrodynamics effects. Here we report the computational procedure for evaluating one-electron integrals of GRPP over contracted Gaussian functions. This procedure was implemented in a library of routines named LIBGRPP, which can be integrated into existing quantum chemistry software, thus enabling the application of various methods to solve the many-electron problem with GRPPs. Pilot applications to electronic transitions in the ThO and UO2 molecules using the new library and intermediate-Hamiltonian Fock space relativistic coupled cluster method are presented. The results clearly demonstrate that rather economical tiny-core GRPP models can exceed in accuracy relativistic all-electron models defined by Dirac-Coulomb and Dirac-Coulomb-Gaunt Hamiltonians.

Multi-board electronic cases with high density and high power modules are widely used in industrial power supply management. With the improvement of case performance and miniaturization requirements, heat dissipation becomes one of the important factors to be considered in the design process. First,The existing small electronic thermal design methods focus on heat dissipation structure or heat source layout optimization,and ignores on-load test for modeling analysis. Second,The selected power module has on-load power consumption, resulting in relatively low calorific value and the effectiveness of thermal design cannot be verified. Third, The thermal lacks Intelligent monitoring and feedback control mechanism. In order to solve these problems, this paper designs a kind of heat dissipation case with intelligent temperature control based on high-power and high-density power supply array. Based on the extremely miniaturization design principle, we adopt the composite heat dissipation mode based on conduction and supplemented by forced air cooling . The case is made of magnesium and aluminum alloy with a perforated design. Finally, we compare and analyze with the existing cooling design. The results show that the case is smaller in volume, and the cooling performance parameters are slightly better than the existing case. Under the condition of high-density and high-power design, The output power of the whole system is not less than 10kw and the lowest packing-level density is not less than 47w/cm2 with high reliability, portability and practicability. It also provides technical support and prototype support for the standardized design of similar power arrays.

Biliary tract cancers, including intrahepatic, perihilar, and distal cholangiocarcinomas, as well as gallbladder cancer, are a heterogeneous group of cancers with distinct molecular characteristics in each anatomic and pathological subtype. The pathological classification of BTC includes grossly classifiable growth patterns, such as mass-forming, periductal infiltrating, and intraductal growing. The small duct and large duct types of intrahepatic cholangiocarcinoma have been recently introduced in the WHO classification. Typical clinical presentations and various radiological, endoscopic, and molecular modalities for diagnosis are described in detail. To overcome the limitations of traditional tissue acquisition, new diagnostic modalities are being investigated. In fact, the treatment landscape is evolving rapidly owing to the emergence of distinct subgroups harboring unique molecular alterations with corresponding targeted therapies. In addition, we highlight the key points in the diagnostic process in real-world clinical practice for biliary tract cancer.

Myelodysplastic neoplasm (MDS) is a heterogenous clonal disorder of hemopoietic stem cells charac-terized by cytomorphologic dysplasia, ineffective hematopoiesis, peripheral cytopenias and risk of pro-gression to Acute Myeloid Leukemia (AML). Our understanding of this disease has continued to evolve over the last century. More recently prognostication and treatment are determined by cytogenetic and molecular data. Specific genetic abnormalities such as 5q deletion (del 5q), TP53 inactivation and SF3B1 mutation, are increasingly associated with disease phenotype and outcomes, as reflected in the recently updated 5th edition of the World Health Organization Classification of Hematolymphoid Tumors (WHO5) and International Consensus Classification 2022 (ICC 2022) classifications. Treatments are in-creasingly being tailored for patient specific phenotypes, and trials exploring the efficacy of targeted treatments are ongoing in this era of precision medicine.

Neurocutaneous disorders, also known as phakomatoses, are congenital and acquired syndromes resulting in simultaneous neurologic and cutaneous involvement. In several of these conditions, the genetic phenomenon is understood, providing a pivotal role in the development of therapeutic options. This review encompasses the discussion of the genetic and clinical involvement of neurocutaneous disorders and examines clinical management and treatment options. With the current advances in genetics, the role of precision medicine and targeted therapy plays a substantial role in addressing management of these conditions. The interconnectedness between therapeutic options highlights the importance of precision medicine in treating each disorder’s unique molecular pathway. This review provides an extensive synthesis of ongoing and current therapeutics in the management of such clinically unique and challenging conditions.

The current review comprehensively explores the multifaceted landscape of anaplastic lymphoma kinase (ALK) and its pivotal role, specifically within non-small cell lung cancer (NSCLC). It traces the trajectory of ALK's discovery, notably its fusion with nucleolar phosphoprotein (NPM)-1 in anaplastic large cell non-Hodgkin's lymphoma (ALCL) in 1994. It unfolds the subsequent impact of ALK gene alterations across various malignancies, including inflammatory myofibroblastoma (IMT) and NSCLC. The prevalence of intricate ALK rearrangements affecting roughly 3–5% of NSCLC patients prompted the approval of six ALK-tyrosine kinase inhibitors (TKIs) by 2022, revolutionizing the treatment landscape for advanced metastatic ALK+ NSCLC. Second-generation TKIs like alectinib, ceritinib, and brigatinib have notably emerged to combat resistance issues initially associated with crizotinib, the pioneer ALK-TKI approval. Moreover, this review delves into the intersection of ALK and immunotherapy, exploring the potential of immune checkpoint inhibitors in ALK-altered NSCLC tumors. Despite promising preclinical data, challenges encountered in trials evaluating combinations like nivolumab-crizotinib, primarily due to severe hepatic toxicity, underscore the need for cautious exploration of these novel approaches. Additionally, the review delves into innovative avenues such as ALK vaccines and biosensors, shedding light on their promising potential within ALK-driven cancers. This comprehensive analysis encompasses molecular mechanisms, therapeutic strategies, and immune interactions associated with ALK-rearranged NSCLC. Ultimately, the review is a pivotal resource guiding future research and therapeutic interventions in ALK-targeted therapy for NSCLC.

Precision agriculture including camera-guided row detection and hydraulic steering are often used as an alternative because crop damage can be decreased and driving speed can be increased comparable to herbicide applications.The effects of different approaches as uncontrolled (UC), mechanical weed control (MWC), herbicide weed control (HWC) and mechanical + herbicide control (MWC+HWC) on weed density and yield of sugar beet were tested and evaluated in two trials (2021 and 2022) in South Transylvania at the tested intervals BBCH 19 and 31. Weed control efficacy (WCE) depends on the emergence of the weeds and a good timing of weed controls in all the trials and methods, though the highest yield of sugar beet roots was recorded in the treatment MWC+HWC, with an increase up to 12-15% (56.48 t ha-1) yield from HWC (50.22 t ha-1) and a yield increase of more than 35- 40% than MWC (42.34 t ha-1). Our trials show that is possible to increase yield and have less chemical applications with the introduction of the new precision technologies in agriculture included here the sensor-guided mechanical controls.

The advancement of precision medicine in medical care has led behind the conventional symptom-driven treatment process by allowing early risk prediction of disease through improved diagnostics and customization of more effective treatments. It is necessary to scrutinize overall patient data alongside broad factors to observe and differentiate between ill and relatively healthy people to take the most appropriate path toward precision medicine, resulting in an improved vision of biological indicators that can signal health changes. Precision and genomic medicine combined with artificial intelligence have the potential to improve patient healthcare. Patients with less common therapeutic responses or unique healthcare demands are using genomic medicine technologies. AI provides insights through advanced computation and inference, enabling the system to reason and learn while enhancing physician decision-making. Many cell characteristics, including gene up-regulation, proteins binding to nucleic acids, and splicing, can be measured at high throughput and used as training objectives for predictive models. Researchers can create a new era of effective genomic medicine with the improved availability of a broad range of data sets and modern computer techniques such as machine learning. This review article has elucidated the contributions of ML algorithms in precision and genome medicine.

Precision agriculture (PA) is a holistic, sustainable, innovative systems approach that assists farmers in production management. Adopting PA could improve sustainable food security and community economic sustainability. Developing an understanding of PA adoption attributes is needed to assist extension practitioners to promote adoption and better understand the innovation adoption phenomena. A systematic review of literature was conducted to investigate PA adoption. Thirty-three publications were examined, and four themes were found among the reviewed publications. The results were interpreted using Rogers’ diffusion of innovations framework to address the research objectives. Of the reviewed literature, we found relative advantage and compatibility were two dominant attributes to strengthen the adoption of PA, and the complexity attribute was rarely used to promote the adoption of PA. This study shows that change agents do not fully use five attributes of innovation when they promote PA technology to stakeholders to adopt. Thus, we recommend studies from the agricultural extension specialists’ perspectives in the future may determine contributions to motivate farmers’ adoption of PA, in particular related to complexity.

The emergence of three-dimensional human organoids has opened the door for development of patient-derived cancer organoid (PDO) models, which closely recapitulate parental tumor tissue. Mainstays of preclinical cancer modeling include in vitro cell lines and patient-derived xenografts, but these models lack the cellular heterogeneity seen in human tumors. Moreover, xenograft establishment is resource- and time-intensive, rendering these models difficult to use to inform clinical trials and decisions. PDOs, however, can be created efficiently and retain tumor-specific properties such as cellular heterogeneity, cell-cell and cell-stromal interactions, tumor microenvironment, and therapeutic responsiveness. PDO models and drug screening protocols have been described for several solid tumors and, more recently, for gliomas. Since PDOs can be developed in clinically relevant timeframes and share many characteristics of parent tumors, they may enhance the ability to provide precision oncologic care for patients. This review explores the current literature on cancer organoids, highlighting the history of PDO development, organoid models of glioma, and potential clinical applications of PDOs.

Optical sensor data can be used to determine changes in anthocyanins, chlorophyll and soluble solids content (SSC) in apple production. In this study, visible and near-infrared spectra (729 to 975 nm) were transformed to SSC values by advanced multivariate calibration models i.e. partial least square regression (PLSR) in order to test the substitution of destructive chemical analyses through non-destructive optical measurements. Spectral field scans were carried out from 2016 to 2018 on marked ’Braeburn’ apples in Southwest Germany. The study combines an in-depth statistical analyses of longitudinal SSC values with horticultural knowledge to set guidelines for further applied use of SSC predictions in the orchard to gain insights into apple carbohydrate physiology. The PLSR models were investigated with respect to sample size, seasonal variation, laboratory errors and the explanatory power of PLSR models when applied to independent samples. As a result of Monte Carlo simulations, PLSR modelled SSC only depended to a minor extent on the absolute number and accuracy of the wet chemistry laboratory calibration measurements. The comparison between non-destructive SSC determinations in the orchard with standard destructive lab testing at harvest on an independent sample showed mean differences of 0.5 % SSC over all study years. SSC modelling with longitudinal linear mixed-effect (LME) models linked high crop loads to lower SSC values at harvest and higher SSC values for fruit from the top part of a tree.

Despite recent scientific advancements, there is a gap in the use of technology to measure signals, behaviors, and processes of adaptation physiology of farm animals. Sensors present exciting opportunities for sustained, real-time, non-intrusive measurement of farm animal behavioral, mental, and physiological parameters with the integration of nanotechnology and instrumentation. This paper critically reviews the sensing technology and sensor data-based models used to explore biological systems such as animal behavior, energy metabolism, epidemiology, immunity, health, and animal reproduction. The use of sensor technology to assess physiological parameters can provide tremendous benefits and tools to overcome and minimize production losses while making positive contributions to animal welfare. Of course, sensor technology is not free from challenges; these devices are at times highly sensitive and prone to damage from dirt, dust, sunlight, colour, fur, feathers, and environmental forces. Rural farmers unfamiliar with the technologies must be convinced and taught to use sensor-based technologies in farming and livestock management. While there is no doubt that demand will grow for non-invasive sensor-based technologies that require minimum contact with animals and can provide remote access to data, their true success lies in the acceptance of these technologies by the livestock industry.

Background: As part of the Heart Healthy Lenoir Project, we developed a practice level intervention to improve blood pressure control. The goal of this study was: i) determine if single nucleotide polymorphisms (SNPs) that associate with blood pressure variation, identified in large case-control studies, are applicable to blood pressure control in subjects from a rural population; ii) measure the association of these SNPs with subjects’ responsiveness to the hypertension intervention; and iii) identify other SNPs that may help understand patient-specific responses to an intervention. Methods and Results: We used a combination of candidate SNPs and genome-wide analyses to test associations with either baseline systolic blood pressure (SBP) or change in systolic blood pressure one year after the intervention in two genetically defined ancestral groups: African Americans (AA) or Caucasian Americans (CAU). Of the 48 candidate SNPs, 13 SNPs associated with baseline SBP in our study; however, one candidate SNP, rs592582, also associated with a change in SBP after one year. Using our study data, we identified 4 and 15 additional loci that associated with a change in SBP in the AA and CAU groups, respectively. Our analysis of gene-age interactions identified genotypes associated with SBP improvement within different age groups of our populations. Moreover, our integrative analysis identified AQP4-AS1 and PADI2 as genes whose expression levels may contribute to the pleiotropy of complex traits involved in cardiovascular health and blood pressure regulation in response to an intervention targeting hypertension. Conclusions: Identification of SNPs associated with the success of a hypertension treatment intervention suggests that genetic factors in combination with age may contribute to an individual’s success in lowering SBP. If these findings prove to be applicable to other populations, the use of this genetic variation in making patient-specific interventions may help providers with making decisions to improve patient outcomes. Further investigation is required to determine the role of this genetic variance with respect to the management of hypertension such that more precise treatment recommendations may be made in the future as part of personalized medicine.

Super-high (x400) magnification dermoscopy (D400) is a new non-invasive imaging technique that has been shown to add information for the differential diagnosis of melanocytic lesions in a pilot study. Our study aimed to confirm if D400 can add details for the discrimination of clinically atypical nevus and melanoma. This is a retrospective observational, multicentric study enrolling patients who received an x20 (D20) and x400 (D400) magnification dermoscopic examination of pigmented skin lesions. Dermoscopic images were retrospectively evaluated by three observers for the presence/absence of nine D20 and twenty D400 dermoscopic features defined in the previous pilot study. Univariate and multivariate analyses were carried out to find predictors of benign and malignant behaviors. At D20 atypical pigment network, blue-whitish veil, atypical vascular pattern, regression, and homogenous pattern were more frequent in melanoma than in nevi (p&lt;0.001). At D400 melanoma showed more frequently than benign lesions melanocytes with an irregular arrangement and irregular in shape and size (p&lt;0.001). Network with edged papillae was more frequent in benign lesions than melanomas (p&lt;0.001). Our study confirms that D400 can identify melanocytes with an irregular arrangement and irregular in shape and size in melanomas, adding information to the conventional D20 examination.

Chitosan (CTS) is widely used in agriculture as a soil amendment, plant growth regulator and promoter of cold resistance. However, the effects of CTS on strawberry seedlings under the combined stress of high-temperature and high-light are unclear. In this study, Xuelixiang strawberry was used as a test material, and 100 mg·kg-1 CTS solution was sprayed onto the leaves. We measured the chlorophyll content, membrane peroxidation, reactive oxygen species content, antioxidant enzyme content, AsA-GSH cycle activity and other related indicators of strawberry seedling leaves under the combined stress of high-temperature and high-light and found that CTS can increase the contents of antioxidants, increase the contents of osmotic adjustment substances, increase the activity of antioxidant enzymes activity,; remove reactive oxygen species over time, reduce the damage of reactive oxygen species to photosynthetic organs and cell membranes, and improve the photosynthesis efficiency of leaves of strawberry plants under high-temperature and high-light stress, thereby reducing damage to strawberry seedlings caused by high-temperature and high-light.

In-situ injection of steam for heating of the subsurface is an efficient method for the recovery of oil and gas from oil shale where permeability typically evolves with temperature. We reported measurements on Jimusar oil shales(Xinjiang, China) at different temperatures to 600℃ and under recreated in situ triaxial stresses to obtain permeability evolution with temperature and stress. Permeability of tight oil shales evolves with temperature to a threshold temperature and peak temperature. The threshold temperature was subjected to triaxial stresses. For Jimusar oil shale, the threshold temperature ranges from 200℃ to 250℃ at ground stress of buried depth of 500m and from 350℃ to 400℃ at buried depth of 1000m. The peak temperature was almost not subjected to triaxial stress and the range is from 450℃ to 500℃ for all Jimusar samples. Pyrolysis plays an important role in permeability evolution and fundamentally changes permeability tendency and magnitude. At high temperature permeability exhibits a little reduction due to stress effect but still remains a high level due to pyrolysis. The above results show that oil shale mass can change from tight porous media into highly permeable media and oil & gas can easily flow through oil shale stratum.

High-strength wastewaters from a variety of sources, including the food industry, domestic septage and landfill leachate, are often hauled to municipal wastewater treatment plants (WWTPs) for co-treatment. Due to their high organic loadings, these wastewaters can cause process upsets in both the WWTP’s liquid and solids treatment trains and consume organic treatment capacity, leaving less capacity available to service customers in the catchment area. A novel pre-treatment method, the Waste Activated Sludge-High Rate (WASHR) process, is proposed to optimize the co-treatment of high-strength wastewaters. The WASHR process combines the contact stabilization and sequencing batch reactor processes. It utilizes waste activated sludge from the municipal WWTP as its biomass source, allowing rapid start-up. Bench scale treatment trials of winery wastewater confirm the WASHR process can reduce loadings on the downstream WWTP’s liquid treatment and solids treatment trains. A case study approach is used to confirm the economic viability and environmental sustainability of the WASHR process compared to direct co-treatment using life cycle cost analyses and greenhouse gas emissions estimates.

The literature study delves into novel therapeutic strategies in transplantation medicine, highlighting unique approaches that could revolutionize current practices. It emphasizes novel patterns that have the potential to transform the current landscape. Commencing with a thorough examination of the historical environment, it traces crucial advances and changes in transplantation. The focus is on traditional techniques, emphasizing their limitations and challenges. An extensive examination of contemporary transplantation therapies offers valuable insights into the most recent progress in organ, cellular, and tissue transplantation. This analysis examines the immunological obstacles and outlines the current advancements and constraints. The exploration further navigates into novel models and concepts such as immunomodulation, developments in organ preservation techniques, gene editing, biomaterials, scaffold-based solutions, and the integration of precision medicine, artificial intelligence, and machine learning applications. Each section analyzes the potential for change and current progress in various areas, backed by relevant scientific sources up to 2023. The subsequent sections delve into innovative cellular therapies, biotechnological progress, current clinical trials, and case studies demonstrating effective applications. This examination delves into the ethical and regulatory considerations of innovative therapeutic procedures, emphasizing ethical implications, regulatory frameworks, and the importance of balancing innovation with patient welfare. The literature review concludes by offering a forward-looking perspective, emphasizing potential progress, anticipated challenges, and advocating for collaboration and interdisciplinary approaches to overcome limitations in the field of transplantation medicine.

Mutations in epidermal growth factor receptor (EGFR) occur in about 48% of Asian and 19% of Western patients with lung adenocarcinoma (LUAD), leading to its constitutive activation and subsequent uncontrolled cell proliferation. To counteract this, tyrosine kinase inhibitors (TKIs) have been developed, targeting EGFR activity. However, the emergence of metastases and resistance mutations often undermines the durability of the treatment response. Knowledge-based mechanistic models that replicate existing clinical trial outcomes, tailored to specific population characteristics, provide invaluable assistance in designing future clinical trials. These models are particularly effective in identifying optimal responders to specific treatments, thereby enhancing therapeutic efficacy. We have developed physiologically based pharmacokinetic (PBPK) models for gefitinib and osimertinib, representing two distinct generations of EGFR TKIs, to accurately simulate the drugs’ distribution within the primary tumor and metastatic sites following oral administration. These models were integrated with a pathophysiological mechanistic model of EGFR-mutant LUAD, enabling the representation of the effects of both gefitinib and osimertinib on EGFR activation-induced signaling pathways. This comprehensive model outputs detailed evolutions of the primary tumor and each metastatic site, facilitating the evaluation of patient progression in alignment with RECIST guidelines (version 1.1). Notably, the model encapsulates the heterogeneity within the tumor, through the representation of various subclones, each characterized by unique mutation profiles, thereby reflecting differential responses to treatment. Calibration of the model was achieved using publicly available data from the NEJ002 and FLAURA clinical trials. Rigorous visual predictive checks and statistical tests were employed to ensure the proper behavior of the model. The model adeptly replicated the time to progression observed in real clinical trials in EGFR-mutant LUAD patients receiving gefitinib or osimertinib as first-line therapy. In addition, the model was able to reproduce the results from a retrospective study comparing gefitinib and osimertinib, a study that was not used to inform the model. With a consistent virtual population as a reference, the combined model facilitated a comparative analysis of the efficacy of both treatments, thereby underscoring its utility in evaluating therapeutic strategies. The faithful replication of real-world data significantly enhances the credibility of our model, rendering it a vital investigational tool for deriving pertinent insights and informing treatment strategies, particularly in identifying optimal responders to various generations of EGFR TKIs. Following its consecutive prospective validations in the FLAURA2 and MARIPOSA trials, the model is poised to facilitate the generation of synthetic control arms in future clinical trials. This advancement promises a more nuanced analysis of covariate relationships, especially when comparing investigational treatments to established standards of care. Additionally, it potentially reduces the required patient cohort size in such trials, optimizing resource utilization.

The agricultural sector is currently confronting multifaceted challenges such as an increased food demand, a slow adoption of sustainable farming, a need for climate-resilient food systems, resource inequity, and protection of the small-scale farmers’ practices, all issues integral to food security and environmental health. Remote sensing technologies can assist precision agriculture to effectively address these complex problems, by providing farmers with a high-resolution lens. The use of vegetation indices (VIs) is an essential component of remote sensing, which combine the variability of spectral reflectance value (derived from remote sensing data) with the growth stage of crops. Currently a wide array of VIs is available that could be used to provide a classification and an evaluation of the state and health of crops. However precisely this high number leads to difficulties in selecting the best VI and combination of VIs for a specific objective. Without a thorough documentation and analysis of appropriate VIs, users might be confronted with difficulties in using remote sensing data or even with a very low accuracy of the results. Thus, the objective of this review is to conduct a critical analysis of the existing state of the art on the most important features related to the effective use of VIs for the discrimination and monitoring of the most important agricultural crops (wheat, corn, sunflower, soybean, rape, potatoes, and forage crops), grasslands and meadows. This data could be highly useful for all the stakeholders involved in agricultural activities (from farmers, researchers up to institutions dealing with the centralization and monitoring of agricultural crops).

Using nanoparticles (NPs) in drug delivery has exhibited promising therapeutic potential 13 in various cancer types. Nevertheless, several challenges must be addressed, including the 14 formation of the protein corona, reduced targeting efficiency and specificity, potential immune 15 responses, and issues related to NP penetration and distribution within 3-dimensional tissues. 16 To tackle these challenges, we have successfully integrated iron oxide nanoparticles into 17 neuroblastoma-derived extracellular vesicles (EVs) using the parental labeling method. We first de- 18 veloped a tissue-engineered (TE) neuroblastoma model, confirming the viability and proliferation 19 of neuroblastoma cells for at least 12 days, supporting its utility for EV isolation. Importantly, EVs 20 from long-term cultures exhibited no differences compared to short-term cultures. Concurrently, 21 we designed Rhodamine (Rh), Polyacrylic acid (PAA)-functionalized magnetite nanoparticles 22 (Fe3O4@PAA-Rh) with high crystallinity, purity, and superparamagnetic properties (average size: 23 9.2 ± 2.5 nm). We then investigated the internalization of Fe3O4@PAA-Rh nanoparticles within 24 neuroblastoma cells within the TE model. Maximum accumulation was observed overnight while 25 ensuring robust cell viability. However, nanoparticle internalization was low. Taking advantage of 26 the enhanced glucose metabolism exhibited by cancer cells, glucose (Glc)-functionalized nanoparti- 27 cles (Fe3O4@PAA-Rh-Glc) were synthesized, showing superior cell uptake within the 3D model 28 without inducing toxicity. These glucose-modified nanoparticles were selected for parental labeling 29 of the TE models, showing effective NPs encapsulation into EVs. 30 Our research introduces innovative approaches to advance NPs delivery. By partially addressing 31 the challenges associated with 3D systems, optimizing internalization, and enhancing NPs stability 32 and specificity through EV-based carriers. Also, our findings hold the promise of more precise and 33 effective cancer therapies while minimizing potential side effects.

Road traffic transportation has flourished in the process of urbanization by its advantages, but it also produces harmful environmental vibrations. The vibration problem is especially significant for production workshops with precision instruments. A field measurement was conducted to analyze the source characteristics and propagation laws of traffic-induced vibrations. Off the northern side of an urban highway lies a microelectronics workshop. When a large truck passes by, both the vibration responses on the ground and in the workshop considerably increase. Greater vibration is produced in the vertical direction than in the X and Y axes. The predominant frequency band of the vibration response caused by road traffic vehicles is lower than 20 Hz. The vertical vibration responses of the first and second floors in the workshop greatly exceed the VC-C limit because of the high daily traffic flow. Attribute to the excitation of the operation of the manufacturing equipment on the second floor, the vertical vibration level of the second floor is essentially higher than that of the first floor. Therefore, it is impossible to disregard the micro-vibration in the workplace produced by the manufacturing machinery as well as the ex-citement of the road traffic. The measured data can be used to test potential numerical models for forecasting vibrations caused by traffic on roads as well as to guide vibration assessment work throughout the planning and design stages of roads.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of death by cancer worldwide. Mostly diagnosed with locally advanced or metastatic disease, patients lack treatment options. Gene alterations (GAs) are frequently observed in PDAC; some of which are considered for molecular targeted therapies (MTTs), with potential clinical benefits and im-proved outcomes. However, the applicability of molecular profiling (MP) for precision medicine in PDAC remains to be demonstrated. Methods: We conducted a retrospective analysis of all patients, aged ≥18 years with histologi-cally confirmed PDAC, who underwent tumor MP between 2010 and 2020 in our institution as part of personalized medicine trials. The primary study endpoint was overall survival (OS), and (minimal follow-up was 6 months after MP. Results: Of 115 eligible patients, MP was successful in 102 patients (89%). KRAS mutations were the most frequent GAs, mostly G12D. Based on ESCAT classification, actionable GAs were found in 29 patients (28%), involving mainly BRCA1 or BRCA2 (5 [18%]), HER2 (5 [18%]), MTAP (5 [18%]), and FGFR (3 [11%]). Only 12 of these 29 patients (41%, or 10% of the whole population) received MTTs, with a median progression-free survival of 1.6 months. Median OS was 19 months in patients with actionable GAs treated with MTTs (n=12 [11.8%]), 14 months in patients with actionable GAs treated with standard therapies (n=17 [16.7%]), and 17 months in patients without actionable GAs treated with standard therapies (n=73 [71.5%]; p=0.26). The absence of liver metastases was associated with better OS (HR=0.471, p=0.01). The highest OS following MTT was observed in patients with BRCA mutations treated with olaparib. Interpretation: Actionable GAs were found in more than a quarter of patients with advanced PDAC. Overall, targeting actionable GAs with MTTs was not associated with improved OS in this retrospective study with limited patient numbers. However, selected GA/MTT combinations (e.g., BRCA mutations/olaparib) were associated with a better outcome.

Anemia is a well-developed discipline where the concepts of precision medicine have, in part and being studied extensively. This review discusses the treatment of EPO-deficient anemia and resistance in Chronic Kidney Disease (CKD). Traditionally, erythropoietin-stimulating agents (ESA) and iron supplementation have been used to manage anemia in CKD. However, these treatments have potential risks, including cardiovascular and thromboembolic events. Newer treatments have emerged to address these risks, such as slow-release and low-dosage intravenous iron, oral iron, and erythropoietin-iron combination therapy. Another novel approach is using hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI). This review highlights the need for precision medicine targeting genetic components of EPO-deficient anemia in CKD and discusses individual variability of genes such as the erythropoietin gene (EPO), Interleukin-β gene (IL-β), and hypoxia-inducible factor gene (HIF). Pharmacogenomics testing aims to provide targeted therapies and interventions that are tailored to the specific characteristics of an individual, optimizing treatment outcomes and minimizing resistance and adverse effects. The article concludes by suggesting the potential of receptor modification to revolutionize treatment outcome of erythropoietin deficiency anemia through integration of the mentioned approach.

Knowing the spatial variability of factors that influence crop yield is essential to carry out a localized treatment. The present study aimed to map the spatial variability of apparent soil electrical conductivity (ECa) in two cultivation areas, delimit management zones (MZ), characterize the soil density (Sd) at two depths, in each MZ, and assess whether the delimitation of MZ, based on the spatial variability of ECa, was able to identify regions of the productive field with different Sd. Spatial variability of ECa was detected. MZ with the highest mean value of ECa also presented the highest mean values of Sd. The highest Sd values were observed for the 0.1 – 0.2 m layer, regardless of the studied area. Regardless of granulometry, the proposed method was able to detect density differences from ECa. The delimitation of MZ, based on the spatial variability of ECa mapping, was able to differentiate the mean values of Sd between MZ 1 (1.53 g cm-3) and MZ 2 (1.67 g cm-3) in the Area A, in the 0.1 – 0.2 m layer. A statistical difference was observed for the mean values of Sd, in MZ 1, layer 0.1 - 0.2 m, when comparing the two study areas: A (1.53 g cm-3) and B (1.64 g cm-3). We suggest that further studies should be carried out, as the mapping of the spatial variability of the apparent soil electrical conductivity showed potential in the differentiation of soil bulk density at different depths.

Rheumatoid arthritis (RA) is a chronic, systemic, abnormal inflammatory immune response. It is characterized by the involvement of the synovium and multiple organs and the destruction of joints and articular cartilage. Over the past 30 years, several promising novel compounds and antibodies have been developed for the treatment of RA. The introduction of new drugs and precision medicine for all forms of RA raises several issues related to access to novel treatments by patients, optimal regimen selection, cost-effectiveness, prognosis monitoring and outcome surveillance, particularly with regarding to the development of low drug response rates, drug resistance and adverse side effects. Tremendous attention has been given to the identification of optimized drug combinations for the treatment of RA, particularly in early high-risk vulnerable and early individuals. Addressing these issues requires novel therapeutic approaches with new mechanisms and the establishment of accurate guidelines for drug selection, drug recombination, and non-chemical therapeutic efforts. In this study, we reviewed the most exciting recently established or ongoing novel drugs and methods according to the clinical trial database maintained by the United States National Library of Medicine and discussed the trends in RA drug development and challenges in the treatment, providing a reference significant for the accurate treatment of RA and the research direction in the future.

Multiple sclerosis (MS) is a debilitating disease of the brain and spinal cord (central nervous system). In MS, the immune system attacks the protective sheath (myelin) that covers the nerve fibers, causing communication problems between the brain and the rest of the body. Eventually the disease can cause permanent damage or nerve damage. The signs and symptoms of MS are very different and depend on the extent of the nerve damage and which nerves are affected. Some people with severe MS may lose the ability to walk independently or completely, while others may experience a long recovery period without any new symptoms. Most people with MS have a relapsing-remitting illness. They experience periods of new symptoms or recurrences that occur over days or weeks and usually improve somewhat or completely. Following these recurrences, there are periods of recovery that can last for months or even years. In this Project, we used some methods of machine learning in order to evaluate the precision and accuracy of Methods to Predict and classification of Multiple Sclerosis with different stages. In order to calculate accuracy, precision, recall Fscore we used some different method such as Art Fuzzy, SVM, Decision tree to compare the classes two by two. To improve the results we used the method of Adaptive fuzzy optimization. we used two options Genetic algorithm and particle swarm optimization.

Introduction: The current generation of 3D printers are lighter, cheaper, and smaller, making them more accessible to the chairside digital dentist than ever before. 3D printers in general in the industrial and chairside setting can work with various types of materials including, metals, ceramics, and polymers. Evidence presented in many studies show that an ideal material used for dental restorations is characterised by several properties related to durability, cost-effectiveness, and high performance. This review is the second part in a 3D Printing series that looks at the literature on material science and applications for these materials in 3D printing as well as a discussion on the potential further development and future evolution in 3D printing materials. Conclusions: Current materials in 3D printing provide a wide range of possibilities for providing more predictable workflows as well as improving efficiency through less wasteful additive manufacturing in CAD/CAM procedures. Incorporating a 3D printer and a digital workflow into a dental practice is challenging but the wide range of manufacturing options and materials available mean that the dentist should be well prepared to treat patients with a more predictable and cost effective treatment pathway. As 3D printing continues to become a commonplace addition to chair side dental clinics, the evolution of these materials, in particular reinforced PMMA, resin incorporating zirconia and glass reinforced polymers offer increased speed and improved aesthetics that will likely replace subtractive manufacturing milling machines for most procedures.

Introduction: The term 3D printing is commonly used to depict an assembling method whereby the final form of an object is the result of the addition of different layers to build the frame of an object. This procedure is more accurately portrayed as additive manufacturing and is likewise alluded to as fast prototyping. The term 3D printing, in any case, is generally new and has been an active part of current developments in Dentistry. Much publicity encompasses the evolution of 3D printing, which is hailed as an innovation that will perpetually change CAM manufacturing, including in the dental sector. This review is the first part in a 3D Printing series that looks at the history of 3D Printing, the technologies available and reviews the literature relating to the accuracy of these technologies. Conclusions: The recent advancement in digital dentistry to incorporate these tools has modernised dental practices by paving the way for computer-aided design (CAD) technology and rapid prototyping. The use of 3D printing has led to 3D digital models produced with intraoral scanners (IOS), which can be manipulated easily for diagnosis, treatment planning, mockups, and a multitude of other uses. Combining 3D Printing with a 3D intraoral scan eliminates the need for physical storage but makes it to retrieve a 3D models for use within all dental modalities.

Gwosch et al. (2020) and Balzarotti et al. (2017) purport MINFLUX as the next revolutionary fluorescence microscopy technique claiming a spatial resolution in the range of 1-3 nm in fixed and living cells. Though the claim of molecular resolution is attractive, I am concerned whether true 1 nm resolution has been attained. Here, I compare the performance with other super-resolution methods focussing particularly on spatial resolution claims, atypical image rendering, visualisation enhancement, subjective filtering of localizations, detection vs labelling efficiency and the possible limitations when imaging biological samples containing densely labelled structures. I hope the analysis and evaluation parameters presented here are not only useful for future research directions but also microscope users, developers and core facility managers when deciding on an investment for the next 'state-of-the-art' instrument.

Digital twin technology is already improving efficiencies and reducing costs across multiple industries and sectors. As the earliest adopters, space technology and manufacturing sectors have made the most sophisticated gains with automobile and natural resource extraction industries following close behind with recent investments in digital twin technology. The application of digital twins within the livestock farming sector is the next frontier. The possibilities that this technology may fuel are nearly endless as digital twins can be used to improve large-scale precision livestock farming practices, machinery and equipment usage, and the health and well-being of a wide variety of farm animals. Currently, many pioneers of digital twins in livestock farming are already applying sophisticated AI technology to monitor both animals and environment around the clock, which leads to a better understanding of animal behavior and distress, disease control and prevention, and smarter business decisions for the farmer. Mental and emotional states of animals can be monitored using recognition technology that examines facial features such as ear postures and eye white regions. Used with modeling, simulation and augmented reality technologies, digital twins can help farmers build more energy-efficient housing structures, predict heat cycles for breeding, discourage negative behaviors of livestock, and potentially much more. As with all disruptive technological advances, the implementation of digital twin technology will demand a thorough cost and benefit analysis by individual farms. Digital twin application will need to overcome challenges and accept limitations that arise. However, regardless of these issues, the potential of digital twins promises to revolutionize livestock farming in the future.

Adjuvant chemotherapy is currently used in all patients with resected pancreatic cancer who are able to begin treatment within 3 months after surgery. Since the recent publication of the PRODIGE 24 trial results, modified FOLFIRINOX has become the standard-of-care in the non-Asian population with localized pancreatic adenocarcinoma following surgery. Nevertheless, there is still a risk of toxicity, and feasibility may be limited in heavily pre-treated patients. In more frail patients, gemcitabine-based chemotherapy remains a suitable option, for example gemcitabine or 5FU in monotherapy. In Asia, although S1-based chemotherapy is the standard of care it is not readily available outside Asia and data are lacking in non-Asiatic patients. In patients in whom resection is not initially possible, intensified schemes such as FOLFIRINOX or Gemcitabine-Nabpaclitaxel have been confirmed as options to enhance the response rate and resectability, promoting research in adjuvant therapy. In particular, should oncologists prescribe adjuvant treatment after a long sequence of chemotherapy +/- chemoradiotherapy and surgery? Should oncologists consider the response rate, the R0 resection rate alone, or the initial chemotherapy regimen? And finally, should they take into consideration the duration of the entire sequence, or the presence of limited toxicities of induction treatment? The aim of this review is to summarize adjuvant management of resected pancreatic cancer and to raise current and future concerns, especially the need for biomarkers and the best holistic care for patients.

The aim of the instant study was to evaluate relative inline progesterone dynamic changes according to parity and status of reproduction and to estimate the relationship with productivity in dairy cows by inline milk analysis system (IMAS) Herd Navigator. According to a progesterone assay, cows were divided into three periods: postpartum, after insemination, and pregnancy. In the first stage of the postpartum period (0-29 days), the progesterone level in milk was monitored every 6 days. The second stage of the postpartum period (30-65 days) lasted until cows were inseminated. In the third period (0-45 days) after cows were inseminated, progesterone scores were distributed according to whether or not cows became pregnant. The stability of progesterone dynamics was monitored in the last study period (45-90 days). For milk progesterone detection, the fully automated real-time progesterone analyzer Herd Navigator (Lattec I/S. Hillerød. Denmark) was used in combination with a DeLaval milking robot (DeLaval Inc., Tumba, Sweden). The highest progesterone concentration in multiparous cows ranged from 1.08% (11-17 days postpartum) to 34.89% higher than that in cows of the first parity. The lowest progesterone concentrations in the milk of all cows were estimated during the first 5 postpartum days and between 18 and 23 days after calving. Peak milk progesterone concentrations were evaluated in the first stage of the experiment on days 24-29 after calving. In the 30-65-day period after calving, the level of milk progesterone was 2.02-2.08 times higher than that in the 24-29-day postpartum period. After insemination, the level of progesterone in milk increased by 10.77-22.54% compared with the level from cows on days 30-65 after calving. A higher (12.88%) concentration of progesterone in milk was evaluated in multiparous cows compared with that from cows of the first parity. In pregnant cows, milk progesterone within 0-45 days after insemination was 23.88% (in multiparous cows) and 32.54% (in primiparous cows) higher than that in non-pregnant cows. On days 31–35 after insemination, pregnant cows had higher milk progesterone levels, which can predict pregnancy success. According to our study results, we can suggest that an inline progesterone concentration determined by inline milk analysis system Herd Navigator and changes in its dynamics correlate with different reproductive statuses and milk yield of cows. Pregnant cows 11–15 days after insemination have higher milk progesterone levels, what positively, associated with a successful pregnancy.

Previous studies have reported certain sex differences in motor performance precision. The aim of the present study was to analyse sex differences in fine motor precision performance for both hands in different tests conditions. 220 Spanish participants (ages: 12-95) performed fine motor tasks - tracing over the provided models – lines of 40 mm for both hands, two sensory conditions (PV – proprioceptive-visual; P – proprioceptive only) and three movement types (F – frontal, T – transversal and S - Sagittal). Differences in line length (the task focused on precision) were observed through MANOVA analysis for all test conditions, both sexes and different age groups. Sex differences in precision were observed in F and T movement types (statistically significance level and higher Cohens’ d was observed in condition with vision). No any statistically significant differences were observed in both hands and sensory conditions in sagittal type. Sex differences in fine motor precision were more frequently observed in the PV sensory condition in the frontal movement type and less in the sagittal one.

Manufacturing of grinding wheels is continuously adapting to new industrial requirements. New abrasives and new wheel configurations, together with wheel wear control allow for grinding process optimization. However, the wear behavior of the new abrasive materials is not usually studied from a scientific point of view due to the difficulty to control and monitor all the variables affecting the tribochemical wear mechanisms. In this work an original design of pin on disk tribometer is developed in a CNC grinding machine. An Alumina grinding wheel with special characteristics is employed and two types of abrasive are compared: White Fused Alumina (WFA) and Sol-Gel Alumina (SG). The implemented tribometer reaches sliding speeds of between 20 and 30 m/s and real contact pressures up to 190 MPa. The results show that the wear behavior of the abrasive grains is strongly influenced by their crystallographic structure and the tribometer appears to be a very good tool for characterizing the wear mechanisms of grinding wheels, depending on the abrasive grains.

Background Although high-density lipoprotein has cardioprotective effects, the association between serum high-density lipoprotein cholesterol (HDL-C) and hypertension is poorly understood. Objective We investigated whether low and high concentrations of HDL-C are associated with hypertension using a large healthcare dataset. Methods In a community-based cross-sectional study of 1,493,152 Japanese people aged 40–74 years who underwent a health checkup, blood pressures and clinical parameters, including nine HDL-C concentrations (20–110 mg/dL or over) were investigated. Results A crude U-shaped relationship was observed between the nine HDL-C concentrations and blood pressure in males (n = 830,669), while a left-to-right inverted J-shaped relationship was observed in females(n = 662,483). An age-adjusted logistic regression analysis showed J-shaped relationships (left-to-right inversion in females) between HDL-C and odds ratios for hypertension (≥140/90 mmHg), with lower limits of 60–79 mg/dL in males and 90–99 mg/dL in females, which were unchanged after adjusting for smoking, habitual exercise, alcohol consumption, and pharmacotherapy for hypertension, dyslipidemia, and diabetes. However, further adjustment for body mass index and serum triglyceride concentration revealed latent positive linear associations between HDL-C and hypertension, although the association between extremely high HDL-C (≥100 mg/dL) and hypertension was attenuated in non-alcohol drinkers. Conclusion Both low and extremely high HDL-C concentrations are associated with hypertension. The former association may be dependent on excess fat mass, which is often concomitant with low HDL-C, whereas the latter association may be dependent on frequent alcohol consumption.