Mycobacterium tuberculosis (Mtb) is the etiological agent of tuberculosis (TB), a disease that alt-hough preventable and curable, remains a global epidemic due to the emergence of resistance and a latent form responsible for a long period of treatment. Drug discovery in TB is a challenging task due to the heterogeneity of the disease, the emergence of resistance and an uncomplete knowledge of the pathophysiology of the disease. The limited permeability of the cell wall and the presence of multiple efflux pumps remain a major barrier to achieve effective intracellular drug accumulation. While the complete genome sequence of Mtb has been determined and several potential protein targets have been validated, the lack of adequate models for in vitro and in vivo studies is a limit-ing factor in TB drug discovery programs. In current therapeutic regimens, less than 0.5% of bac-terial proteins are targeted being the biosynthesis of the cell wall and the energetic metabolism two of the most important processes exploited for TB chemotherapeutics. This review provides an overview on the current challenges in TB drug discovery and emerging Mtb druggable proteins, and how chemical probes for protein profiling enabled the identification of new targets and bi-omarkers, paving the way to disruptive therapeutic regimens and diagnostic tools.

Online speech enhancement is of great interest, because of its diverse areas of application. The Demucs architecture has been recently shown to achieve a high level of performance, even with small audio segments, while requiring a relatively small amount of computational resources. However, an issue that it bears, as well as most of state-of-the-art speech enhancement techniques, is that of target speech selection: it is assumed that only one speech source is present. However, in real-life scenarios, more than one speech source may be present, in it is uncertain which speech source within the fed mixture should be enhanced. Thus, it is of interest to complement speech enhancement techniques (such as Demucs-based) with a target selection scheme, so as to ensure that only the source of interest is enhanced. In this work, two target selection strategies are explored: 1) an embedding-based strategy, using a codified sample of the target speech, and 2) a location-based strategy, using a beamforming-based pre-filter to select the target that is in front of a 2-microphone array. It is shown that while both strategies improve the performance of the Demucs-based technique when one or more speech interferences are present, they both have their pros and cons. Specifically, while the beamforming-based strategy achieves overall a better performance compared to the embedding-based strategy, it is sensitive against the location variation of the target speech source which the embedding-based strategy does not suffer from.

Portfolio weights solely based on risk avoid estimation error from the sample mean, but they are still affected from the misspecification in the sample covariance matrix. To solve this problem, we shrink the covariance matrix towards the Identity, the Variance Identity, the Single-index model, the Common Covariance, the Constant Correlation and the Exponential Weighted Moving Average target matrices. By an extensive Monte Carlo simulation, we offer a comparative study of these target estimators, testing their ability in reproducing the true portfolio weights. We control for the dataset dimensionality and the shrinkage intensity in the Minimum Variance, Inverse Volatility, Equal-risk-contribution and Maximum Diversification portfolios. We find out that the Identity and Variance Identity have very good statistical properties, being well-conditioned also in high-dimensional dataset. In addition, the these two models are the best target towards to shrink: they minimise the misspecification in risk-based portfolio weights, generating estimates very close to the population values. Overall, shrinking the sample covariance matrix helps reducing weights misspecification, especially in the Minimum Variance and the Maximum Diversification portfolios. The Inverse Volatility and the Equal-Risk-Contribution portfolios are less sensitive to covariance misspecification, hence they benefit less from shrinkage.

Drug discovery utilizes high-throughput screening (HTS) methods applying target and cell-based assays. This review discusses the challenges and benefits associated with these assays in HTS. Discussed the strategies that can be applied for the development of screening assays through primary and secondary screens for target identification. Further discussion on identify-ing the most efficacious drugs following these approaches in cancer. Even though various drugs have been identified to treat cancer, there is high demand of more relevant phenotypic assays to produce desired diseased phenotype to only highlighting the specific targets instead of off-targets. Hopefully, the new developing strategies could provide innovative drugs to treat cancer patients to reduce mortality rate.

Sea cucumber detection represents a significate step in underwater environmental perception, which is an indispensable part of the intelligent subsea fishing system. However, various complex factors such as water turbidity declines the clarity of underwater images, presenting a challenge to vision-based underwater target detection. Therefore, accurate, real-time and lightweight detection models are required. First of all, the development of subsea target detection is summarized in this presented work. Besides, since target detection methods based on deep learning such as YOLOv5 and DETR, which are respectively examples of one-stage and anchor-free deep leaning methods, have been increasingly applied in underwater detection scenarios. Based on the analysis of state-of-the-art underwater sea cucumber detection approaches and aiming to provide a reference for practical subsea identification, the sea cucumber detection based on the YOLOv5 and DETR are investigated and compared in detail. For each approach, the detection experiment is carried out on the derived dataset which contains a wide variety of sea cucumber sample images. The compared experiments demonstrate that the overall outperformance of YOLOv5 in terms of low computing consumption and high precision, particularly in detection of small and dense features. Nevertheless, the DETR exhibits rapid development and holds promising prospects in underwater object detection applications, owing to its relatively simple architecture and ingenious attention mechanism.

Background: The target volume for post-mastectomy radiation therapy (PMRT) in breast cancer patients with reconstruction has been a subject of debate. This study aimed to assess the radiation dose distribution and treatment outcomes associated with different chest wall (CW) delineation according to ESTRO ACROP guideline for patients underwent implant-based reconstruction. Methods: We conducted a retrospective review of breast cancer patients who underwent mastectomy followed by two-stage implant-based breast reconstruction and adjuvant radiation therapy (RT) between 2007 and 2022. The expanders/implants were positioned retropectorally. The chest wall target volumes were categorized into two groups: the prepectoral group, which excluded the deep lymphatic plexus, and the whole expander group. Results: The study included 26 patients, 15 in prepectoral group and 11 in whole expander group. No significant differences were observed in normal organs exposure between the two groups. There was a trend toward a lower ipsilateral lung mean dose in the prepectoral group (10.2 vs. 11.1 Gy, p=0.06). Both groups exhibited limited instances of reconstruction failure and local recurrence. Conclusions: For patients undergoing two-stage expander-implant retropectoral breast reconstruction and PMRT, our data have provided comparable outcomes and normal organs exposure for those omitting the deep lymphatic plexus.

Drug design is used for different applications of bioinformatics tools analyze DNA, genome, and sequence target region of a small organic molecule in order to understand the molecules of disease. Bioinformatics tools are identified a newly wide research field and minimize future risks through web servers and data mining. Clinical sample test performed with the bioinformatics tools as the biomedical detective. A particular structure and configuration of protein obliging in Drug design concluded Bioinformatics. This review bioinformatics tools and webserver will discuss functions of small organic molecules according to clinical pharmacology.

Visual Sensor Networks (VSNs) have been the focus of numerous studies, emphasizing the quality of the information they generate. The primary goal of these networks is to capture data from an area, extract the pertinent information from the visual scene, and facilitate communication. However, the presence of objects in the study area can impacted the network's efficiency, linking the quality of acquired data directly to the positioning of the cameras. Strategically positioning multiple cameras in a potentially complex area, while ensuring effective communication between nodes, presents a challenging issue in VSNs applications. This paper introduces a specific method to enhance the deployment of visual sensors in indoor environments. The research addresses the theme of multi-objective optimization of VSN deployment, integrating various criteria: maximizing overall visual coverage, maximizing the observation of zones of interest, maximizing observation redundancy of zones of interest and ensuring communication connectivity for data transfers. To tackle this problem, we simulate the observed environment incorporating cameras, obstacles, and considering zones of interest. Camera positioning is performed while considering visual constraints and the scene's characteristics. The quality of positioning is evaluated based on the defined objective functions. Initially, a comparative study is conducted with a state-of-the-art approach, integrating the first three objective functions. Subsequently, we incorporate the fourth objective function to ensure data transfers. The proposed method demonstrates efficient camera network deployments in indoor areas, considering global coverage and observation redundancy. In contrast to the state-of-the-art, these results are achieved in areas with visual obstacles while ensuring communication connectivity between the different cameras.

Trypanosomatids are mainly responsible for leishmaniasis, sleeping sickness, and Chagas disease, which are the most challenging among the neglected tropical diseases due to the problem of drug resistance. Although problems of target deconvolution and polypharmacology are encountered, a target-based approach is a rational method for screening drug candidates targeting a biomolecule that causes diseases. The present study aims to summarize the latest information re-garding potential inhibitors of squalene synthase and farnesyl phosphate synthase with anti-Trypanosomatidae activity. The information was obtained by referencing textbooks and major scientific databases from their inception until April 2023. Based on in vitro experiments, more than seventy compounds were reported to inhibit squalene synthase and farnesyl diphosphate synthase. Among these compounds, more than 30 were found to be active in vitro against Trypanosomatidae, inferring that these compounds can be prospected as scaffolds for the development of new drugs against trypanosomatid-related infections. Over-all, natural and synthetic products can inhibit enzymes that are crucial for the survival and virulence of trypanosomatids. Moreover, in vitro experiments have confirmed the activity of more than half of these inhibitors using cell-based as-says. Nevertheless, additional studies on the cytotoxicity, pharmacokinetics, and lead optimization of potent anti-Trypanosomatid compounds should be investi-gated.

Due to their increased surface area, extent of swelling and active substance loading capacity and flexibility, nanogels made from natural and synthetic polymers have gained significant interest in the scientific and industrial areas. Especially, customized design and implementation of non-toxic, biocompatible, and biodegradable micro/nano carriers makes their usage very feasible for a range of biomedical applications, including drug delivery, tissue engineering, and bioimaging. The design and application methodologies of nanogels have been outlined in this review. Additionally, the most recent advancements in nanogel biomedical applications have been discussed, with a particular emphasis on applications for the delivery of drugs and biomolecules.

There are dozens of approved, investigational and experimental antiviral agents. Many of these agents cause serious side effects, which can be revealed only after drug administration. Identification of the side effects prior to drug administration is challenging. Here we describe an ex vivo approach for studying immuno- and neuro-modulatory properties of antiviral agents, which could be associated with potential side effects of these therapeutics. The approach combines drug toxicity/efficacy tests and transcriptomics, which is followed by cytokine and metabolite profiling. We demonstrated the utility of this approach with several examples of antiviral agents. We also showed that the approach can utilize different immune stimuli and cell types. It can also include other omics techniques, such as genomics and epigenomics, to allow identification of individual markers associated with adverse reactions to antivirals with immuno- and neuro-modulatory properties.

Financial markets require a great deal of decision making from the investors and market makers. One metric that can help ease the process of decision making is investment risk which can be measured in two parts; systematic risk and idiosyncratic risk. Clear understanding of the volatilities in each risk component can be a powerful signal in recognizing the right assets to maximize the investment returns. In this paper, we focus on the idiosyncratic volatility values and pre-calculate the idiosyncratic volatility values for 31,198 members of NYSE, Amex and Nasdaq markets for the trades occurring between January 1963 and December 2019. Utilizing a subset of dataset, limited to Nasdaq100 index, we consider the application of machine learning techniques in predicting the idiosyncratic volatility values using the raw trade data to explore a data extension option for the future market trade records that have not yet occurred. We offer a deep learning based regression model and compare it with traditional tree-based methods on a small subset of our per-calculated idiosyncratic volatility dataset. Our analytical results show that the performance of the deep learning techniques is much more robust in comparison to that of the traditional tree-based baselines.

In his Cynefin classification of system behaviours, Snowden (2007), posits that his Simple (Clear ) and even Complicated system categories are sufficiently understandable to be amenable to the traditional methods of system analysis and modelling. Here, relationships between entities in the system are clear and unambiguous and they behave predictably. So, we can build mathematical “models” to describe how the system is expected to function in different situations. Leaving aside his fourth category, Chaotic, as too hard for the moment, this paper focusses on the third category, Complex systems. Yaneer Bar-Yam [1998] defined "complex systems" as systems that "have multiple interacting components, whose collective behaviour cannot be simply inferred from the behaviour of components." So, the traditional system modelling approach of decomposition into components and attempting to build up a picture of system performance from individual pieces, alone, is no longer appropriate for this class. The problem is that most of the methods we currently employ, and particularly the methods that attempt to make the case that these systems are safe, (such as Fault trees, FMEA. and Root Cause Analysis), rely on this decomposition into components and attempt to make the parts more reliable individually. Even the more systemic approaches, such as Reason’s (1990) Swiss Cheese Model, and Leveson’s System Theoretic Analysis (STPA) (2004), encourage adding layers of protection, barriers, strengthened control loops and better safety critical systems, in the hope that they are making the systems safer. But without a valid model to test the effectiveness of these add-ons, we cannot be sure that they will not have an opposite effect, of making the systems even more complex, unreliable and unpredictable. For complex systems, the careful gathering and documentation of system components and their relationships is still a necessary first step, but we need an additional capacity to model these complex systems to test out and prove they work safely and successfully in the real world. (not just draw fixed component relationships as system “models” (wiring diagrams)) In the last 10 years, an original approach developed by Hollnagel, (2012), to model systems as sets of interactive, interdependent “functions”, (abstracted from and independent of component details), has now been developed to the point where it can take the basic data and structures from the current component focussed system engineering “models”, such as MBSE( Goldberg (1994)), and can pull it all together in a dynamic system model from which analysts can discern how it really works in practice, and predict the emergent behaviours characteristic of complex systems. The paper describes how this methodology developed and how it is currently used to model real situations, to analyse incidents and anticipate events.

The proliferation of SARS-COV-2 through enhanced viral replication and its subsequent triggering of cytokine storm, are some of the hallmark phenotypes in severe COVID-19 patient cases. Cyclosporine, an immunosuppressant drug and Selinexor, an inhibitor of nuclear transporter protein, both have been successfully demonstrated to be effective against SARS-COV-2 infection by targeting those functions individually. However, the highly multifactorial pathology of SARS-COV-2 infection hinders any mono-therapeutic strategy to become an optimal option. In this study, we assess the potential efficacy of the Cyclosporine-Selinexor combination on an integrated interactome by adopting a network-medicine-based repositioning technique, where disease proximity, functional proximity and their topological separation are evaluated, followed by a robust statistical significance test. Results have shown that both drug target modules are highly proximal to the SARS-COV-2 disease modules in terms of network topology and functional associations, in a statistically significant manner, individually. Functional enrichment of both drug modules and SARS-COV-2 infected modules has shown that two drugs target the functions related to viral replication and cytokine storm during infection. Moreover, a high degree of network separation been those two drug target modules has been observed, revealing ``complementary exposure`` patterns, rendering this drug combination as an effective one against SARS-COV-2 infection. We hope that our results will encourage researchers to further investigate the potency of Cyclosporine and Selinexor combination in vivo or in vitro, and ultimately lead that up to clinical trials to treat SARS-COV-2 patients.

Decision making as a result of system dynamics analysis requires, in practice, a straightforward and systematic modelling capability as well as a high-level of customisation and flexibility to adapt to situations and environments that may vary very much from each other. While in general terms a completely generic approach could be not as effective as ad-hoc solutions, the proper application of modern technology may facilitate agile strategies as a result of a smart combination of qualitative and quantitative aspects. In order to address such a complexity, we propose a knowledge-based approach that integrates the systematic computation of heterogeneous criteria with open semantics. The holistic understanding of the framework is described by a reference architecture and the proof-of-concept prototype developed can support high-level system analysis, as well as it suitable within a number of applications contexts - i.e. as a research/educational tool, communication framework, gamification and participatory modelling. Additionally, the knowledge-based philosophy, developed upon Semantic Web technology, increases the capability in terms of holistic knowledge building and re-use via interoperability. Last but not least, the framework is designed to constantly evolve in the next future, for instance by incorporating more advanced AI-powered features.

In this paper, a framework for simultaneous tracking and recognizing drone targets using a low-cost and small-sized millimeter-wave radar is presented. The radar collects the reflected signals of multiple targets in the field of view including drone and non-drone targets. The analysis of the received signals allows multiple targets to be distinguished because of the different reflection patterns. The proposed framework consists of four processes including signal processing, cloud points clustering, target tracking, and target recognition. Signal processing translates the raw signals into spare cloud points. These points are merged into several clusters, each representing a single target. Target tracking estimates the new locations of each detected target. A novel convolutional neural network model is developed for drone and/or non-drone targets feature extraction and recognition. For performance evaluation, a dataset collected with an IWR6843ISK mmWave sensor by Texas Instruments is used for training and testing the convolutional neural network. The proposed recognition model achieves an accuracy of 98.4% for one target and 98.1% for two targets.

Pedestrian multi-target tracking technology plays an important role in artificial intelligence, driverless, virtual reality and other fields. The pedestrian multi-target tracking algorithm DeepSORT based on detection is widely used in industry. It mainly tracks multiple pedestrian targets continuously and keeps their ID unchanged. In order to improve the applicability and tracking accuracy of DeepSORT algorithm, this paper improved the IOU distance measurement in the matching process. At the same time, ResNet50 is used as the feature extraction backbone network, and combined with FPN (Feature Pyramid Network), the appearance features of multi-layer pedestrians are fused to improve the tracking accuracy of DeepSORT algorithm. The proposed algorithm is verified on the public data set MOT-16 and it’s tracking accuracy is enhanced to 4.1%.

List-only entity linking is the task of mapping ambiguous mentions in texts to target entities in a group of entity lists. Different from traditional entity linking task, which leverages rich semantic relatedness in knowledge bases to improve linking accuracy, list-only entity linking can merely take advantage of co-occurrences information in entity lists. State-of-the-art work utilizes co-occurrences information to enrich entity descriptions, which are further used to calculate local compatibility between mentions and entities to determine results. Nonetheless, entity coherence is also deemed to play an important part in entity linking, which is yet currently neglected. In this work, in addition to local compatibility, we take into account global coherence among entities. Specifically, we propose to harness co-occurrences in entity lists for mining both explicit and implicit entity relations. The relations are then integrated into an entity graph, on which Personalized PageRank is incorporated to compute entity coherence. The final results are derived by combining local mention-entity similarity and global entity coherence. The experimental studies validate the superiority of our method. Our proposal not only improves the performance of list-only entity linking, but also opens up the bridge between list-only entity linking and conventional entity linking solutions.

Model-based approaches form the basis of the majority of damage detection and localization studies; however, built-in online detection technique can offer an alternative for future structural health monitoring technologies. Thus, in this paper, we present a dynamic localization algorithm for damage localization in functionally graded plates. The method depends on the creation of a grid matrix that contains the dynamic response of the structure over time. Subsequently, an optimization process is carried out via a linear equation representing the information contained within the grid to achieve accurate localization of damage. Due to the inherent sparsity of the localization nature, the FISTA algorithm has been employed as a problem solver. The approach is tested in the case of the functionally graded plate under clamped free boundary conditions. Several, damage scenarios were investigated for the case of damage signals on and off the grid. The results show that the proposed approach is capable of accurately predicting damage position and can be suitable for use in low size data systems.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Its treatment includes antiarrhythmic drugs (AADs) to modulate the function of cardiac ion channels. However, AADs have been limited by proarrhythmic effects, non-cardiovascular toxicities as well as often modest antiarrhythmic efficacy. Theoretical models showed that combined blockade of Nav1.5 (and its current INa) and Kv1.5 (and its current, IKur) ion channels yield a synergistic anti-arrhythmic effect without effect on ventricles. We focused on Kv1.5 and Nav1.5 to search for structural similarities in their binding site (BS) for flecainide (a common blocker and widely prescribed AAD), as a first step for prospective rational multi-target directed ligand (MTDL) design strategies. We presented a computational workflow for flecainide BS comparison in a flecainide-Kv1.5 docking model and a solved structure of flecainide-Nav1.5 complex. The workflow includes docking, molecular dynamics, BS characterization and pattern matching. We identified a common structural pattern in flecainide BS for these channels. The latter belongs to the inner cavity and consist of a hydrophobic patch and a polar region, involving residues from S6 helix and P-loop. Since the rational MTDL design for AF is still incipient, our findings could advance multi-target atrial-selective strategies for AF treatment.

The integration of bioinformatics in drug discovery has revolutionized the field of pharmaceutical research. The use of computational tools and techniques has enabled researchers to analyze vast amounts of data, identify potential drug targets, and design new drugs with greater precision and efficiency. The integration of bioinformatics has also facilitated the development of personalized medicine, where drugs can be tailored to individual patients based on their genetic makeup. However, there are still challenges that need to be addressed, such as the need for more accurate predictive models and the ethical considerations surrounding the use of patient data. Overall, the integration of bioinformatics in drug discovery holds great promise for improving human health and advancing our understanding of disease mechanisms. In this mini-review, we discuss how Bioinformatics plays a crucial role in each step of drug discovery by providing tools and techniques to analyze large amounts of data generated from various sources, as well as the challenges and the opportunities offered by bioinformatics.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by swelling in at least one joint. Owing to an overactive immune response, extra-articular manifestations are observed in certain cases, with interstitial lung disease (ILD) being the most common. Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is characterized by chronic inflammation of the interstitial space, which causes fibrosis and the scarring of lung tissue. Controlling inflammation and pulmonary fibrosis in RA-ILD is important because they are associated with high morbidity and mortality. Pirfenidone and nintedanib are specific drugs against idiopathic pulmonary fibrosis and have shown efficacy against RA-ILD in several clinical trials. Immunosuppressants and disease-modifying antirheumatic drugs (DMARDs) with antifibrotic effects have also been used to treat RA-ILD. Immunosuppressants moderate the overexpression of cytokines and immune cells to reduce pulmonary damage and slow the progression of fibrosis. DMARDs with mild antifibrotic effects target specific fibrotic pathways to regulate fibrogenic cellular activity, extracellular matrix homeostasis, and oxidative stress levels. Therefore, specific medications are required to effectively treat RA-ILD. In this review, the commonly used RA-ILD treatments are discussed based on their molecular mechanisms and clinical trial results. In addition, a computational approach is proposed to develop specific drugs for RA-ILD.

Previously, we described the initial use of Flipped Team‐Based learning (FTBL) defined as TBL approach combined with flipped classroom learning methodology, in which students previewed online lectures and applied their knowledge in different in-class activities. The purpose of the present study is to review the progress within this approach and to investigate how constant changes in team allocation can affect student’s perception regarding this modified FTBL approach. Although students showed reluctance initially to get out of their ‘comfort zone’, our findings show that learners perceived the adoption of the continued random allocation, and became accustomed to this learning approach, which finally assisted them to enhance their team-work skills and classroom performance, to develop their reflective capabilities as well as improving their rapport building skills, learning and academic performance. Learners also believed that this learning strategy that creates critical incidents can simulate their future work environment as they might be expected to work in unfamiliar situations. Therefore, the present study indicated strong support for the modified FTBL method and was seen to work exceptionally well, despite some minor problems that students can experience working in a team and/or with different teammates in every session.

The complexity of modern power grids, exacerbated by integrating diverse energy sources, espe-cially inverter-based resources (IBRs), presents a significant challenge to grid operation and plan-ning since linear models fail to capture the intricate IBR dynamics. This study employs the Sparse Identification of Nonlinear Dynamics (SINDy) method to bridge the gap between theoretical un-derstanding and practical implementation in power system analysis. It introduces the novel Volterra-based Nonlinearity Index (VNI) to examine system-level nonlinearity comprehensively. The distinction of dynamics into first-order linearizable terms, second-order nonlinear dynamics, and third-order noise elucidates the intricacy of power systems. The findings demonstrate a fundamental shift in system dynamics as power sources transit to IBRs, revealing system-level nonlinearity compared to module-level nonlinearity in conventional syn-chronous generators. The VNI quantifies nonlinear-to-linear relationships, enriching our comprehension of power system behavior and offering a versatile tool for distinguishing between different nonlinearities and visualizing their distinct patterns through the proposed VIN profile.

Process mining offers significant services in the development of digital threads and digital twin applications for healthcare. One of the sub-emerging case studies is the use of patients’ location data in process mining analyses. While the streamlining of published works is focused on introducing process discovery algorithms, there is a necessity to address challenges beyond that. Literature analysis indicates that explainability, reasoning, and characterizing the root causes of process drifts in healthcare processes is an important but overlooked challenge. In addition, incorporating domain-specific knowledge into process discovery could be a significant contribution to process mining literature. To address this, we present the DIAG approach that consists of a meta-model and an algorithm that enables diagnosing in process mining through an ontology-driven approach. With DIAG, we modeled the healthcare semantics in a process mining application and diagnosed the causes of drifts in patients’ pathways. We performed an experiment in a hospital living lab to examine the effectiveness of the DIAG approach.

The development of biosensors for target detection plays a crucial role in advancing various fields of bioscience. This work presents the development of a genosensor that exploits the colorimetric phenol-sulfuric acid sugar reaction for the detection of DNA, and RNA as specific targets, and DNA intercalator molecules. The biosensor combines simplicity and reliability to create a novel bio-assay for accurate and rapid analysis. A 96-well microplate based on polystyrene polymer was used as the platform for an unmodified capture DNA immobilization via a silanization process and with (3-Aminopropyl) triethoxysilane (APTES). After that, a hybridization step was carried out to catch the target molecule, followed by adding phenol and sulfuric acid to quantify the amount of DNA or RNA sugar backbone. This reaction generates a yellow-orange color on the wells measured at 490 nm that was proportional to the target concentration. Under the optimum conditions, a calibration curve was obtained for each target. The developed biosensor demonstrated high sensitivity, good selectivity, and linear response over a wide concentration range for DNA and RNA targets. Additionally, the biosensor was successfully employed for the detection of DNA intercalator agents that inhibit the hybridization of DNA complementary to the immobilized capture DNA. The developed biosensor offers a potential tool for sensitive and selective detection in various applications, including virus diagnosis, genetic analysis, pathogenic bacteria monitoring, and drug discovery.

The COVID-19 was described as a respiratory illness, however further studies recognize it as a complex heterogeneous multisystemic disorder. Global efforts have been proposed to combat COVID-19, emerging diverse therapeutic options, in which discovering new drug therapies, development of vaccines and drug repurposing have been considered the most promising approaches to fight the virus. This study aimed to repurpose known drugs for use against the COVID-19, finding better therapeutic options. Seventeen biological databases were used in this study. The genetic algorithm (GA) was performed for a set of drug target classes and COVID-19 proteins as input, whose drug candidates are obtained according to the target similarities found in the target-target similarity predictive network, resulting in a drug-target interaction network. Thus, recommended drugs correspond to the union of the drug subsets found during each GA execution. Twenty-eight drugs were indicated to be the best therapeutic targets for the virus, in special, the Cyclosporine drug was administered as adjuvant to steroid treatment for COVID-19 patients which showed positive outcomes, reducing mortality in moderate and severe cases. The drugs found have used to treat other diseases, evidencing that the COVID-19 is a multisystemic disorder and suggests that the viruses’ mechanism of action presents some comorbidity with other human diseases. Evidence shows that the drugs found in this research might act together to fight the virus in a broader fashion, however further studies including in vitro and in vivo experiments are needed to find the best combination of these drugs.

We present a new model formulation for a class of capacitated lot-sizing problem considering setup costs, product returns, and remanufacturing (CLSP-RM). We investigate a broad class of instances that fall into two groups, in the first group we can reformulate the problem with a relaxation and test whether the original problem is solvable. The relaxation gives near optimal solutions and the solution of this class does not give any difficulty to known solvers such as Cplex, Gurobi or Xpress. The second group of instances are of category NP and will be solved with a simple period-by-period simulation

Over the past decade, Knowledge bases (KB) have been increasingly utilized to complete and enrich the representation of queries and documents in order to improve the document retrieval task. Although many approaches have used KB for such purpose, understanding how effectively lev-erage entity-based representation still needs to be resolved. This paper proposes a Purely Enti-ty-based Semantic Search Approach for Information Retrieval (PESS4IR) as a novel solution. The approach includes (i) its own entity linking method, (ii) an inverted indexing method, and for document retrieval and ranking, (iii) an appropriate ranking method is designed to take advantage of all the strengths of the approach. We report the findings on the performance of our approach tested by queries annotated by two known entity linking tools, REL and DBpedia-Spotlight. The experiments are performed on the standard TREC 2004 Robust and MSMARCO collections. By using the REL method, for queries whose all terms are annotated and whose average annotation scores are greater than or equal to 0.75, our approach achieves the maximum nDCG@5 score (1.000). Thus, using our approach with any other document retrieval method would be an added value, unless that method achieves the maximum nDCG@5 score for those highly annotated queries.

Adaptation to the impacts of human induced global heating is inevitable. For a socially just and ecological sustainable adjustment to these new circumstances, we need to draw from diverse knowledge systems while, simultaneously, foster a social-ecological transformation. We approach these concerns through the concept of community-based adaptation (CBA) and discuss remedies. Synergies with feminist knowledge systems and indigenous ways of living show the transdisciplinary essence of CBA. By abstracting from its origin and overlapping disciplines, revealing the social metabolism as a common problem, CBA is prone to achieve more equitable and sustainable adjustments. Transdisciplinarity itself and the current related CBA literature point beyond mere adjustments and call for a redesign of the social metabolism, thereby shifting from adaptation to global heating towards adaptation with nature by focusing on social provisioning. An engagement with transformative adaptation and heterodox economics further shows the potential of CBA to serve as an instrument in support of a social-ecological transformation by addressing root causes of vulnerability and by fostering epistemic justice. Reflecting these points back on the epistemological and ontological assumptions of CBA, the viewpoint proposes critical realism as a guiding philosophy of science to move forward.

An accurate and timely precipitation forecast is essential for water resources management in hydropower, irrigation, and reservoir control. The conventional methods are limited by their inability to capture the high precipitation variability in time and space. In the present work, a wavelet-based deep learning approach is adopted to forecast precipitation using the lagged monthly rainfall, local climate variables, and global teleconnections such as IOD, PDO, NAO, and Nino 3.4 as predictors. The method was tested and validated over the Krishna River Basin in India. Overall, the forecasting accuracy was higher using the wavelet-based hybrid models than the single-scale models. The proposed multi-scale model was then applied to the different climatic regions of the country, and it was shown that the model could forecast the rainfall at reasonable accuracy for different climate zones of the country.

Purpose: Now traditional lecture-based teaching and learning have been affected by the COVID-19. The objectives of this article are to design the novel educational technique called ‘dynamic-based learning’ (DBL) that provides the combination of online teaching-learning methods and student’s creativity, to evaluate primary dynamic-based learning function, and to propose dynamic-based learning for higher education. Methods: DBL composes of four steps, including, preparation, homework, classroom, and evaluation, which was designed, and taught in medical and dental schools. Online support materials included mobile phone, email, Facebook Messenger, Line Messenger, Cisco Webex, and Zoom Meetings applications were recruited for this novel method. Results: A total of 32 third-year medical students and 26 sixth-year dental students was treated by DBL similarly. three subjects, including, Innovation in Dentistry, Basic Medical Research, and Principles of Pathology and Forensic Medicine were selected in this article. The results showed students could create their knowledge, ideas, and creativity during the online classes.Conclusion: DBL can be used as an alternative learning mode during the COVID-19 crisis. The benefits of DBL also include high flexibility, dynamic process, active learning, and high creativity. DBL should be tested with other disciplines such as engineering school, laws school, health sciences school, and should be compared with other traditional teaching and learning modes in the future. This method may support the global higher education systems to move forward the COVID-19 pandemic to set a novel standard of a future normal.

In an increasingly complex world there is a real, urgent need for methodologies to enable engineers to model complex sociotechnical systems, as these now seem to describe the majority of systems in use today. This is of course exacerbated by the increasing involvement and augmentation with “black box” AI contributions. Hollnagel produced a methodology, (FRAM) which did allow the analyst in-sights into these systems’ behaviour, but the model-based system engineering applications demand numbers and a quantitative ap-proach. In the last 10 years, this original approach developed to model systems as sets of interactive, interdependent “functions”, (abstracted from agent or component details), has been further developed to the point where it can take the basic data and structures from the current component focussed system engineering “models”, and can pull it all together into dynamic models, (as opposed to static, fixed System Theoretic Process Accimaps), from which analysts can discern how they really work in practice, and predict the emergent behaviours characteristic of complex systems. This paper describes how the FRAM methodology has now been extended to provide these extra, essential attributes. It also describes its implementation using an open-source software, freely available for use and verification on the GitHub site.

Time and cost-efficient techniques are essential to avoid extra conventional experimental studies with large date-set to characterize the mechanical properties of composite materials. Correlation between the structural performance and mechanical properties could be captured through the efficient predictive models. Several ensembled Machine Learning (ML) methods were implemented in this study, to materially characterize carbon nanotube (CNT)-reinforced cement-based composites. Proposed models were compared with each other to represent the accuracy of each method. The Flexural and Compressive Strength (target values) of CNT reinforced composites were predicted based on the data-rich framework provided in previous experimental investigations. These data were utilized for training of the proposed models by employing SciKit-Learn library in Python, followed by hyper-parameter tuning and k-fold cross-validation method for obtaining an efficient model to predict the target values. Random Forest (RF) and Gradient Boosting Machine (GBM) were developed for this purpose. The findings of this study would be useful for prospective composite designers in case of sufficient experimental data availability for ML model training.

Lung cancer represents the most common form of cancer accounting for 1.8 million deaths globally in 2020.The 5-year relative survival rate for lung cancer is lower than many other leading cancer types. Over the last decade the treatment for advanced and metastatic non small cell lung cancer have dramatically improved due to the development of immune checkpoint inhibitors and the identification of targetable driver mutations. Recently, potentially effective inhibitors of a hitherto untargetable oncogenic driver mutation in NSCLC, Kirsten Rat Sarcoma (KRAS) have been developed. KRAS mutations are found in 20-25% of NSCLC and represent the most frequent mutation. The mutation is almost exclusively detected in adenocarcinoma and is found among smokers 90% of the time. Along with the development of new drugs that have been showing promising activity, resistance mechanisms have begun to be clarified. The aim of this review is to unwrap the biology of KRAS in NSCLC with a specific focus on primary and secondary resistance mechanisms and their possible clinical implications.

This paper investigates the theoretical foundation for developing renewable geothermal resources locally. For this reason, we pay attention to the role of communities in geothermal development. This study presents arguments for a framework that approaches the geothermal resources as an endogenous factor of community development. To analyse it, we create a model that explains the local economic characters of the geothermal exploitation beyond its geological conditions. It aims to conceptualise a community based geothermal development standard referring to the endogeneity principle. Geothermal energy is given attention since the characteristics of this resource determine its use locally. We argue that the role of communities in geothermal exploitation is pivotal in the process of green growth for further expansion of geothermal energy use.

This study assesses the impact of incorporating an adaptive learning mechanism into an agent-based model (ABMS) simulating behavior on a university campus during the course of a pandemic outbreak, with a particular case on the COVID-19 pandemic. The aim is to reduce overcrowding and infections on campus through the use of Reinforcement Learning (RL). Our findings indicate that RL is a viable approach for effectively representing agents’ behavior within this context. The results reveal specific temporal patterns of overcrowding violations. While our study successfully mitigated campus crowding, it had limited influence on altering the course of the epidemic. This highlights the necessity for comprehensive epidemic control strategies that consider the role of individual decision-making influenced by adaptive learning, along with the implementation of targeted interventions. This research significantly contributes to our understanding of adaptive learning within complex systems and offers valuable insights for shaping future public health policies in similar community settings. Future research directions encompass exploring various parameter settings and updating representations of the disease’s natural history.

Evidence-based data for endometriosis management are limited. Experiments are excluded without adequate animal models. Data are limited to symptomatic women and occasional observations. Hormonal medical therapy cannot be blinded if recognised by the patient. Randomised controlled trials are not realistic for surgery since a variable disease with low numbers. Each diagnosis and treatment is an experiment with an outcome and experience is Bayesian updating from the past. If the experience of many is similar, this has more value than an opinion. The combined experience of a group of endometriosis surgeons was used to discuss problems in the management of endometriosis. Considering endometriosis as several genetically/epigenetically different diseases is important for medical therapy. Imaging cannot exclude endometriosis and diagnostic accuracy is limited for superficial lesions, deep lesions, and cystic corpora lutea. Surgery should not be avoided for emotional reasons. Shifting infertility treatment to IVF without considering fertility surgery is questionable. The concept of complete excision should be reconsidered. Surgeons should introduce quality control and teaching should move to explain why it is done. The perception of information has a personal bias. These are the major problems in the management of endometriosis identified by the combined experience of endometriosis surgeons.

Unmanned surface vehicles have the advantages of maneuverability, concealment, wide activity area and low cost of use. Therefore, they have broad application prospects. This makes unmanned surface vehicles a research hotspot at home and abroad, and the sensing technology is the basis for the unmanned surface vehicles to perform tasks. The perception technology based on optical vision has the advantages of convenient application, relatively low cost, easy data acquisition and large amount of information, and has been widely studied by scholars at home and abroad. This paper mainly discusses the research of optical vision in unmanned surface vehicles from five aspects: Firstly, the water surface image preprocessing based on unmanned surface vehicles, mainly including water surface image stabilization research and defogging enhancement research; two water boundary detection; It is the use of light vision target detection; the fourth is the surface target tracking method. Finally, the light vision research of unmanned surface vehicles is summarized and forecasted.

Stenting is a common method for treating atherosclerosis. A metal or polymer stent is deployed to open the stenosed artery or vein. After the stent is deployed, the blood flow dynamics influence the mechanics by compressing and expanding the structure. If the stent does not respond properly to the resulting stress, vascular wall injury or re-stenosis can occur. In this work, Discrete Multiphysics is used to study the mechanical deformation of the coronary stent and its relationship with the blood flow dynamics. The major parameters responsible for deforming the stent are sort in terms of dimensionless numbers and a relationship between the elastic forces in the stent and pressure forces in the fluid is established. The blood flow and the stiffness of the stent material contribute significantly to the stent deformation and affect the rate of deformation. The stress distribution in the stent is not uniform with the higher stresses occurring at the nodes of the structure.

In this paper, we introduce a non-invasive approach for monitoring bridge infrastructure with ground-based interferometric radar. This approach is called the mirror mode, since it utilises the flat surface of the bridge underside as a mirror to reflect the signal to a corner reflector on the ground placed opposite of the radar sensor. For proving the feasibility of this approach, a measurement campaign has been carried out at an exemplary bridge in Karlsruhe (Germany) including a radar sensor in mirror mode, a second radar sensor in the default mode and a laser profile scanner. We investigate the potential of this approach to monitor the bridge displacement in vertical direction and compare the results with the two other sensors. The derived results reveal the potential for monitoring bridge infrastructure. Finally, we propose further research aspects of this approach to analyse its capabilities and limitation in the context of non-invasive infrastructure monitoring.

Cadmium (II) contamination in the environment is an emerging problem due to its acute toxicity and mobility, so it is very urgent to remove this species from industrial wastewater before it is discharged into the environment. Thus, a starch-based activated carbon (AC) with a specific surface area of 1600 m2g-1 is used as an adsorbent for the capturing of toxic Cadmium (II) ions from synthetic solution. The sorbent is characterized by BET, SEM, TEM, XRD, FT-IR, TGA, and zeta potential. The maximum uptake (284 mg g-1) of Cadmium (II) ion is obtained at pH 6. The thermodynamics parameters like ∆G, ∆H, ΔS are found to be -17.42 kJmol-1, 6.49 kJ mol-1, and 55.66 Jmol-1K-1 respectively, revealing that the adsorption mechanism is endothermic, spontaneous, and feasible. The experimental data follows the D-R and Langmuir models well. The mass transfer is controlled by pseudo 2nd order kinetics. Furthermore, the density functional theory simulations demonstrate that the activated carbon strongly interacted with the Cd (II) ion through its various active sites. The adsorption energy noted for all interactive sites is highly negative (-0.45 eV to -10.03 eV), which shows that the adsorption process is spontaneous and stable which is in agreement with the experimental thermodynamics analysis.

In today's business world, many companies have realized that consumer feedback evaluations play a crucial part in shaping the company's future activities. The hotel and tourism industries are well-known examples where the user feedback has become crucial. Even though most accommodations want their clients to express their opinions about their services, these reviews are nevertheless carefully reviewed by them. This manual approach is time demanding and error prone, the level of expertise of the individual analyzing the evaluations determines the quality of the manual analysis. This research focuses on the development of a tool-based support system that analyzes text-based customer evaluations and then highlights the maintenance issues identified in the reviews, removing the need to manually evaluate and analyze the customer reviews. The process includes data preparation, sentiment analysis, and a fully trained deep learning model to extract critical insights. Using sentiment analysis techniques after data preprocessing and trained deep learning model, an accuracy of 96% was achieved, and this paper discusses how this technology helps to meet the needs of accommodation management by completing activities efficiently. This might save management time and helps to save money without losing clients, allowing them to enhance their additional sales.

This paper considers the detection of fluctuating target in heavy-tailed clutter through the use of dynamic programming based on track-before-detect (DP-TBD) in radar systems. The clutter is modeled in terms of K-distribution, which can be widely used to describe non-Gaussian clutter received from high-resolution radars and radars working at small grazing angle. Swerling type 1 is considered to describe the target fluctuation between scans. Conventional TBD techniques suffer from significant performance loss in heavy-tailed environments due to the more frequent occurrences of target-like outliers. In this paper, we resort to DP-TBD algorithm based on prior information, which can enhance the detection performance by using the environment and target fluctuating information during the integration process of TBD. Under non-Gaussian background, the expressions of the likelihood ratio merit function for Swerling type 1 target are derived first. However, the closed analytical form of the merit function is difficult to be obtained. In order to reduce the complexity of evaluating the merit function and the computational load, an efficient approximation method as well as a two-stage detection approach is proposed and used in the integration process. Finally, several numerical simulations of the new strategy and the comparisons are presented to verify that the proposed algorithm can improve the detection performance, especially for fluctuating target in heavy-tailed clutter.

To understand forest dynamics under today’s changing environmental conditions, it is important to analyze the state of forests at large scales. Forest inventories are not available for all regions, so it is important to use other additional sources of information, e.g. remote sensing observations. Increasingly, remotely sensed data based on optical instruments and airborne LIDAR are becoming widely available for forests. There is great potential in analyzing these measurements and gaining an understanding of forests state. In this work, we combine the new generation radiative transfer model mScope with the individual-based forest model FORMIND to generate reflectance spectra for forests. Combining the two models allows us to account for species diversity at different height layers in the forest. We compare the generated reflectances for forest stands in Finland, in the region of North Karelia, with Sentinel-2 measurements. We investigate which level of forest representation gives the best results. For the majority of the forest stands, we generated good reflectances with all levels forest representation compared to the measured reflectance. Good correlations were also found for the vegetation indices (especially NDVI with R²=0.62). This work provides a forward modelling tool for relating forest reflectance to forest characteristics. With this tool it is possible to generate a large set of forest stands with corresponding reflectances. This opens the possibility to understand how reflectance is related to succession and different forest conditions.

This comprehensive review elucidates the profound relationship between the human microbiome and breast cancer managrement. Recent findings highlight the significance of microbial alterations in tissues, such as the gut and the breast, and their role in influencing breast cancer risk, development, progression, and treatment outcomes. We delve into how the gut microbiome can modulate systemic inflammatory responses and estrogen levels, thereby impacting cancer initiation and therapeutic drug efficacy. Furthermore, we explore the unique microbial diversity within breast tissue, indicating potential imbalances brought about by cancer and highlighting specific microbes as promising therapeutic targets. Emphasizing a holistic One Health approach, this review underscores the importance of integrating insights from human, animal, and environmental health to gain a deeper understanding of the complex microbe-cancer interplay. As the field advances, strategic manipulation of the microbiome and its metabolites presents innovative prospects for enhancing cancer diagnostics and therapeutics. However, rigorous clinical trials remain essential to confirm the potential of microbiota-based interventions in breast cancer management.

Coal combustion in thermal power plants releases ash. Ash is reported to cause different adverse health hazards in humans and other organisms. Owing to the presence of radionuclides, it is also considered as a potential radiation hazard. In this study, based on the surface radiation measurements and relevant ancillary data, expected radiation risk zones were identified with regard to the human population residing near the Thermal Power Plant. With population density as the risk determining criteria, about 20% of the study area was at ‘High’ risk and another 20% of the study area was at ‘Low’ risk zone. The remaining 60% was under medium risk zone. Based on the findings remedial measures which may be adopted have been suggested.

Infection with the malaria parasite Plasmodium, remains a major cause of illness and death world-wide. The development of evasion strategies by the parasite from host immunity and its adaptability to antimalarial drugs has raised the urgency for developing new strategies to combat this disease. One promising avenue is targeting telomeres – sequences found at chromosome termini– and telomerase – the enzyme that catalysis synthesis of telomeres using an intrinsic RNA template. As telomeres shorten critically, cells undergo replicative senescence or apoptosis. Plasmodium, lacking telomerase activity in its human stages, exploits alternative mechanisms, accelerating telomere shortening, aging, and immune evasion. Chemical telomerase inhibitors show promise as antimalarials. In this review, we examine the potential of targeting this system in malaria therapy, with telomerase inhibitors offering a novel approach. A systematic search on PubMed using Boolean techniques identified 246 relevant articles from 1985 to March 31, 2024. After filtering, 43 articles met inclusion criteria, supplemented by snowball sampling. The telomerase inhibitor drug strategy is widely applicable against cancer. However, given the drugability of telomerase and the absolute requirement for active telomere maintenance in the vast majority of parasites including plasmodium, telomerase and telomere maintenance could well represent the Achilles heel of the parasite

Currently, ovarian cancer (OC) is a target of intense biomarkers research because of its frequent late diagnosis and poor prognosis. Serum determination of Human epididymis protein 4 (HE4) is a very important early detection test. Most interestingly, HE4 plays a unique role in OC as it has been implicated not only in OC diagnosis but also in the prognosis and recurrence of this lethal neoplasm, actually acting as a clinical biomarker. There are several evidence about the predictive power of HE4 clinically, conversely less has been described concerning its role in OC oncogenesis. Based on these considerations, the main goal of this review is to clarify the role of HE4 in OC proliferation, angiogenesis, metastatization, immune response and also in the development of targeted therapy. Through a deeper understanding of its functions as a key molecule in the oncogenetic processes underlying OC, HE4 could be possibly considered as an essential resource not only for diagnosis but also for prognosis and therapy choice.

MicroRNAs act as the cardinal post-transcriptional monitors of gene regulatory networks sculpturing the developmental plasticity and stress responses in plants. Single miRNA target several genes and how the transcriptional regulation of miRNA impacts its pool of targets in different tissues and stress conditions is still elusive. The present study investigated the highly conserved and evolving MIR408 family comprehensively by redefining its evolutionary conservation and diversification in plants followed by detailed functional analysis in rice. MIR408 family comprises three dominant mature forms (21 nt) including a distinct monocot variant. Plant MIR408 family can be divided into six groups. miR408 majorly cleave genes belonging to blue copper protein in addition to several other species-specific targets in plants. Screening of 4726 rice accessions identified 22 sequence variants in 1 Kb upstream (15) and MIR408 region leading to the identification of 8 haplotypes (3: Japonica-specific and 5: Indica-specific). miR408-3p follows flag leaf preferential and drought upregulated expression profile in flag leaf and roots of N22 which seems to be regulated by differential fraction of mCs in the precursor region. The active pool of miR408 regulated targets under control and drought conditions is impacted by the tissue type. Comparative expression analysis of miR408/target module under different sets of conditions features 83 targets exhibiting antagonistic expression in rice. Twelve high confidence targets including 4 plantacyanins (OsUCL6, 7, 9 and 30), pirin, OsLPR1, OsCHUP1, OsDOF12, OsBGLU1, glycine rich cell wall, deoxyuridine 5-triphosphate nucleotidohydrolaseand OsERF7 with antagonistic expression under most conditions. Further, over-expression of osa-MIR408 in drought sensitive rice cultivar leads to the massive enhancement of vegetative growth in rice with improved ETR and Y(II) and enhanced the dehydration stress tolerance at seedling stage.

Mesothelin is a protein that is expressed in the mesothelial cell lining in the pleura, peritoneum and pericardium. The gene of mesothelin encodes a precursor protein that is processed to yield mesothelin, which is attached to the cell membrane by a glycophosphatidylinositol linkage and a shred fragment named the megakaryocytic-potentiating factor. The biological functions of this substance in normal cells are still unknown. Experimental studies on knockout mice suggest that this substance does not play an important role in development and reproduction. In contrast, it has been observed that mesothelin is produced in abnormal amounts in several malignant neoplasms such as mesotheliomas and pancreatic adenocarcinomas. Given that mesothelin is overexpressed in many solid tumours and has antigenic properties, this molecule could be considered a tumour marker or an antigenic target for many malignancies. Many molecular studies also have demonstrated that mesothelin is overexpressed in serous ovarian carcinomas and may bind to ovarian cancer antigen Ca-125, favouring the spread of the tumour in the abdominal cavity. Here, we discuss the current knowledge of mesothelin and focus on its role in clinical and pathological diagnoses as well as its impact on the prognosis in serous ovarian carcinomas. We also briefly discuss the latest progress of mesothelin-targeting therapies for this aggressive and lethal neoplasm.

MicroRNAs (miRNAs) are small and non-coding RNAs displaying aberrant expression in the tissue and plasma of cancer patients in comparison to healthy individuals. In past decades, accumulating data proposed that miRNAs could be diagnostic and prognostic biomarkers in cancer patients. It has been identified that miRNAs can act either as oncogenes through silencing of tumor inhibitors or tumor suppressor via targeting oncoproteins. MiR-144 is located in chromosomal region 17q11.2 that was widely destroyed in many types of cancers. Several studies revealed that miR-144 has different target genes including rapamycin, zonula occludens1, SFRP1, and ANO1. MiR-144 acts as a tumor suppressor or oncogene by targeting specific genes. In this review, we define the role of miR‐144 and its targets in different cancers and provide understanding in tumor proliferation, migration, and apoptosis.

Pristimerin (PM) is a naturally occurring quinonemethide triterpenoid compound that isolated from the Celastraceae and Hippocrateaceae families. Its anticancer effects have attracted a great deal of attention, but the mechanisms of action remain obscure. In this study, we screened for the active compounds of Pristimerin using a drug-likeness approach. Potential protein targets of Pristimerin were predicted by PharmMapper and Coremine database. Candidate protein targets were then uploaded to GeneMANIA and GO pathway analysis. Finally, compound-target, target-pathway, and compound-target-pathway networks were constructed using Cytoscape 3.3. The results showed that Pristimerin had good drug ability and identified 13 putative protein targets. Network analysis revealed that these targets are associated with cancer, inflammation and other physiological processes. In summary, Pristimerin is predicted to target a variety of proteins and pathways to form a network that exerts systemic pharmacological effects.

For effective warehouse management, various criteria should be taken into consideration in terms of inventory management, demand, transportation distance, usage area, delivery-waiting times, and minimizing the costs that may arise from them. Because, the purpose of the product assignment problem is to minimize the total transport distance during storage and to reduce the space required for product assignment. However, the storage location assignment problem (SLAP) occurs simultaneously with production planning activities in real life. In this study, an integrated mixed-integer nonlinear (MINLP) mathematical model is proposed, which includes the assignment of products to storage areas and production planning, using the TOPSIS (Technique for Order Preference by Similarity to Ideal Solution) class based policy for storage systems where multiple criteria are important. In the TOPSIS class-based policy, weight and waiting time criteria are taken into account, as well as the COI (Cube-per-order index index), which is widely used in the literature. In addition, a decision support system flow has been proposed that takes into account the single criterion, multiple criteria and COI index criteria of the developed model and provides its integration with different product assignment policies. Detailed literature research; It has been revealed that the proposed mathematical model and decision support system flow have the feature of applying an existing field of science to a new problem.

Balancing the efficiency and robustness of food systems is a well-known trade-off process. Over-optimization of efficiency may lead to excessive use of resources. On the other hand, under-optimization of efficiency may lead to excessive waste of resources. Using non-parametric methods can help in developing actionable frameworks through which decision-makers and stakeholders can effectively balance and improve food systems' efficiency and robustness. Under this context, this paper presents a new structured approach integrating two well-suited non-parametric methods for analyzing and balancing the interconnection between the efficiency and robustness of food systems. This approach consists of three main steps. First, the slacks-based data envelopment analysis (SBM-DEA) is utilized to analyze the efficiency of five food robustness dimensions. Second, the weighted efficiency of these dimensions is computed and analyzed to provide an insight into their influence on the food system efficiency. Finally, two search methods were developed to identify opportunities for improving efficiency and robustness. The outcomes of these methods have been analyzed and validated to ensure their effectiveness and viability. The operational and mathematical properties of the proposed approach were evaluated using data from thirty-seven food-producing countries. The weights of the robustness dimensions in this study were determined using the analytic hierarchy process (AHP) method. The input matrix of the AHP was constructed using expert judgment and consultations with stakeholders. The results of this study have shown an appropriate level of applicability and effectiveness of the proposed approach. While the first search method provided valuable insights, the second method proved to be more effective in identifying the sources of inefficacy of robustness dimensions. Several conclusions have been drawn and reported with some recommendations for future research works.

With the continuous increase in ship size combined with the generally slower increase in the size of waterways, the need for the prediction of ship maneuvering in shallow waterways continues to attract attention from the international scientific community. Ship behavior in shallow water is relevant in seabed effects that result in changing the hydrodynamic forces acting on the ship. In this study, the maneuvering characteristics of container ship with four degrees of freedom in shallow water are analyzed. The Reynolds-averaged Navier Stokes approach in Ansys Fluent code is used to produce the maneuvering coefficients through the simulations of forward running, static drift, static heel, circular motion, the combined motions, and the pure roll motion of the Kriso container ship. The maneuvering characteristics of the ship are estimated for evaluating the ship behaviors in shallow water condition. The obtained results show that the roll has a significant decrease and the ship’s turning diameter has a significant increase when the ship operates in the shallow waterway. The prediction of maneuvering characteristics of the ship are in good agreement with those of free running model tests, indicating that the numerical simulation based on the Computational Fluid Dynamics method has compromising capability to predict the maneuvering derivatives and the 4-DOF ship maneuvering motion in shallow water as well.

Since sensor-based perception systems are used in autonomous vehicle applications, validating such systems is imperative to guarantee the robustness of the systems before they are being put to use. In this study, a comprehensive corruption-related simulation-based robustness verification and enhancement process for sensor-based perception systems is proposed. Firstly, we present a methodology and scenario-based corruption generation tools for creating diverse simulated test scenarios that can analogously represent real-world traffic environments, especially considering corruption types related to safety concern. Then, an effective corruption similarity filtering algorithm is proposed to remove corruption types with high similarity and identify the representative corruption types to represent all considered corruption types. As a result, we can generate efficient corruption-related robustness test scenarios with less testing time and good scenario coverage. Subsequently, we perform the vulnerability analysis of object detection models to identify model weaknesses and construct an effective training dataset for model vulnerability enhancement. This enhances the tolerance of object detection models to weather and noise-related corruptions, ultimately improving the robustness of the perception system. We employ case studies to demonstrate the feasibility and effectiveness of the proposed robustness verification and enhancement procedures. Additionally, we explore the impact of different "similarity overlap threshold" parameter settings on scenario coverage, effectiveness, scenario complexity (size of training and testing datasets), and time costs.

Bistatic scattering coefficient have important application of ocean active microwave remote sensing. In this paper, a general expression of the composite scattering coefficient for multiple dielectric targets of one-dimensional fractal sea surface is derived by MOM method. Secondly, the bistatic scattering coefficient is computed, there are two class missile targets and one class ship target of one-dimensional fractal sea surface, and the influence of the water dielectric constant, fractal dimension, wind speed, the target dielectric constant and spatial position is discussed, and the corresponding conclusions are given. The proposed algorithm is able to solve some composite scattering problems, such as “dielectric or conductive object + rough surface”, “dielectric or conductive floating object +rough ”and it has certain generalization and reference.

Compared to wide-field telescopes, small-field detection systems have higher spatial resolution, resulting in stronger detection capabilities and higher positioning accuracy. When detecting by small-field in synchronous orbit, both space debris and fixed stars are imaged as point targets, making it difficult to distinguish them. In addition, with the improvement of detection capabilities, the number of stars in the background rapidly increases, which puts higher requirements on recognition algorithms. Therefore, star detection is indispensable for identifying and locating space debris in complex backgrounds. To address these difficulties, this paper proposes a real-time star extraction method based on adaptive filtering and multi frame projection. We use bad point repair and background suppression algorithms to preprocess star image. Afterwards, we analyze and enhance the target signal-to-noise ratio(SNR). Then, we use multi frame projection to fuse information. Subsequently, adaptive filtering, adaptive morphology, and adaptive median filtering algorithms are proposed to detect trajectories. Finally, the projection is released to locate the target. Our recognition algorithm has been verified by real star images, and the images were captured using small-field telescope. The experimental results demonstrate the effectiveness of the algorithm proposed in this paper. We successfully extracted hip-27066 star, which has magnitudes about 12 and SNR about 1.5. Compared with existing methods, our algorithm has advantages in both recognition rate and false-alarm rate, and can be used as real time target recognition algorithm for space-based synchronous orbit detection payload.

Although natural products are an important source of drugs and drug leads, identification and validation of their target proteins have proven difficult. Here, we report the development of a systematic strategy for target identification and validation employing drug affinity responsive target stability (DARTS) and mass spectrometry imaging (MSI) without modifying or labeling natural compounds. Through a validation step using curcumin, which targets aminopeptidase N (APN), we successfully standardized the systematic strategy. Using label-free voacangine, an antiangiogenic alkaloid molecule as the model natural compound, DARTS analysis revealed vascular endothelial growth factor receptor 2 (VEGFR2) as a target protein. Voacangine inhibits VEGFR2 kinase activity and its downstream signaling by binding to the kinase domain of VEGFR2, as was revealed by docking simulation. Through cell culture assays, voacangine was found to inhibit the growth of glioblastoma cells expressing high levels of VEGFR2. Specific localization of voacangine to tumor compartments in a glioblastoma xenograft mouse was revealed by MSI analysis. The overlap of histological images with the MSI signals for voacangine was intense in the tumor regions and showed colocalization of voacangine and VEGFR2 in the tumor tissues by immunofluorescence analysis of VEGFR2. The strategy employing DARTS and MSI to identify and validate the targets of a natural compound as demonstrated for voacangine in this study is expected to streamline the general approach of drug discovery and validation using other biomolecules including natural products.

This study proposes a novel hybrid machine learning approach for modeling of rainfall-induced shallow landslides. The proposed approach is a combination of an instance-based learning algorithm (k-NN) and Rotation Forest (RF), state of the art machine techniques that have seldom explored for landslide modeling. The Lang Son city area (Vietnam) is selected as a case study. For this purpose, a spatial database for the study area was constructed, and then, was used to build and evaluate the hybrid model. Performance of the model was assessed using Receiver Operating Characteristic (ROC), area under the ROC curve (AUC), success rate and prediction rate, and several statistical evaluation metrics. The results showed that the model has high performance with both the training data (AUC = 0.948) and the validation data (AUC = 0.848). The results were compared with those obtained from soft computing techniques i.e. Random Forest, J48 Decision Trees, and Multilayer Perceptron Neural Networks. Overall, the performance of the proposed model is better than those obtained from the above methods. Therefore, the proposed model is a promising tool for landslide modeling. The research result can be highly useful for land use planning and management in landslide prone areas.

The worldwide population is undergoing a fundamental change in its age structure, which challenges the health and social services system. The need to migrate towards a more person-centered and coordinated model of care that supports the optimization of abilities and capacities for older people has to be matched. In this sense, eHealth technologies can play a fundamental role. In this paper, through a questionnaire-based data collection on 30 primary (older people) and 32 secondary (informal caregivers) end-users, we share the sustainable way to develop a product optimizing the user experience and ensuring adoption. Both older adults and caregivers consider the use of smartphone and smartwatch to be very important, but also the use of digital devices for healthcare can be helpful. Seniors care about self-monitoring of health parameters using wearable devices, regardless of their health status, and would like to be included in the process of making good health decisions, because they need to feel in control of their healthcare process. Digital solutions in health and care can support the wellbeing of older adults in many areas of their daily lives at home and in their communities, but only if such innovation is designed around the natural voice of the intended target.

Acute low back pain (LBP) stands as a leading cause of activity limitation and work absenteeism, and its associated healthcare expenditures are expected to become substantial when acute LBP develops into a chronic and even refractory condition. Therefore, early intervention is crucial to prevent progression to chronic pain whose management is particularly challenging and for which the most effective pharmacological therapy is still controversial. Current guideline treatment recommendations vary and are mostly driven by expertise with opinion differing across different interventions. Thus, it is difficult to formulate evidence-based guidance when relatively few randomized clinical trials did explore the diagnosis and management of LBP while employing different selection criteria, statistical analyses, and outcome measurements. This narrative review aims to provide a critical appraisal of current acute LBP management by discussing the unmet needs and areas of improvement from bench-to-bedside and proposes multimodal analgesia as the way forward to attain an effective and prolonged pain relief and functional recovery in patients with acute LBP.

Physiologically Based Pharmacokinetic Models (PBPK) are mechanistical tools generally employed in the pharmaceutical industry and environmental health risk assessment. These models are recognised by regulatory authorities for predicting organ concentration-time profile, pharmacokinetic and daily intake dose of xenobiotics. Extension of PBPK models to capture sensitive populations like pediatric, geriatric, pregnant females, fetus etc. and diseased population like renal impairment, liver cirrhosis etc. is a must. However, the current modelling practice and existing models are not mature enough to confidently predict the risk in these populations. A multidisciplinary collaboration between clinicians, experimental and modeler scientist is vital to improve the physiology, and calculation of biochemical parameters for integrating the knowledge and refining existing PBPK models. Specific PBPK covering compartments like cerebrospinal fluid, and hippocampus are required to gain mechanistic understanding about xenobiotic disposition in these sub-parts. The PBPK model assists in building quantitative adverse outcome pathways (qAOPs) for several endpoints like developmental neurotoxicity (DNT), hepatotoxicity and cardiotoxicity. Machine learning algorithms can predict physicochemical parameters required to develop in-silico models where experimental data is unavailable. Integrating machine learning with PBPK carries the potential to revolutionize the field of drug discovery and development and environmental risk. Overall, this review tried to summarize the recent developments in the in-silico models, building qAOPs, use of machine learning for improving existing models along with a regulatory perspective. This review can act as a guide for toxicologists who wish to build their careers in kinetic modeling.

In recent years, demand has been increasing for target detection and tracking from aerial imagery via drones using onboard powered sensors and devices. We propose a very effective method for this application based on a deep learning framework. A state-of-art embedded hardware system empowers small flying robots to carry out the real-time onboard computation necessary for object tracking. Two types of embedded modules were developed: one is designed using a Jetson TX or AGX Xavier, and the other is based on an Intel Neural Compute Stick. These are suitable for real-time onboard computing power on small flying drones with limited space. A comparative analysis of current state-of-art deep-learning-based multi-object detection algorithms was carried out utilizing the designated GPU-based embedded computing modules to obtain detailed metric data about frame rates as well as the computation power. We also introduce an effective target tracking approach for moving objects. The algorithm for tracking moving objects is based on the extension of simple online and real-time tracking. It was developed by integrating a deep-learning-based association metric approach (Deep SORT), which uses a hypothesis tracking methodology with Kalman filtering and a deep-learning-based association metric. In addition, a guidance system that tracks the target position using a GPU-based algorithm is introduced. Finally, we demonstrate the effectiveness of the proposed algorithms by real-time experiments with a small multi-rotor drone.

In the past few years, cloud-based additive manufacturing has shown its application and potential in industries. For this reason, when the demand for cloud-based additive products increases, efficient scheduling of related tasks becomes more important to achieve optimized duration. This research proposes a Heuristic Scheduling Algorithm (HSA) for use in Cloud-Based Additive Manufacturing (CBAM) with an approach to Critical Chain Buffer Management (CC/BM). This research aims to schedule and optimize the time in cloud-based additive manufacturing, in addition to the parts production process, it also includes the steps of receiving online orders and informing the manufacturing unit and sending them to the customer. The HSA proposed in this research consists of three phases 1- Buffer sizing, 2- Additive manufacturing and logistics scheduling, and 3- Buffer controlling. To evaluate, the performance of the algorithm is simulated. The finding shows that the proposed HAS can effectively solve the CBAM scheduling problem.

In the industrial field, the 3D target detection algorithm PointPillars has gained popularity. Improving target detection accuracy while maintaining high efficiency has been a significant challenge. To address the issue of low target detection accuracy in the PointPillars 3D target detection algorithm, this paper proposes an algorithm based on feature enhancement to improve the backbone network. The algorithm enhances preliminary feature information of the Backbone network by modifying it based on PointPillars with the aid of channel attention and spatial attention mechanisms. To address the inefficiency caused by the excessive number of subsampled parameters in PointPillars, FasterNet (a lightweight and efficient feature extraction network) is utilized for downsampling and forming different scale feature maps. To prevent the loss and blurring of extracted features resulting from the use of inverse convolution, we utilize the lightweight and efficient up-sampling modules Carafe and Dysample for adjusting resolution. Experimental results indicate improved accuracy under all difficulties of the KITTI dataset, demonstrating the superiority of the algorithm over PointPillars.

Pancreatic cancer leads the most common lethal tumor in America. This lethality is related to limited treatment options. Conventional treatments involve a non-specific use of chemotherapeutical agents like 5-FU, capecitabine, gemcitabine, cisplatine, oxaliplatine, or irinotecan, that produce several side effects. This review we focus on the use of targeted nanoparticles as an alternative to the standard treatment for the pancreatic cancer. The principal objective of the use of nanoparticles is the reduction in side effects that conventional treatments produce, mostly because of their nonspecificity. Currently, several molecular markets of pancreatic cancer cells have been studied to target nanoparticles and improve the actual treatment. Therefore, properly functionalizated nanoparticles with specific aptamers or antibodies can be used to recognize pancreatic cancer cells and once cancer is recognized, these nanoparticles can attack the tumor by drug delivery, hyperthermia, or gene therapy.

Amyotrophic Lateral Sclerosis (ALS) is a prototypical neurodegenerative disease characterized by progressive degeneration of motor neurons to severely effect the functionality to control voluntary muscle movement. Most of the non additive genetic aberrations responsible for ALS make its molecular classification very challenging along with limited sample size, curse of dimensionality, class imbalance and noise in the data. Deep learning methods have been successful in many other related areas but have low minority class accuracy and suffer from the lack of explainailbilty when used directly with RNA expression features for ALS molecular classification. In this paper we propose a deep learning based molecular ALS classification and interpretation framework. Our framework is based on training a convolution neural network (CNN) on images obtained from converting RNA expression values into pixels based on DeepInsight similarity technique. Then we employed Shapley Additive Explanations (SHAP) to extract pixels with higher relevance to ALS classifications. These pixels were mapped back to the genes which made them up. This enabled us to classify ALS samples with high accuracy for a minority class along with identifying genes that might be playing an important role in ALS molecular classifications. Taken together with RNA expression images classified with CNN, our preliminary analysis of the genes identified by SHAP interpretation demonstrate the value of utilising Machine Learning to perform molecular classification of ALS and uncover disease-associated genes.

Nanoscale imaging with the ability to identify cellular organelles and protein complexes has been a highly challenging subject in secondary ion mass spectrometry (SIMS) of biological samples. This is because only a few isotopic tags can be used successfully to target specific proteins or organelles. To address this, we have generated gold-nanoprobes, in which gold nanoparticles are conjugated to nanobodies. The nanoprobes were well suited for specific molecular imaging using NanoSIMS at subcellular resolution. They demonstrated to be highly selective to different proteins of interest, and sufficiently sensitive for SIMS detection. The nanoprobes offer the possibility of correlating the investigation of cellular isotopic turnover to the positions of specific proteins and organelles, thereby enabling an understanding of functional and structural relations that are currently obscure.

In order to meet the national energy saving goals set in the Vietnam National Energy Efficiency Program in the period of 2019 – 2030 (VNEEP), the Vietnamese government has adopted a series solutions and policies to improve energy efficiency. The Vietnam’s 63 provinces will be as main actor for the national achievement in energy efficiency. Thus, understanding the province’s potentiality of energy efficiency is useful for the harmonious and sustainable development between the economy and energy systems. In this study, provincial and national data from General Statistic Office are analyzed in terms of the energy efficiency levels. With the trends of economic development and energy consumption in both national and regional levels, the Lorenz curve between Vietnamese energy consumption and GDP is investigated. The Lorenz coefficient shows the energy allocation is nether reasonable nor balanced. By using clustering method, the 63 provinces of Vietnam clustered into 7 groups that the provinces in the cluster has the similar indexes of energy efficiency i.e. ability, responsibility, potential and difficulty. The energy consumption and GDP are predicted in the period of 2019 – 2025. Based on the difference of GDP development and energy consumption levels, the target of energy efficiency for each province through clustering is set. The results show that 33 provinces included in the cluster 1, 2, 3, 4 and 6 are heavy contribution. Among them, the provinces in the cluster 2 and 3 need to focus on the industry sector in their energy saving policy. The cluster 7 included the under-developed provinces can learn development’s experiences of the provinces in the cluster 1, 2, 3 and 4 to find the best way of their future development.

The emotional dimension in education has become increasingly important in recent decades. Enhancing the emotional dimension of prospective teachers in science subjects is higher education stuff responsibility. The implementation of active methodologies could modify the traditional student-teacher roles that are encouraged by the educational policies implemented in the Bologna Process. The principal aim of this work is to describe a Project Based Learning methodology and to introduce it as potential resource for the emotional and cognitive improvement of 19 prospective primary teachers enrolled in a scientific subject. This is a qualitative study with a transversal sustainability approach in the context of a research line focused on Higher Education for Sustainable Development. A questionnaire was designed and filled by the students at two different times, before and after implementation of the activity. The initial feedback from students was surprisingly enthusiastic by the fact that they were working with rockets, despite of this is not a common emotion in the science field. The results show the emotional improvement of prospective teachers after the implementation. It is concluded that a correct science education is necessary during the training of teachers taking into account their emotional dimension and the social repercussion due to the future transmission.

Cellular agriculture is defined as the production of agricultural products from cell cultures rather than from whole plants or animals. With growing interest in cellular agriculture as a means to address the public health, environmental, and animal welfare challenges of animal agriculture, the concept of producing seafood from fish cell- and tissue-cultures is emerging as a means to address similar challenges with industrial aquaculture systems and marine capture. Cell-based seafood - as opposed to animal-based seafood - can combine developments in biomedical engineering with modern aquaculture techniques. Biomedical engineering developments such as closed-system bioreactor production of land animal cells create a basis for large scale production of marine animal cells. Aquaculture techniques such as genetic modification and closed system aquaculture have achieved marked gains in production that can pave the way for innovations in cell-based seafood production. Here, we present the current state of innovation relevant to the development of cell-based seafood across multiple species as well as specific opportunities and challenges that exist for advancing this science. The authors find that the physiological properties of fish cell- and tissue- culture may be uniquely suited to cultivation in vitro. These physiological properties, including hypoxia tolerance, high buffering capacity, and low-temperature growth conditions, make marine cell culture an attractive opportunity for scale production of cell-based seafood; perhaps even more so than mammalian and avian cell cultures for cell-based meats. This, coupled with the unique capabilities of crustacean tissue-friendly scaffolding such as chitosan, a common seafood waste product and mushroom derivative, presents great promise for cell-based seafood production via bioreactor cultivation. To become fully realized, cell-based seafood research will require more understanding of fish muscle culture and cultivation; more investigation into serum-free media formulations optimized for fish cell culture; and bioreactor designs tuned to the needs of fish cells for large scale production.

A claim management office (CMO) is a new intra-organisation fit based on an organisational project management (OPM) approach and deals specifically with improving claim performance. However, CMO is either misunderstood or often overlooked in construction companies, mainly due to ignorance of the OPM context but further exacerbated by a lack of real case study research on how to adopt CMO in these organisations. This study addresses this prevailing knowledge gap by investigating the nature of the construction industry from the CMO viewpoint and developing an extensive framework through which to improve organisational claims performance. Organisational ambidexterity theory integrated with X-inefficiency theory is adopted for claims performance outcomes, due to organisation intra-firm irrational decisions when managing such claims. Data was obtained and analysed from a international large construction company (which used CMOs) and its internal focus group discussion (as a multi-method approach). The reference framework provides new perspectives on how construction-related companies can adopt a CMO structure, which enables them to improve claims performance by planning in three interrelated activities viz. function-, process- and performance-based-. Furthermore, findings contribute to researchers and practitioners by providing a true understanding of the CMO-related mechanism and plausible roadmap for future work.

Manipulating autophagy is a promising strategy for treating cancer as several autophagy inhibitors shown to induce autophagic cell death. One of these, autophagonizer (APZ), induces apoptosis-independent cell death by binding an unknown target via an unknown mechanism. To identify APZ targets we used a label-free drug affinity responsive target stability (DARTS) approach with a liquid chromatography/tandem mass spectrometry (LC-MS/MS) readout. Of 35 protein interactors, we identified Hsp70 as a key target protein of unmodified APZ in autophagy. Either APZ treatment or Hsp70 inhibition attenuates integrity of lysosomes, which leads to autophagic cell death exhibiting an excellent synergism with a clinical drug, temozolomide, in vitro, in vivo, and orthotropic glioma xenograft model. These findings demonstrate the potential of APZ to induce autophagic cell death and its development to combinational chemotherapeutic agent for glioma treatment. Collectively, our study demonstrated that APZ, a new autophagy inhibitor, can be used as a potent antitumor drug candidate to get over unassailable glioma and revealed a novel function of Hsp70 in lysosomal integrity regulation of autophagy.

The COVID-19 pandemic has posed a significant global threat, leading to several initiatives for its control and management. One such initiative involves wastewater-based epidemiology, which has gained attention for its potential to provide early warning of virus outbreaks and real-time information on its spread. In this study, water samples from two wastewater treatment plants (WWTPs) located at the south east of Spain (Region of Murcia) namely Murcia, and Cartagena, were analyzed by RT-qPCR, Phylogenetic Analysis, and Machine Learning Approach. The aim was to determine whether SARS-CoV-2 detection in the WWTPs of these two cities could serve as a proxy for the virus's spread in the population. The results confirmed that the levels of SARS-CoV-2 in these wastewater samples changed concerning the number of SARS-CoV-2 cases detected in the population and variant occurrences were in line with clinical reported data. Additionally, the phylogenetic analysis showed that samples obtained in close sampling times exhibited a higher similarity than those obtained more distantly in time. A second analysis using a machine learning approach based on the mutations found in the SARS-CoV-2 spike protein was also conducted. Hierarchical Clustering (HC) was used as an efficient unsupervised approach for data analysis. Results indicated that samples obtained in October 2022 in Murcia and Cartagena were significantly different, which corresponded well with the different virus variants circulating in the two locations. The proposed methods in this study are adequate for comparing the Accumulated Natural Vector (ANV) of the SARS-CoV-2 sequences as a preliminary evaluation of potential changes in the variants that are circulating in a given population at a specific time point.

Virus-infected Flu is a common disease. To date, no specific drugs are available to manage the symptoms of cough, headache and sputum production. An alternative Chinese herb medicine is introduced for virus-infected Flu or similar infection. Before hospitalization, some of patients may scare for cross-infection with mild symptoms or hardly go to hospital if encountered a temporary lockdown or quarantine. Some Chinese practice self-treatment of cough, headache and sputum production by inhalation of volatile chemicals from onion and garlic. Author used to take the same alternative approach of inhalation of onion, garlic or scallions for self-treatment when suffered virus caused flu with cough, headache and sputum production at onset disease. In this article, the biomedical effects of onion and garlic are reviewed. To help patients with mild symptoms of virus infected Flu, a simple home-based treatment was suggested to self-treatment because of temporary isolation and hardly going to hospitalization. The alternative approach may also suggest for some mild virus infected respiratory diseases caused by virus at onset disease.

WHO reported an estimated 249 million malaria cases and 608,000 malaria deaths in 85 countries in 2022. A total of 94% of malaria deaths occurred in Africa, 80 % of which were children under 5. In other words, one child dies every minute from malaria. The RTS,S/AS01 malaria vaccine, that uses the Plasmodium falciparum circumsporozoite protein (CSP) to target sporozoite infection of the liver, achieved modest efficacy. The Malaria Vaccine Implementation Program (MVIP), coordinated by the WHO and completed at the end of 2023, found that immunization reduced mortality by only 13%. To further reduce malaria death, development of a more effective malaria vaccine is a high priority. Three major malaria vaccine targets being considered are the level of sporozoite liver infection, merozoite red blood cell (RBC) infection, and mosquito midgut infection. These targets involve specific ligand-receptor interactions. However, current malaria vaccine candidates that target two major parasite population bottlenecks, liver infection and mosquito midgut infection, do not focus on such parasite ligands. Here we evaluate the potential of newly identified parasite ligands as novel malaria vaccine antigens.

Tumor heterogeneity is a major obstacle in cancer therapy. We offer a novel perspective on tumor heterogeneity, informed by expanding upon the current view on tumor evolution. It is commonly known that in cancer, it is the advantageous genes and mutations that drive tumor capacities and the progression. We recognize an earlier, often overlooked, but necessary thus crucial step preceding the activation of advantageous genes functionality, namely, cellular response. We suggest that cancer is driven by an adaptive action taken by any organism when confronted with adversity - a cellular response to generate specific cancer capacities demanded to overcome survival threat - the responses that prompt the utilization of the functionality of advantageous genetic mutations and genes to attain these capacities and drive the disease. The ongoing development of cancer capabilities, as cells endeavor to obtain a competitive advantage, results in increased molecular chaos, observed as tumor heterogeneity. When the evolutionary drive for survival is impeded by therapeutic inhibition of critical genes, cell death occurs, a phenomenon thus termed oncogene addiction. We summarize the implications of this new framework for understanding tumor evolution and anti-cancer drug discovery, as well as understanding of basic cancer biology.

Abstract: Rationale. Object tracking has significance in many applications ranging from control of unmanned vehicles to autonomous monitoring of specific situations and events, especially when providing safety for patients with certain adverse conditions such as epileptic seizures. Conventional tracking methods face many challenges, such as the need for dedicated attached devices or tags, influence by high image noise, complex object movements, and intensive com-putational requirements. We have developed earlier computationally efficient algorithms for global optical flow reconstruction of group velocities that provide means for convulsive seizure detection and have potential applications in fall and apnea detection. Here, we address the chal-lenge of using the same calculated group velocities for object tracking in parallel. Methods. We propose a novel optical flow-based method for object tracking. It utilizes real-time image se-quences from the camera and directly reconstructs global motion-group parameters of the con-tent. These parameters can steer a rectangular region of interest surrounding the moving object to follow the target. The method successfully applies to multi-spectral data, further improving its effectiveness. Results. Experimental results on simulated tests and complex real-world data demonstrate the method's capabilities. The proposed optical flow reconstruction can provide accurate, robust, and faster results compared to current state-of-the-art approaches.

This article utilizes the Canny edge extraction algorithm based on contour curvature and the cross-correlation template matching algorithm to extensively study the impact of high-repetition-rate CO2 pulsed Laser on the target extraction and tracking performance of the infrared imaging detector. It establishes a quantified dazzling pattern for lasers on infrared imaging systems. By conducting laser dazzling and damage experiments, a detailed analysis of the normalized correlation between target and dazzling images is performed to quantitatively describe laser dazzling effects. Simultaneously, an evaluation system, including target distance and laser power evaluation factors, is established to determine the dazzling level and whether the target is recognizable. The research results reveal that laser power and target position are crucial factors affecting the detection performance of infrared imaging-guided weapon systems under laser dazzling. Different laser powers are required to successfully interfere with the recognition algorithm of infrared imaging-guided weapons at different distances. And laser dazzling will produce a lot of false edge information, which seriously affects the performance of pattern recognition algorithm. In laser damage experiments, the detector experienced functional damage, with a quarter of the image displaying as completely black. The energy density threshold required for functional damage to the detector is approximately 3 J/cm2. The dazzling assessment conclusions also apply to evaluating damage results. Finally, the proposed evaluation formula aligns with experimental results, objectively reflecting the actual impact of laser dazzling on the target extraction and tracking performance of infrared imaging systems. This study provides an in-depth and accurate analysis for understanding the influence of lasers on the performance of infrared imaging-guided weapons.

Background: Chronic Myeloid Leukemia (CML) is initiated in bone marrow due to chromosomal translocation t(22;9) leading to fusion oncogene BCR-ABL. Targeting BCR-ABL by tyrosine kinase inhibitors (TKI) have changed fatal CML into an almost curable disease. Despite that, TKIs lose their effectiveness due to disease progression. Unfortunately, mechanism of CML progression is poorly understood and common biomarkers for CML progression are unavailable. This study was conducted to find out novel biomarkers of CML progression by employing whole exome sequencing (WES).Materials and Methods: WES of accelerated phase (AP-) and blast crisis (BC-) CML patients was carried out, with chronic phase CML (CP-CML) patients as control. After DNA library preparation and exome enrichment, clustering and sequencing was carried out using Illumina platforms. Statistical analysis was carried out using [SAS/STAT] software version 9.4 and R package employed to find mutations shared exclusively by all AP-/BC-CML. Confirmation of mutations was carried out using Sanger sequencing and protein structure modelling using I-Tasser followed by mutant generation and visualization using PyMOL. Results: Three novel genes (ANKRD36, ANKRD36B and PRSS3) were mutated exclusively in all AP-/BC-CML patients. Only ANKRD36 gene mutations (c.1183_1184 delGC and c.1187_1185 dupTT) were confirmed by Sanger sequencing. Protein modelling studies showed that mutations induce structural changes in ANKRD36 protein. Conclusions: Our studies show that ANKRD36 is a potential common biomarker and drug target of early CML progression. ANKRD36 is yet uncharacterized in human. It has the highest expression in bone marrow, specifically myeloid cells. We recommend carrying out further studies to explore the role of ANKRD36 in biology and progression of CML.

Biofilm-associated proteins (BAPs) are important in the development and resilience of biofilms, which are intricate populations of microbes protected by extracellular matrix. All members of the BAP family are known to possess common characteristics such as high molecular weight and a signal sequence for extracellular secretion. It has been shown that BAPs are directly linked to the pathogenicity of many bacteria. This mini review highlights several potential strategies to target BAPs for drug development.

The microbiome is pivotal in maintaining health and influencing disease by modulating essential inflammatory and immune responses. Hepatocellular carcinoma (HCC), ranking as the third most common cause of cancer-related fatalities globally, is influenced by the gut microbiome through bidirectional interactions between the gut and liver, as evidenced in both mouse models and human studies. Consequently, biomarkers based on gut microbiota represent promising non-invasive tools for the early detection of HCC. There is a growing body of evidence suggesting that the composition of the gut microbiota may play a role in the efficacy of immunotherapy in different types of cancer, thus it could be used as a predictive biomarker. In this review, we will dissect the gut microbiome's role as a potential predictive and diagnostic marker in HCC and evaluate the latest progress in leveraging the gut microbiome as a novel therapeutic avenue for HCC patients, with a special emphasis on immunotherapy.

Owing to the upsurge in the number of endangered species and understanding animal patterns in general as well as population demographics; the monitoring of wildlife species is an essential for the conservation and safety of animals. In order to organize and manage the reserves, the nature bequeaths to us, we need to have hands-on information of their population and food trends, conditions where they survive and other species in the ecosystem. The paper presents a vision-based approach to monitor wildlife using an aerial platform. A quad-rotor based aerial platform is used for the very first time for this purpose. Field imaging is done using a digital cellphone camera mounted on the platform to acquire video of horses in the field. Two techniques, Lucas-Kanade and Horn-Schunck methods are applied on the acquired set of images and the results are compared. Noise due to fluctuations and light conditions are minimized using Gaussian and HSV filters. Experiments show results with an absolute mean difference of 2.84 pixels and 8.50 pixels for changes in X and Y directions respectively for the two approaches.

The aim of this study is to analyse problems related to thermal mapping obtained from thermal data acquired from Unmanned Aerial Systems (UAS) equipped with thermal cameras. We focused on an accurate analysis of uncertainties introduced by the PIX4D Mapper software used to obtain the surface temperature maps of thermal images acquired by the UAS. To achieve this aim, we used artificial thermal reference during the surveys, as well as natural hot targets, i.e. thermal anomalies in the Pisciarelli hydrothermal system in Campi Flegrei caldera (CFc). Artificial thermal targets, expressly created and designed for this goal, are a prototype here called “developed thermal target” (DTT) made by the drone Laboratory at Istituto Nazionale di Geofisica e Vulcanologia - Osservatorio Vesuviano (INGV-OV). We show the results obtained by three surveys during which thermal targets were positioned on land at different flight heights of the UAS. Different heights were also necessary to test spatial resolution of the DTT with the used thermal camera as well as possible temperature differences between the raw images acquired by UAS with the thermal mapping obtained from the PIX4D Mapper software. In this work we have estimated the uncertainty that may be introduced by the mosaic procedure and furthermore we find an attenuation of the measured temperatures introduced by the different distances between the thermal anomaly and sensor. These results appear to be of great importance for the subsequent calibration phase of the thermal maps especially in cases where these methodologies are applied for monitoring purposes of volcanic/geothermal areas.

Buffalo are silent breeders, therefore detecting estrus is a serious challenge. There is a rising need for sensitive and precise biomarkers in this scenario. Recent research on miRNA has demon-strated the importance of these molecules as biomarkers. Though there have been miRNA studies in saliva during the estrous cycle, there have been few miRNA research in blood samples. The current study was designed to look at blood miRNAs during the oestrous cycle in heifers (n=5) to address the issue of silent estrus. On the day of estrus and diestrus, blood samples from 60 heifers were obtained and pooled into (n=5) separate samples. Ultrasonography and progesterone assay was performed to confirm estrus. Then, employing particular miRNA adapters, small RNA se-quencing of miRNA was performed using the Illumina Miseq 2500. The UEA sRNA bioinfor-matics workbench identified 94 substantially differently expressed miRNAs (p>0.05) from these data. In estrus, 63 miRNA were upregulated and 31 miRNA were downregulated. When fold change was increased to (log2foldchange >1; q value less than 0.05), 25 miRNAs were elevated during estrus. miR-497, miR-582, miR-10174, miR-23, miR-223, miR-1296 were upregulated, whereas miR-10167, 671, 1246,122 were downregulated. miR-497 is unusually elevated (log2 foldchange>5) when compared to another miRNA (log2 foldchange >5) miRNet 2.0, Cytoscape, and MIENTURNET network software found that miR-497 has more degree centrality, above 60; it is associated with more than 60 nodes, followed by miR-93

When ground-penetrating radar is used to detect targets within concrete, the location of the targets, the identification of different shapes, properties and less obvious echoes all greatly increase the interpretation time of the staff and can easily cause misjudgment of the echo images. In this paper, the ground-penetrating radar echo images (B-scan) after processing are mean filtered to eliminate the direct waves that interfere greatly with the echoes. The RFB-s structure is added to the YOLOv3-SPP network structure, while the Anchor value is optimized and the EIOU loss function is introduced. For four types of data with different shapes and properties at random target locations, three models, YOLOv3, YOLOv3-SPP and the improved YOLOv3-SPP, are used for classification and identification, and the proposed algorithm models are comprehensively evaluated using model evaluation metrics. The experimental results show that the algorithm models proposed in this paper have good recognition effect in ground-penetrating radar echo image target detection.

Alfalfa primarily produces seeds through cross-pollination among different individuals. Self-pollination results in severe inbreeding depression, such as weak seedlings and termination of growth. Identifying the genetic loci associated with vigorous plant growth could enable the elimination of deleterious alleles and eventually develop inbred alfalfa lines for hybrid production. In this study, 215 alfalfa accessions were self-pollinated for three generations. Within accessions, pairs of weak and strong plants were sampled and bulked for exome sequencing. We extracted individual DNA from 534 plants that included parental clones, strong and weak pairs of plants, and plants selected based on the number of seeds produced. Among them, we formed 42 pools, including 16 with strong plants and 17 with weak plants, 3 top-seeded plants, 3 low-seeded plants, and 3 no-seeded plants. Along with 79 individuals, these pools were sequenced in the target regions covering 112,626 contigs across the entire alfalfa genome. From the 121 samples, (42+79) genotyped, 13.2 million SNPs including indels were generated. After filtering for MAF (>5%), depth (<20X), and no missing genotype and removing indels, a total of 588,136 SNPs were obtained which were used for final analysis. A genome-wide association study was performed and identified 11 genetic loci associated with alfalfa plant growth vigor. The GO analysis generated 12 significantly enriched GO terms. The associated SNPs were on, and near genes involved in stress response, defense responses against pathogens, and plant reproduction. These identified SNPs benefit the development of alfalfa inbred lines by purging the deleterious alleles and biomass improvement through marker-assisted selection.

Traditional camera sensors rely on human eyes for observation. However, the human eye 1 is prone to fatigue when observing targets of different sizes for a long time in complex scenes, and 2 human cognition is limited, which often leads to judgment errors and greatly reduces the efficiency. 3 Target recognition technology is an important technology to judge the target category in camera 4 sensor. In order to solve this problem, a small size target detection algorithm for special scenarios was 5 proposed by this paper. Its advantage is that this algorithm not only has higher precision for small 6 size target detection, but also can ensure that the detection accuracy of each size is not lower than the 7 existing algorithm. In this paper, a new down-sampling method was proposed, which could better 8 preserve the context feature information. The feature fusion network was improved to effectively 9 combine shallow information and deep information. A new network structure was proposed to 10 effectively improve the detection accuracy of the model. In terms of accuracy, it is better than: YOLOX, 11 YOLOXR, YOLOv3, scaled YOLOv5, YOLOv7-Tiny and YOLOv8.Three authoritative public data sets 12 were used in this experiment: a) On Visdron data sets (small size targets), DC-YOLOv8 is 2.5% more 13 accurate than YOLOv8. b) On Tinyperson data sets (minimal size targets), DC-YOLOv8 is 1% more 14 accurate than YOLOv8. c) On PASCAL VOC2007 data sets (Normal size target), DC-YOLOv8 is 0.5% 15 more accurate than YOLOv8.

MicroRNAs (miRNAs) are small non-coding RNAs that play a central role in the post-transcriptional regulation of biological processes. miRNAs regulate transcripts by direct binding involving the Argonaute protein family. The exact rules of binding are not known, and several in silico miRNA target prediction methods have been developed to date. Deep Learning has recently revolutionized miRNA target prediction. However, the higher predictive power comes with decreased ability to interpret increasingly complex models. Here, we present a novel interpretation technique, called attribution sequence alignment, for miRNA target site prediction models that can interpret such Deep Learning models on a two-dimensional representation of miRNA and putative target sequence. Our method produces a human readable visual representation of miRNA:target interactions and can be used as a proxy for further interpretation of biological concepts learned by the neural network. We demonstrate applications of this method in clustering of experimental data into binding classes, as well as using the method to narrow down predicted miRNA binding sites on long transcript sequences. Importantly, the presented method works with any neural network model trained on a two-dimensional representation of interactions and can be easily extended to further domains such as protein-protein interactions.

Global crop yields are estimated to be reduced by 30–40% per year on account of plant pests and pathogens. Agricultural insect pests raise concerns about constraining global food security and climate changes contributing to the rise of infestation. The current management relies on plant breeding, associated or not with transgenes and chemical pesticides. Both approaches face serious technology obsolescence on the field due to resistance breakdown or development of insecticide resistance. The need for new Modes of Action (MoA) approaches in managing crop health grows each year, driven by market demands to reduce economic losses and phytosanitary requirements to meet the consumer perception. Disabling pest genes by sequence-specific expression silencing is considered a promising tool in the development of environment and health respectful biopesticides. The specificity conferred by long dsRNA-base solutions give support to minimizing effects on off-targeted genes in the insect pest genome and the target gene in non-target organisms (NTOs). In this review, we summarize the current status of gene silencing by RNA interference (RNAi) for agricultural control. More specifically, we focus on the engineering, development and application of gene silencing to control Lepidoptera by the employment of non-transforming dsRNA technologies. Despite some delivery and stability drawbacks of topical applications, we reviewed works showing convincing proof-of-concept results that point to imminent innovative solutions. Considerations about the regulamentation of the ongoing research on dsRNA-based pesticides to produce commercialized products for exogenous application are discussed. Academic and industry initiatives reveal a worthy effort to accomplish controlling Lepidoptera pests with this new mode of action to provide more sustainable and reliable technologies to field management. New data on genomics of this taxon encourage the increment of a customized target genes portfolio. As a case of study, we illustrate how dsRNA and associated methodologies could be applied to control an important Lepidopteran coffee pest.

The prediction of drug-target interactions plays a fundamental role in facilitating drug discovery, where the goal is to find prospective drug candidates. With the increase in the number of drug-protein interactions, machine learning techniques, especially deep learning methods, have become applicable for drug-target interaction discovery because they significantly reduce the required experimental workload. In this paper, we present a spontaneous formulation of the drug-target interaction prediction problem as an instance of multi-instance learning. We address the problem in three stages, first organizing given drug and target sequences into instances via a private-public mechanism, then identifying the predicted scores of all instances in the same bag, and finally combining all the predicted scores as the output prediction. A comprehensive evaluation demonstrates that the proposed method outperforms other state-of-the-art methods on three benchmark datasets.

Inflammatory bowel disease (IBD) is a chronic and relapsing disease caused by a dysregulated immune response to host intestinal microbiota that occurs in genetically predisposed individuals. IBD encompasses two major clinical entities: ulcerative colitis (UC), which is limited to the colonic mucosa, and Crohn disease (CD), which might affect any segment of the gastrointestinal tract. Despite the prevalence of IBD is increasing worldwide, therapy remains suboptimal, largely because the variability of causative mechanisms, raising the need to develop individualized therapeutic approaches targeted to each individual patient. In this context, patients-derived intestinal organoids represent an effective tool for advancing our understanding on IBD’ s pathogenesis. Organoid 3D culture systems offer a unique model for dissecting epithelial mechanisms involved IBDs and test individualized therapy, although the lack of a functional immune system and a microbiota, two driving components of the IBD pathogenesis, represent a major barrier for their exploitation in clinical medicine. In this review we have examined how to improve the translational utility of intestinal organoids in IBD and how co-coltures of 3D or 2D organoids and immune cells and/or intestinal microbiota might help to overcome these limitations.

The advancement of precision medicine critically depends on the robustness and specificity of the carriers used for the targeted delivery of effector molecules in the human body. Numerous nanocarriers have been explored in vivo, to ensure the precise delivery of molecular cargos via tissue-specific targeting, including the endocrine part of the pancreas, thyroid, and adrenal glands. However, even after reaching the target organ, the cargo-carrying vehicle needs to enter the cell and then escape from lysosomal destruction. Most of artificial nanocarriers suffer from intrinsic limitations that either prevent them from completing the specific delivery of the cargo. In this respect, extracellular vesicles (EVs) seem to be the natural tool for payload delivery due to their versatility and low toxicity. However, EV-mediated delivery is not selective and usually short-ranged. By inserting the viral membrane fusion proteins into exosomes, it is possible to increase the efficiency of membrane recognition and also ease the process of membrane fusion. This review describes the molecular details of the viral-assisted interaction between the target cell and extracellular vesicles. We also discuss the question of the usability of viral fusion proteins in developing extracellular vesicle-based nanocarriers with higher efficacy of payload delivery. Finally, this review specifically highlights the role of Gag and RNA binding proteins in RNA sorting into extracellular vesicles.

Multiplex genome editing may induce genotoxicity and chromosomal rearrangements due to double-strand DNA breaks at multiple loci simultaneously induced by programmable nucleases, including CRISPR/Cas9. However, recently developed base-editing systems can directly substitute target sequences without double-strand breaks. Thus, the base-editing system is expected to be a safer method for multiplex genome-editing platforms for livestock. Target-AID is a base editing system composed of PmCDA1, a cytidine deaminase from sea lampreys, fused to Cas9 nickase. It can be used to substitute cytosine for thymine in 3-5 base editing windows, 18 bases upstream of the protospacer-adjacent motif site. In the current study, we demonstrated Target-AID-mediated base editing in porcine cells for the first time. We targeted multiple loci in the porcine genome using the Target-AID system and successfully induced target-specific base substitutions with up to 63.15% efficiency. This system can be used for the further production of various genome-engineered pigs.

In microwave imaging it is often of interest to inspect electrically large spatial regions. In these cases, data must be collected over a great deal of measurement points which entails long measurement time and/or costly, and often unfeasible, measurement configurations. In order to counteract such drawbacks, we have recently introduced a microwave imaging algorithm which looks for the scattering targets in terms of equivalent surface currents supported over a given reference plane. While this method is suited to detect shallowly buried targets, it allows to independently process each frequency data, hence the source and the receivers do not need to be synchronized. Moreover, spatial data can be reduced at large extent, without incurring in aliasing artefacts, by properly combining single-frequency reconstructions. In this paper, we validate such an approach by experimental measurements. In particular, the experimental test site consists of a sand box in open air where metallic plate targets are shallowly buried (few cm) under the air/soil interface. The investigated region is illuminated by a fixed transmitting horn antenna whereas the scattered field is collected over a planar measurement aperture at a fixed height from the air-sand interface. The transmitter and the receiver share only the working frequency information. Experimental results confirm the feasibility of the method.

Abstract: Molybdenum (Mo) thin films were sputtered from two kinds of Mo targets with different microstructures under the same sputtering process, and the effect of microstructure of Mo target on morphology, deposition rate and resistance of sputtered film were studied and discussed. The results show that morphological differences between Mo thin films sputtered by Mo targets with different microstructures are very small. The more uniform and finer the grain structures of Mo target, the better the uniformity on thickness and resistance of Mo sputtered film. Moreover, during sputtering process, when Mo target’s grain size is finer and the surface area of grain boundary is higher, the thickness reduction of the target is more homogeneous and the sputtering film has faster deposition velocity. The difference in microstructure of the Mo target has not obvious influence on the grain orientation of sputtering film.

We are in a new chapter of crop and livestock improvement with the emergence of genome editing. This latest generation of molecular tools can be used to make targeted changes in a genome including insertions, deletions, and mutations. With new advances comes new risks for unintended changes and impacts, thus the need for appropriate risk assessment for product development and to inform regulatory measures. Though CRISPR/Cas has arisen as the predominant technology, there are multiple types of genome editing tools each with pros and cons depending on the organism and desired outcome. Furthermore, each editing tool differs in specificity as they may edit non-intended sites, referred to as off-target edits. The consensus of the agricultural editing community is to avoid off-target editing through design and detection, instead of determining whether off-target editing in each case is detrimental. The design of a targeting component, the tool chosen, and the identification of the edit(s) made are the critical factors in avoiding off-target edits and confirming intended edits in final products that are released commercially. The limited amount of head-to-head comparisons of genome editing tools in diverse crops and livestock make it difficult to develop broad conclusions and best practices, which is further compounded by the diversity of techniques, targets, and processes. Developers and breeders should consult the literature and test as needed to determine which editing technology will be the most effective for their purposes, especially as more tools with altered efficiency and specificity become available. Yet, the lack of off-target edits in studies that employed careful design of targeting components followed by wide testing for on- and off-target edits bodes well for the use of genome editing with proper precautions of target selection and screening.

All countries are facing decisions about which groups to prioritise for COVID-19 vaccination after the first vaccine product has been licensed, at which time supply shortages are inevitable. Here we define the key target populations and their size in China for a phased introduction of COVID-19 vaccination with evolving goals, accounting for the risk of illness and transmission. Essential workers (47.2 million) like healthcare workers could be prioritized for vaccination to maintain essential services. Subsequently, older adults, individuals with underlying health conditions and pregnant women (616.0 million) could be targeted to reduce severe COVID-19 outcomes. Then it could be further extended to target adults without underlying health conditions and children (738.7 million) to reduce symptomatic infections and/or to stop virus transmission. The proposed framework could assist Chinese policy-makers in the design of a vaccination program, and could be generalized to inform other national and regional COVID-19 vaccination strategies.