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.

The demand for animal products is expected to continue to rise, which requires the development of efficient livestock farming systems. Environmental, societal and economic concerns regarding this industry are however accumulating, addressing the large resource demand, pollutants and greenhouse gas emissions and health concerns that the livestock industry is responsible for. Precision livestock farming systems allow the continuous automatic monitoring of various physiological, behavioural and phenotypic parameters of animals in order to increase productivity and animal welfare while controlling and minimizing the environmental impact. There is a high potential for digital farming to be the solution for responsibly and ethically feeding the growing and urbanizing population. However, many problems and concerns are still present in this developing industry and remain relatively unaddressed, starting with the ethical aspects in regard to the animal, including its objectification, human-animal relationships and welfare and ending with the societal implications of this digitalization. Concrete frameworks, inter-disciplinary studies and global legislation need to be put in place in order to ensure the safety and protection of the animals, farmer and society. Here, implications of digital farming for the animals, farmers, society and the planet are critically reviewed with the future outlook of digital farms.

Variable nitrogen(N) rate fertilization based on remote sensing is challenging for cotton production fields, but active crop canopy sensors (ACS) appear as an alternative to make this practical on farm since they can be used at night as well. The crop spatial variability in inherent in crop production in general, and not on-the-go solutions can be used with this type of active sensing technologies. Thus, the purpose of this study was to investigate the potential of two vegetation indices to identify the N requirement variability for cotton plants and to develop prototype algorithms for topdressing nitrogen variable rate on commercial and experimental areas, using the N-sufficiency methodology based on virtual reference. The concept of virtual reference is to use a histogram to characterize the vegetation index of properly fertilized plants without establishing an N-rich plot as a reference strip. The experiment was conducted in strips with four different N rates (0, 45, 90 and 180 kgN ha^-1) during the 2015, 2016, 2017 and 2018 crop seasons in partnership with large cotton producers in Mato Grosso and also in experimental area of Embrapa Agrosilvopastoral. Two algorithms for variable rate nitrogen fertilization for cotton were developed, namely: 1) N recommendation algorithm for cotton in commercial production system: N rate (kg.N ha^-1) = -234.79 ISN² + 49,879 ISN + 195.15; R² = 0.97; and 2) for cotton grown in experimental area: N dose (kgN ha^-1) = -174.73 ISN² - 107.21 ISN + 306.78; R² = 0.94.

Cotton is the most ubiquitous and profitable fiber with diverse industrial and domestic applications. Grown in over 100 countries, it has a global market value of about $40 billion and employs over 350 million people from fields to textile mills, contributing about 7% of total labor-force recruitment in developing economies. Cotton has an indeterminate growth habit and an extensive tap root system affected by soil physicochemical and environmental conditions. There is a consensus among experts that conventional cotton cultivation still has a long way to attain sustainability, which is essential if cotton will maintain its competitive edge over other natural and synthetic fibers like hemp, polyesters, and rayon. Despite several efforts already committed to growing cotton sustainably, sustainability has eluded cotton cultivation globally because of the intense farm inputs (freshwater, pesticides, and heavy-duty equipment) needs, especially in developing economies. Some of the technological advancements towards achieving the goal of sustainable cotton cultivation include the development of new varieties, improved irrigation and mulching and precision agriculture techniques, application of remote sensing and Unmanned Aerial Systems (UAS) combined with image processing, and the introduction of autonomous and multi-purpose robotic platforms for growing and harvesting cotton. This review attempts to evaluate the successes already achieved by stakeholders in moving cotton towards sustainable production and identify areas where efforts are still needed to reach sustainable production and improved profitability goals for cotton with projections for future research directions.

Precision farming is transforming how antibiotics get used on farms. It fights the overuse that creates superbugs and harms nature. Farmers now have high-tech tools to use antibiotics ultra-precisely. Drones, AI, and advanced watering equipment help them pinpoint only sick plants and animals needing treatment. This shields crops while avoiding environmental damage. More careful antibiotic use makes livestock healthier and boosts harvests too. And it prevents resistant germs, where antibiotics stop working altogether. The approach helps farms in multiple ways, using fewer resources for even better results. There are some growing pains, like high costs for small farms. And questions around data privacy also cause concern. But overcoming these hurdles could help precision farming spread far and wide. This technology promises safer, greener, and more productive agriculture. Targeted use of antibiotics protects both crops and people from drug-proof germs. And nature benefits when less medicine spreads into soil and water. The future looks bright for farming with precision.

Infrared thermography is a contactless imaging technique, useful to measure surface temperature at distance which has been widely applied in animal production. The possible applications within the pig husbandry include sow heat detection, reduction of the incidence of neonatal mortality, recognition of febrile state caused by pathogens, study of metabolic efficiency, evaluation of stress caused by heat, by constraints, or by aggressive interaction and meat quality prediction. Even if this technique could be easily influenced by environmental factors, the continuous improvement in the procedures and the decrease in the cost of the equipment will allow in the next future new and more applications in swine farming.

The emergence of precision and digital livestock farming presents an opportunity for sustainable animal farming practices that enhance animal welfare and health. However, this transformation of modern animal farming through digital technology has several implications for the technological, social, economic, and environmental aspects of farming. It is crucial to analyze the ethical considerations associated with the digitalization of modern animal farming, particularly in the context of human-animal relationships and potential objectification. This analysis can help develop frameworks for improving animal welfare and promoting sustainability in animal farming.One of the primary ethical concerns of digital livestock farming is the potential for a digital divide between farmers who have access to advanced technologies and those who do not. This could lead to a disparity in animal welfare and health outcomes for different groups of animals. Additionally, the use of artificial intelligence in digital livestock farming may lead to a loss of personal connection between farmers and animals, which could impact the animal's well-being. Another ethical concern of digital livestock farming is the potential for objectification of animals as mere data points. The use of sensors and other monitoring technologies can provide valuable data on animal health and behavior, but it is important to remember that animals are sentient beings with complex emotional and social needs. The use of digital technologies should not lead to neglect of animal welfare or a lack of human responsibility towards animals.Furthermore, social context becomes essential while integrating technologies in the livestock farming to overcome ethics. By considering the cultural and societal norms of different communities, we can ensure that the use of digital technologies does not undermine these values. To address these ethical challenges, the development of standards and codes of conduct for the adoption and implementation of digital livestock farming tools and platforms can help ensure that animal welfare and sustainability are prioritized. This can help alleviate the privacy concerns of stakeholders and improve sustainability in animal farming practices. Additionally, the use of virtual and augmented reality technologies can provide a way to enhance human-animal interactions and provide more personalized care to animals, further promoting animal welfare.

The metaverse, a virtual world comprising a collective virtual shared space where users interact with one another through avatars and computer-generated objects, aims to closely mimic our real world by integrating elements of Artificial Intelligence (AI), immersive reality, advanced connectivity, and Web3. As metaverse technologies gain momentum across multiple sectors, including animal farming, their potential for addressing complex challenges such as climate change and sustainability in precision food production systems becomes increasingly apparent. However, it is crucial to consider the ethical implications and the role of sensor data and livestock behavior analysis in developing metaverse technologies for modern animal farming, given the sensitive and controversial nature of animal welfare. Failure to address these ethical considerations and harness the power of sensor data and behavior analysis could lead to a lack of credibility and insensitivity towards adopting metaverse technologies in the animal farming sector. It is essential to ensure that the development of metaverse technologies does not prioritize technology over animal welfare, ethics, socio-economic implications, and the potential for data-driven insights. Addressing diversity and equity in the context of animal farming and the metaverse is crucial to avoid perpetuating existing inequalities during the implementation of metaverse technologies. This groundbreaking paper ventures into unexplored territory, shedding light on the untapped potential of the metaverse for modern animal farming. While research on this topic is still in its infancy, we embark on a journey of visionary speculation, presenting a compelling technology forecast that envisions the extraordinary possibilities awaiting us in the future. By delving into the metaverse's transformative capabilities, we provide a glimpse into a world where animal farming transcends its traditional limitations and embraces a new era of efficiency, sustainability, and ethical practices.

This paper pioneers a novel exploration of environmental impacts in livestock farming, with a focus on pig farming's intersection with climate change and sustainability. It emphasizes the transformative potential of data-driven Artificial Intelligence (AI) methodologies, specifically the Internet of Things (IoT) and multimodal data analysis, in promoting equitable and sustainable food systems. The study observes five pigs, aged 86 to 108 days, using a tripartite sensor that records heart rate, respiration rate, and accelerometer data. The unique experimental design alternates between periods of isolation during feeding and subsequent pairing, enabling the investigation of stress-induced changes. Key inquiries include discerning patterns in heart rate data during isolation versus paired settings, fluctuations in respiration rates, and behavioral shifts induced by isolation or pairing. The study also explores potential detection of gait abnormalities, correlations between pigs' age and their gait or activity patterns, and the evolution of pigs' walking abilities with age. The paper scrutinizes accelerometer data to detect activity changes when pigs are paired, potentially indicating increased stress or aggression. It also examines the adaptation of pigs to alternating isolation and pairing over time, and how their heart rate, respiration rate, and activity data reflect this process. The study considers other significant variables, such as time of day and isolation duration, affecting the pigs' physiological parameters. Sensor data is further utilized to identify behavioral patterns during periods of feeding, isolation, or pairing. In conclusion, this study harnesses IoT and multimodal data analysis in a groundbreaking approach to pig welfare research. It underscores the compelling potential of technology to inform about overall pig welfare, particularly stress levels and gait quality, and the power of data-driven insights in fostering equitable, healthy, and environmentally conscious livestock production systems.

Artificial Intelligence (AI) is increasingly becoming integral to medical practice, potentially enhancing outcomes in thoracic surgery. AI-driven models have shown significant accuracy in diagnosing non-small cell lung cancer (NSCLC), predicting lymph node metastasis, and aiding in the efficient extraction of electronic medical records (EMR) data. Moreover, AI applications in robotic-assisted thoracic surgery (RATS) and perioperative management reveal potential in improving surgical precision, patient safety, and overall care efficiency. Despite these advancements, challenges such as data privacy, biases, and ethical concerns remain. This manuscript explores AI applications, particularly machine learning (ML) and natural language processing (NLP), in thoracic surgery, emphasizing their role in diagnosis and peri-operative management. It also provides a comprehensive overview of the current state, benefits, and limitations of AI in thoracic surgery, highlighting future directions in the field.

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.

Despite the known benefits of precision agriculture, the adoption is challenging due to the cost of investment and the farm sizes. Therefore, profitability is an important aspect to consider. This study aimed to evaluate the net returns, profitability, and investment efficiencies of PA by different economic farm sizes. The study was based on data retrieved from FADN and Eurostat. The study examined four countries (Poland, Germany, France, and Romania) under field crop farming using an investment cost of €35 941 - €71 883, and a 20% and 15% reduction in the cost of crop protection and fertilizer usage respectively without compromising productivity. There is a positive relationship between the adoption of PA and farm returns for larger-scale farms. The result of the profitability and analysis of investment efficiency using NPV showed a positive value for economic farm sizes of €100 000 and above. Hence, it is not economically advisable that all farmers use PA technologies with the hope that they will be profitable but with public support (subsidies) more farms will be able to use PA and be profitable. Also, an opportunity to meet the goal of the European Union Green Deal of minimizing emissions that cause climate change.

Beans are the most widely used protein source in the world and their productivity is directly linked to nitrogen (N). The short crop cycle imposes the need for fast methodologies for N quantification. In this work, we evaluated the performance of four machine learning algorithms in nitrogen prediction using NIR spectroscopy. Increasing doses of nitrogen were applied to the plants and leaf reflectance was collected. Weka software was used to test the algorithms. The selection of the most effective spectral zones was made with the VIP. Considering predictions with the whole NIR, the best results were achieved with RF (R2 = 0,84 and RMSE = 2,69 g kg-1) and KNN (R2 = 0,77 and RMSE = 3,86 g kg-1). The intervals of 700-740 nm and 983-995 nm were considered the most important for the study of N. More efficient predictions were verified when only spectral regions screened by VIP were included, increasing the accuracy of the RF, KNN and M5 models by 6%, 4% and 8%, respectively. The efficiency of N prediction based on NIR reflectance combined with machine learning was verified. This approach can optimize the management of nitrogen fertilization, serving as an important tool in precision agriculture.

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.

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.

Murine xenograft models are valuable and increasingly used preclinical tools in cancer research to understand disease pathogenesis and guide treatment options. The aim of this narrative review is to summarize the studies that employed mouse xenograft models, using cell-lines, patient-derived tumors, or organoids, in endometrial cancer (EC) research, detailing their methodology and main findings. We identified 27 articles reporting on heterotopic EC xenografts, including subcutaneous, subrenal capsule, intraperitoneal, and retro-orbital models, and 18 articles using orthotopic xenografts. Subcutaneous xenografts generated using either cell-lines or patient tumors have been widely used, however, their low engraftment rates and the inability to recapitulate main clinical features such as metastases limit their translational value. Subrenal capsule models showed improved engraftment rates compared to subcutaneous models, but tumors exhibited slower and constrained tumor growth. Orthotopic models are technically more challenging to generate and monitor, but tumor growth occurs in a relevant microenvironment and EC ortho-xenografts exhibit high engraftment rates and metastases to clinically relevant sites. Cell-line based xenograft (CDXs) models are attractive tools because they are convenient, easy to use, and amenable to genetic modifications, making them suitable for proof-of-concept approaches and large-scale studies. EC xenografts developed from patient tumors (PDTXs) are more labor/cost intensive for their establishment but can capture the genetic and molecular heterogeneity within and across histologic subtypes and can inform on personalized patient treatment. EC organoid-based xenograft (PDOXs) models combine advantages of both CDXs and PDTXs since are more time and cost effective, maintain faithfully tumor characteristics and therapeutic responses, and can be genetically modified. Despite substantial progress in EC management, there are still several unmet needs. Efficient targeted treatments are currently indicated only for a small subgroup of patients, while women with recurrent or advanced stage EC have very few therapeutic options and their prognosis remains unfavorable. Novel (targeted) drugs, combinational regimens and tools to predict the real drug response in patients are urgently needed. Xenograft models are expected to inform on disease mechanisms and to help identify novel therapeutic options and the suitable target patients.

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.

This study aimed to analyze the productive behavior of the maize crop, cultivated at different population densities, in management zones (MZ) delimited based on mapping the spatial variability of the soil apparent electrical conductivity (ECa). The soil ECa was measured and two MZs were subsequently delimited, one with low and the other with high ECa. In each MZ, four maize sowing densities were tested: 60,000 (D1); 80,000 (D2); 100,000 (D3) and 140,000 (D4) seeds ha-1. Ear length, number of grains per ear, number of grains per row, number of rows per ear, thousand-grain weight, and yield were evaluated. The increase in sowing density in the high ECa MZ linearly reduced the values of ear diameter, number of rows per ear, number of grains per ear and thousand-grain weight. Sowing density D3, when implemented in the low ECa MZ, showed higher values for the ear length, ear diameter, number of grains per row, number of grains per ear, and thousand-grain weight. Sowing density D2 was the one with the highest yield, regardless of the MZ where it was implemented (5,628.48 kg ha-1 in the high ECa management zone and 4,463.63 kg ha-1 in the low ECa).

Background/Objectives: The global burden of colorectal cancer (CRC) is projected to increase by 2040, highlighting the need for prevention strategies, early detection and adequate follow. The aim of this study was to provide an overview of the progress in personalized medicine of CRC in Serbia, with results and insights from the Institute for Oncology and Radiology of Serbia (IORS), and to propose guidance for tackling observed challenges in the future. Methods: Epidemiological data was derived from official global and national cancer registries and IORS electronic medical records. Germline genetic testing for Lynch syndrome was performed by Next Generation Sequencing. RAS and BRAF mutation analyses were performed using qPCR diagnostic kits. Results: Epidemiology and risk factors, prevention and early detection programs, as well as treatment options and scientific advances have been described in detail. Out of 103 patients who underwent germline testing for Lynch syndrome, 19 (18.4%) had a pathogenic or likely pathogenic mutation in one of the MMR genes, and 8 (7.8%) in other CRC-associated genes (APC, CHEK2, MUTYH). Of 6369 tested patients, 50.43% had a mutation in KRAS or NRAS genes, while 9.54% had the V600 mutation in the BRAF gene. Conclusions: Although significant improvements in CRC management have occurred globally in recent years, the high incidence of young-onset CRC and the growing elderly population due to a rise in life expectancy require a strategic approach leading to population-based systemic solutions, especially important for countries with limited health care resources as Serbia.

Automating pruning tasks entails overcoming several challenges, encompassing not only robotic manipulation but also environment perception and detection. To achieve efficient pruning, robotic systems must accurately identify the correct cutting points. A possible method to define these points is to choose the cutting location based on the number of nodes present on the targeted cane. For this purpose, in grapevine pruning, it is required to correctly identify the nodes present on the primary canes of the grapevines. In this paper, a novel method of node detection in grapevines is proposed with four distinct state-of-the-art versions of the YOLO detection model: YOLOv7, YOLOv8, YOLOv9 and YOLOv10. These models were trained on a public dataset with images containing artificial backgrounds and afterwards validated on different cultivars of grapevines from two distinct Portuguese viticulture regions with cluttered backgrounds. This allowed to evaluate the robustness of the algorithms on the detection of nodes in diverse environments, compare the performance of the YOLO models used, as well as create a publicly available dataset of grapevines obtained in Portuguese vineyards for node detection. Overall, all used models were capable of achieving correct node detection on images of grapevines from the three distinct datasets. Considering the trade-off between accuracy and inference speed, the YOLOv7 model demonstrated to be the most robust in detecting nodes in 2D images of grapevines, achieving F1-Score values between 70 % and 86.5 % with inference times of around 89 ms for an input size of 1280×1280 px. Considering these results, this work contributes with an efficient approach for real-time node detection for further implementation on an autonomous robotic pruning system.

Medullary thyroid carcinoma (MTC) is a rare yet aggressive form of thyroid cancer, comprising a disproportionate share of thyroid cancer-related mortalities despite its low prevalence. MTC differs from other differentiated thyroid malignancies due to its heterogeneous nature, presenting complexities in both hereditary and sporadic cases. Traditional management guidelines, designed primarily for papillary thyroid carcinoma (PTC), fall short in providing the individualized care required for MTC patients. In recent years, the sheer volume of data generated from clinical evaluations, radiological imaging, pathological assessments, genetic mutations, and immunological profiles has made it humanly impossible for clinicians to simultaneously analyze and integrate these diverse data streams effectively. This data deluge necessitates the adoption of advanced technologies to assist in decision-making processes. Holomics, an integrated approach that combines various omics technologies, along with artificial intelligence (AI), emerges as a powerful solution to address these challenges. AI-driven precision oncology can significantly enhance the diagnostic work-up, staging, risk stratification, management, and follow-up care of MTC patients by processing vast amounts of complex data quickly and accurately. AI algorithms can identify patterns and correlations that may not be apparent to human clinicians, thereby improving the precision of personalized treatment plans. Moreover, the implementation of AI in MTC management enables the collation and synthesis of clinical experiences from across the globe, facilitating a more comprehensive understanding of the disease and its treatment outcomes. This global approach aligns with the United Nations Sustainable Development Goal 3, which aims to ensure healthy lives and promote well-being for all at all ages. By leveraging AI and holomics, we can strive towards making personalized healthcare accessible to every individual, regardless of their economic status, thereby improving overall survival rates and quality of life for MTC patients worldwide. In conclusion, the integration of holomics and AI in the management of medullary thyroid carcinoma represents a significant advancement in precision oncology. This innovative approach not only addresses the complexities of a rare and aggressive disease but also paves the way for global collaboration and equitable healthcare solutions, ultimately transforming the landscape of MTC treatment and care.

Aims. Bone metastases have an incidence of up to 75% in metastatic breast cancer, thanks to the evolution of imaging we can identify them in the oligometastatic phase. With the introduction of target therapies and increasingly effective conjugated antibodies, it is increasingly common to treat patients with radiotherapy although asymptomatic (if single or ≤5 bone lesions). Volumes and doses in this setting do not yet have a clear guidelines. In this study, the aim is to administer to the macroscopically evident disease an ablative dose that favors the local control of disease. Aim of this retrospective analysis is to evaluate the outcome of pts receiving SIB for treatment of bone metastases. Material and Methods. A retrospective analysis including mBC patients (pts) undergone RT on bone metastases was conducted for pts treated between January 2014 and January 2022. Primary endpoint was freedom from local progression (FFLP). Rate of disease progression after radiotherapy (DP-AR) and overall survival (OS) were secondary endpoints. Subgroup analysis (age, immunophenotype, line of therapy) were performed. Results. Among 954 mBC who underwent radiotherapy for metastases, 85 pts underwent SIB-IMRT with a boost on macroscopic lesion of 8-6 Gy in 5 fr. Mean follow up was 41 months (6-61.5 m). Nineteen pts had single bone metastase (22.4%), 20 pts were oligometastatic (23,5%), 46 pts were plurimetastatic (54,1%). FFLP was 17 months (95% CI 3.2-61.5 m). Only 6 pts (7%) had local relapse on SIB-IMRT site during follow up. DP-AR was 13,2 m (95% CI 3.1-56.9 m). OS was 82,7 m (95% CI 10.6-343 m). Local-relapse was not associated with age, immunophenotype or sistemic line ongoing. Among secondary outcomes, DP-AR resulted associated to immunophenotype (p 0.002). DP-AR and OS were not significantly associated with local relapse (respectively p 0.148 and p 0.4). Conclusions. Pts with breast tumor can be treated with SIB-IMRT on bone metastases with a 93% of local control at 17 months from radiotherapy. Further data are needed to individuate pts who can benefit of dose-escalation and also sinergic effect with systemic therapies to possibly increase DP-AR.

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.

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.

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.

After the launch of a high-resolution remote sensing satellite, representative spatial quality estimators (RER, FWHM, MTF50, MTFA) are measured from images taken of ground Edge targets. In this work, the best spatial quality estimator is proposed by quantitatively comparing and analyzing the precision between Relative Edge Response (RER), Full Width at Half Maximum (FWHM), MTF value at Nyquist frequency (MTF50), and MTF Area between 0 and Nyquist frequency (MTFA). While the basic method for the measurement of spatial quality estimators on Edge targets is already well established, this work summarizes and explains the uncertain factors and problems in the measurement procedure that affect the accuracy and precision of spatial quality estimators. It also considers how to improve the precision of spatial quality estimators during the measurement procedure. The contents and results of this work were discussed by various satellite development organizations in the Geo-Spatial Working Group within CEOS WGCV IVOS from 2012 to 2019, and the Edge target Spatial quality Measurement Python code (ESMP) was developed in 2019 to reflect the findings of this workshop. Using 483 Edge targets from worldwide images taken by KOMPSAT-3A, which has been in operation since 2017, the results obtained via ESMP show that the precision of RER, FWHM, and MTFA are approximately three to four times higher than that of MTF50 when comparing the Coefficient of Variance (CV) statistics.

The growing use of drones in precision agriculture highlights the need for enhanced operational efficiency. Despite the ability of computer vision based on deep learning has made remarkable progress in the past ten years, when it comes to segmentation task on UAVs, there is always a conflict between the demand of high precision and low inference latency. Due to such a dilemma, we propose the IRB-YOLO, an efficiency model based on Inverted Residual Block, devoting to provide constructive strategies in real-time detection tasks of UAV camera. The working details of this paper are as follows: (1) This paper innovates with a IR-Block(Inverted Residual Block), integrated into a refined YOLOv8-seg structure to create IRB-YOLO. This model specializes in pixel-level classification of UAV-acquired RGB images, facilitating the creation of exact maps to guide agricultural strategies. (2)When it comes to the experiments on a Vatica dataset with any other light-weight segmentation model, IRB-YOLO achieve at least a 3.3% increase in mAP. Further validation using a diverse species dataset confirms its robust generalization. (3)Without overloading the complex attention mechanism and deeper and deeper network, a stem that incorporates efficient feature extraction components, inverted residual block, can still possess outstanding modeling capabilities. IRB-YOLO builds a bridge between academic research and edge deployment of drones, making it applicable in real-world scenarios.

Real-Time Kinematic (RTK) is currently the most widely used method for positioning using Global Navigation Satellite Systems (GNSS) due to its accuracy, efficiency and ease of use. In forestry, position is a critical factor for numerous applications, with GNSS nowadays the preferred solution for obtaining such data. However, the decreased performance of GNSS observations in challenging environments, such as under the forest canopy, must be considered. This paper analyzes the performance of a survey-grade GNSS receiver under coniferous/deciduous tree cover, with short observation times of 30 seconds and corrections received in the field from a Continuously Operating Reference Station (CORS) of the national RTK network in Romania. 84 test points were determined, randomly distributed under the canopy, with reference data collected by topographical surveys using total station equipment. Relatively good accuracies were obtained, especially for horizontal position (RMSEs of 1.47 – 2.07 meters). The variation of GNSS performance under the different forest compositions was found to be statistically significant, while GNSS-specific factors such as DOP values only influenced the precision and not the accuracy of observations. We established that this methodology offers sufficient accuracy, application-dependent, even if the majority of GNSS solutions were code-based, rather than carrier phase-based, due to strong interference from the vegetation.

The autonomous displacement and displacement measurement functions of the maglev ruler are performed by the mover core. The stability of the four magnetic field in air gaps and the levitation position of the maglev ruler is one of the key factors for the stability of the thrust force on the power core, and it is also one of the key factors for ensuring the precision of the maglev ruler. There is cross-coupling between the two ends of the mover core of the maglev ruler, resulting in a strongly coupled, nonlinear, multi-input and multi-output system for the levitating system of the maglev ruler. This paper establishes a mathematical model for the levitating system of the maglev ruler, and designs a levitating control system for the maglev ruler based on ADRC control algorithm to achieve decoupling and disturbance suppression. Through simulation analysis and experimental testing of the levitating system with starting and disturbance, it is proved that the levitating control system of the maglev ruler has good dynamic characteristics, static characteristics, and robustness.

Constructing a globally consistent high-precision map is essential for the application of mobile robots. Existing optimization-based mapping methods typically constrain robot states in pose space during the graph optimization process, without directly optimizing the structure of the scene, thereby causing the map to be inconsistent. To address the above issues, this paper presents a three-dimensional (3D) LiDAR mapping framework (i.e., BA-CLM) based on LiDAR bundle adjustment (LBA) cost factors. We propose a multivariate LBA cost factor, which is built from a multi-resolution voxel map, to uniformly constrain the robot poses within a submap. The framework proposed in this paper applies the LBA cost factors for both local and global map optimization. Experimental results on several public 3D LiDAR datasets and a self-collected 32-line LiDAR dataset demonstrated that the proposed method achieves accurate trajectory estimation and consistent mapping.

Vitronectin is a glycoprotein, present in plasma and extracellular matrix, implicated in cell migration. The high amount of vitronectin found in neuroblastoma biopsies was associated with poor prognosis. However, there are almost no studies of vitronectin levels in neuroblastoma cell culture media nor in plasma of neuroblastoma patients. Vitronectin concentration in culture media of four neuroblastoma cell lines grown in monolayer and in 3D-models, and in plasma of 114 neuroblastoma patients, was quantified using ELISA. Three of the neuroblastoma cell lines secreted vitronectin to culture media when cultured in monolayer and 3D-models. Vitronectin release was higher by neuroblastoma cells cultured in 3D-models than in monolayer, and was still great when cells grown in 3D-scaffolds with cross-linked vitronectin. Vitronectin secretion occurred independently of cell numbers in cultures. Its concentration in plasma of neuroblastoma patients ranged between 52.4 and 870µg/mL (median, 218µg/mL). A ROC curve was used to establish a cutoff of 361µg/mL, above which patients over 18-months-old had worse prognosis (p=0.0018). Vitronectin could be considered a new plasma prognostic biomarker in neuroblastoma, and warrants confirmation in collaborative studies. Drugs inhibiting vitronectin interaction with cells and/or extracellular matrix could represent a significant improvement in survival for neuroblastoma patients.

In recent years, bioengineered and biotechnological products have gained tremendous attention to identify unique biologic features associated with oncology. To overwhelm the complexity of tumor personalized medicines (PM) or vaccines could be a promising way-out to be considered. Cancer is a heterogeneous disease. This characteristic variability of cancer provides itself to the emergent era of PM i.e., precision oncology. The prime objective of PM is merely to deliver the right treatment to the right patient at the right time. For instance, imatinib was effectively targeted chronic myeloid leukemia. To date, attainment in using PM approaches to cancer treatment have been mixed. The next-generation sequencing (NGS), and the use of several biomarkers (e.g., HER2, BRAF, ALK, etc.), to drive precise cancer treatment through a timely and cost-effective manner. In current review, author summarizes the advancement in the field of PM such as CRISPR-Cas9, NGS, pharmacogenomics, and the benefits of machine learning techniques. The precise communication between healthcare professionals, regulatory bodies, and patients is essential to translate advances in PM into immense benefits for patients with cancer globally.

Biological nitrogen fixation (BNF) by symbiotic bacteria plays a vital role in sustainable agriculture. However, current quantification methods are often expensive and impractical. This study explores the potential of Raman spectroscopy, a non-invasive technique, for rapid assessment of BNF activity in soybeans. Raman spectra were obtained from soybean plants grown with and without rhizobia bacteria to identify spectral signatures associated with BNF. δN15 isotope ratio mass spectrometry (IRMS) was used to determine actual BNF percentages. Partial least squares regression (PLSR) was employed to develop a model for BNF quantification based on Raman spectra. The model explained 80% of the variation in BNF activity. To enhance the model's specificity for BNF detection regardless of nitrogen availability, a subsequent elastic net (Enet) regularization strategy was implemented. This approach provided insights into key wavenumbers and biochemicals associated with BNF in soybeans.

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.

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.

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.

Thoracic ultrasonography (TUS) has emerged as a critical tool in the diagnosis and management of respiratory diseases in cattle, particularly bovine respiratory disease (BRD), which is one of the most economically significant health issues in feedyard operations. The objective of this review is to explore TUS in veterinary medicine including the historical development, methodologies, and clinical applications for diagnosing and prognosing respiratory diseases. The review also emphasizes the importance of operator training, noting that even novice operators can achieve diagnostic consistency with proper instruction. Ultrasound was introduced in the mid-20th century for back-fat thickness measurements, TUS has evolved to offer a non-invasive, real-time imaging modality that allows for the detection of lung and pleural abnormalities such as consolidations, pleural effusions, and B-lines. These features are vital indicators of respiratory disease, and their early identification through TUS can significantly improve clinical outcomes. Compared to traditional diagnostic methods like auscultation or radiography, TUS provides superior accuracy in detecting both subclinical and advanced respiratory conditions, particularly in high-risk populations. Furthermore, TUS has demonstrated strong prognostic value, with studies showing that the extent of lung consolidation correlates with higher relapse risk, reduced growth performance, and increased mortality.

The clinical outcome for children diagnosed with acute lymphoblastic leukemia is a testimony to the success of modern medicine. Over the past several decades, survival has climbed from ∼ 10% to &gt; 90% for certain subgroups. Yet, the outcome for those with relapsed disease is often poor and survivors struggle with a multitude of healthcare issues, some of which are lifelong. In recent years, the advent of widespread sequencing of tumors has made available previously unrecognized subtypes of leukemia patients who have the potential to benefit from the addition of targeted therapies. Indeed, the promise of precision medicine encompassing a person's environment, genetics and lifestyle is likely to have profound impact on further tailoring therapies that are likely to improve outcomes, diminish toxicity and ultimately pave the pathway for a healthier population.

Plant diseases not only cause economic losses, but they also pose a health risk. In this regard, aflatoxins are linked to the development of some type of liver cancer, especially the hepatocellular carcinoma. Aflatoxins are usually produced by the fungi Aspergillus flavus and Parsiticus in figs, and their identification is usually carried out using invasive and complex methods or by visual inspection at an advanced stage. Given that Spain is one of the main producers of figs and Extremadura is the leading region in the country, it is necessary to explore alternative ways of detecting the presence of aflatoxins in figs and preventing them from entering the food chain. The aim of this research is to address the early detection of Aspergillus flavus fungus using non-invasive techniques with the aid of hyperspectral imaging and the application of artificial intelligence techniques, in particular deep learning. The images were taken after inoculation of the microtoxin using 3 different concentrations, related to three different classes and healthy figs (healthy controls). The analysis of the hyperspectral images was performed at the pixel level. Firstly, a full connected neural network was used to analyse the spectral signature associated with each pixel; second, the wavelet transform was applied to each spectral signature. The resulting images are fed to a convolutional neural network. The hyperparameters of the proposed models were adjusted based on the parameter tuning process also performed. The results are promising, with 83% accuracy, 82.75% recall and 83.25% F1-measure for the single neural network, and 77.25% accuracy, recall and F1 for the convolution neural network.

The agricultural industry prioritizes crop protection, particularly against threats like pink bollworm infestations in cotton crops. This paper presents a comprehensive solution using the Robot Operating System (ROS) to deploy an autonomous robot for detecting pink bollworm infestations and tracking red illnesses. Drones collect multispectral photos of cotton fields, aiding path planning via Normalized Difference Vegetation Index (NDVI) computations. A bespoke dataset of RGB and multispectral images trained a YOLOv8 model for object detection, achieving a mean Average Precision (mAP) of 67.1%, Precision of 67.9%, and Recall of 61.8%. The robot was tested in two separate cotton fields, with rows around 20 meters long and the camera at 60 cm height for optimal real-time detection. The findings, compared to hand counts and confirmed against NDVI estimates, showed an average accuracy of 76.04% for B.T. Cotton and 67.54% for Organic Cotton fields. This study demonstrates the effectiveness of the proposed system in accurately detecting and managing crop threats. Combining ROS, drones, NDVI calculations, and a robust detection model, it provides a scalable approach for autonomous crop monitoring and protection, with the potential for broader agricultural adoption.

Electronic skin is widely employed in multiple applications such as health monitoring, robot tactile perception, and bionic prosthetics. In this study, we fabricated millimeter-scale electronic skin featuring compact sensing units using Boston Micro Fabrication S130 (a high-precision additive manufacturing device) and the template removal method. We used a gallium-based liquid metal and achieved an inner channel diameter of 0.1 mm. The size of the sensing unit was 3 × 3 mm². This unit exhibited a wide linear sensing range (10–22000 Pa) and high pressure resolution (10 Pa) even on an ultracurved surface (radius of curvature was 6 mm). Sliding was successfully detected at speeds of 8–54 mm/s. An artificial nose with nine sensing units was fabricated, and it exhibited excellent multitouch and sliding trajectory recognition capabilities. This confirmed that the electronic skin functioned normally even on an ultracurved surface.

In Kenya, reports of Rift Valley fever (RVF), one of the worst climate-sensitive zoonosis, have been common. Despite the fact that several empirical studies have demonstrated that Machine learning techniques perform better than time series models in forecasting time series data, there is little evidence of their use in predicting disease outbreaks in Africa. Recently, the literature has mentioned a number of other uses of machine learning to support intelligent decision-making in the healthcare industry and public health but there is limited knowledge on the use of the XGBoost model in the prediction of disease outbreaks. Among the Kenyan provinces, Rift valley fever cases were more pronounced in Rift valley (26.80%) and Eastern (20.60%) regions. The study explored the relationship be-tween RVF incidence and various climatic factors, such as humidity, clay content, elevation, slope, and rainfall. The strongest correlation, a meager 0.02903 for rainfall, was found in the correlation matrix, which showed weak linear relationships between various climatic factors and RVF cases. These climate variables were used to train the XGBoost model, which showed remark-able performance with an AUC of 0.8908, accuracy of 99.74%, precision of 99.75%, and recall of 99.99%. Rainfall was found to be the most important predictor in the feature importance analysis. These findings are consistent with other research showing how important weather conditions are to RVF outbreaks. According to the study's findings, the use of sophisticated machine learning models that take a variety of climatic factors into account can greatly improve RVF outbreak prediction and control.

Ranked Set Sampling (RSS) is a useful technique for improving the estimator of population mean when the sampling units in a study can be easily ranked than the actual measurement. RSS performs better than simple random sampling (SRS) when the mean of units corresponding to each rank is used. The performance of RSS can be increased further by assigning weights to the ranked observations. In this paper, we propose weighted RSS procedures to estimate the population mean of positively skew distributions. It is shown that the gain in the relative precisions of the population mean for chosen distributions are uniformly higher than those based on RSS. The gains in relative precisions are substantially high. Further, the relative precisions of our estimator are slightly higher than the ones based on Neyman’s optimal allocation model for small sample sizes. Moreover, it is shown that, the performance of the proposed estimator increases as the skewness increases by using the example of lognormal family of distributions.

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.