The increasing emergence of multidrug resistant (MDR) pathogens, due to antibiotics misuse, translates in obstinate infections, with high morbidity and high-cost hospitalizations. To oppose these MDR superbugs, new antimicrobial options are necessary. Although both quaternary ammonium (QASs) and phosphonium salts (QPSs) possess antimicrobial effects, QPSs have been studied at lesser extent. Recently, we have successfully reported on the bacteriostatic and cytotoxic effects of a triphenyl phosphonium salt against MDR isolates of Enterococcus and Staphylococcus genus. Here, aiming at finding new antibacterial devices possibly bactericidal towards a broader spectrum of clinically relevant bacteria, responsible for severe human infections, we synthesized a water-soluble, sterically hindered quaternary phosphonium salt (BPPB). It encompasses two triphenyl phosphonium groups linked by a C12 alkyl chain, thus embodying the characteristics of molecules known as bola-amphiphiles. BPPB was characterized by ATR-FTIR, NMR and UV spectroscopy, FIA-MS (ESI), elemental analysis and potentiometric titrations. Optical and DLS analyses evidenced BPPB tendency to self-forming spherical vesicles in solution (45 nm by DLS), having a positive zeta potential (+18 mV). The antibacterial effects of BPPB were for the first time assessed against fifty clinical isolates of both Gram-positive and Gram-negative species. Excellent antibacterial effects were observed on all strains tested, involving all the most worrying species included in ESKAPE bacteria. The lowest MICs were 0.250 µg/mL, while the highest ones (32 µg/mL) were observed on MDR Gram-negative metallo-β-lactamase-producing bacteria and/or species resistant also to colistin, carbapenems, cefiderocol, so that intractable with current available antibiotics. Moreover, when administered to HepG2 human hepatic and Cos-7 monkey kidney cell lines, BPPB showed selectivity indices > 10 for all Gram-positive isolated and for clinically relevant Gram-negative superbugs such as those of E. coli species, thus being very promising to be clinically developed.

(1) Background: Depressional wetlands are highly vulnerable to changes in temperature and rainfall, affecting littoral vegetation, thus HydroGeoMorphic (HGM) wetland types. This study aimed to assess the utility of Sentinel-2A vegetation indices in enhancing delineation and sub-classify depressional HGM types. (2) Methods: We sampled 84 pairs of four vegetation indices from 10x10m plots along 14 belt transects in eight depressional wetlands in Mpumalanga, South Africa. We evaluated vegetation index differences between and within wetlands, focusing on lit-toral gradients. (3) Results: Significant differences (Bonferroni p

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease caused by mutations to the dystrophin gene - resulting in deficiency of dystrophin protein, loss of myofiber integrity in skeletal and cardiac muscle, and eventual cell death and replacement with fibrotic tissue. Pathologic cardiac manifestations occur in nearly every DMD patient, with development of cardiomyopathy - the leading cause of death - inevitable by adulthood. As early cardiac abnormalities are difficult to detect, timely diagnosis and appropriate treatment modalities remain a challenge. There is no cure for DMD – treatment is aimed at delaying disorder progression and alleviating symptoms. A comprehensive understanding of the pathophysiological mechanisms is crucial to development of targeted treatments. While established hypotheses of underlying mechanisms include sarcolemmal weakening, upregulation of pro-inflammatory cytokines, and perturbed ion homeostasis, mitochondrial stress has recently come into focus as a potential key contributor. Several experimental compounds targeting the skeletal muscle pathology of DMD are in development, but effects of such agents on cardiac function remain unclear. Synergistic integration of small molecule- and gene-target-based drugs with metabolic, immune, or ion balance-enhancing compounds into a combinatorial therapy offers potential for treating dystrophin deficiency-induced cardiomyopathy, making it crucial to understand the underlying mechanisms driving the disorder.

In the dynamic landscape of drug discovery, Computer-rAided Drug Design (CADD) emerges as a transformative force, bridging the realms of biology and technology. This paper overviews CADD's historical evolution, categorization into structure-based and ligand-based approaches, and its crucial role in rationalizing and expediting drug discovery. As CADD advances, incorporating diverse biological data and ensuring data privacy become paramount. Challenges persist, demanding the optimization of algorithms and robust ethical frameworks. Integrating Machine Learning and Artificial Intelligence amplifies CADD's predictive capabilities, yet ethical considerations and scalability challenges linger. Collaborative efforts and global initiatives, exemplified by platforms like Open Source Malaria, underscore the democratization of drug discovery. The convergence of CADD with personalized medicine offers tailored therapeutic solutions, though ethical dilemmas and accessibility concerns must be navigated. Emerging technologies like quantum computing, immersive technologies, and green chemistry promise to redefine the future of CADD. The trajectory of CADD, marked by rapid advancements, anticipates challenges in ensuring accuracy, addressing biases in AI, and incorporating sustainability metrics. The paper concludes by highlighting the need for proactive measures in navigating the ethical, technological, and educational frontiers of CADD to shape a healthier, brighter future in drug discovery.

Thanks to the continued development of experimental structural biology and the half-a-century old Protein Data Bank, 2021 saw a big step forward in the development of protein structure prediction with deep learning algorithms. Recently, DeepMinds AlphaFold has determined the structures of ∼ 200 million proteins from 1 million species. The speed of this progress raise the question of what becomes possible for computational drug discovery and design when we have a systems-wide account of the structures and motions of most proteins. Therefore, this article puts forward the concept of a general intermolecular binding affinity calculator (GIBAC): Kd = f(molA, molB, envPara), towards the acceleration of traditional computer-aided drug design (CADD) and artificial intelligence-integrated drug discovery (AIDD), for both small molecules and biologics such as therapeutic proteins.

The delineation of the clinical target volumes (CTVs) for radiation therapy is time-consuming, requires intensive training and shows high inter-observer variability. Supervised deep learning methods depend heavily on consistent training data, thus state-of-the-art research focuses on making CTV labels more homogeneous and strictly bounding them to current standards. International consensus expert guidelines standardize CTV delineation by conditioning the extension of the clinical target volume on surrounding anatomical structures. Training strategies that directly following the construction rules given in the expert guidelines or the possibility to quantify the conformance of manually drawn contours with the guidelines are still missing. 71 anatomical structures that are relevant for CTV delineation in head and neck cancer patients according to the expert guidelines were segmented on 104 CT scans to assess the possibility to automate their segmentation by state-of-the-art deep learning methods. nnU-Net models were trained to automatically segment those 71 structures on planning CT scans. We report the DICE, HD and sDICE for 71 + 5 anatomical structures for most of which no previous segmentation accuracies have been reported. For those structures, for that prediction values have been reported, our segmentation accuracy matched or exceeded the reported values. The predictions from our models were always better than those predicted by the TotalSegmentator. The sDICE with 2mm margin was larger than 80% for almost all structures. Individual structures with decreased segmentation accuracy are analyzed and discussed with respect to their impact on the CTV delineation following the expert guidelines. No deviation is expected to affect the rule-based automation of the CTV delineation.

The network pharmacology (NP) approach is a valuable novel methodology for understanding the complex pharmacological mechanisms of medicinal herbs. In addition, various in silico analysis techniques combined with the NP can improve the understanding of various issues in natural product research. This study assessed the therapeutic effects of Arum ternata (AT), Poria cocos (PC), and Zingiber officinale (ZO) on hyperlipidemia after network pharmacologic analysis. A protein–protein interaction (PPI) network of forty-one key targets was analyzed to discover core functional clusters of the herbal compounds. The KEGG pathway and gene ontology (GO) term enrichment analysis identified significant categories of hypolipidemic mechanisms. The STITCH database indicated a high connection with several statin drugs deduced by the similarity in targets. AT, PC, and ZO regulated the genes related to the energy metabolism and lipogenesis in HepG2 cells loaded with free fatty acids (FFAs). Furthermore, a combinational effect of the mixture of three herbs was found. The herbal combination exerted superior efficacy compared to a single herb, particularly in regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1 (CPT-1). In conclusion, the network pharmacologic approach was used to assess potential targets of the herbal combination for treatment. Experimental data from FFAs-induced HepG2 cells suggested that the combination of AT, PC, and ZO might attenuate hyperlipidemia and its associated hepatic steatosis.

This investigation introduces an efficient method for assessing the reliability of semi-rigid steel frame connections in existing buildings, explicitly targeting the Top Angle and Seat Pad (TA-SP) semi-rigid connection commonly used in Australian cities' high-rise buildings. The moment capacity of these connections was examined through parameter power model testing, meticulously considering the bending, shear, and prying forces actions to determine the weakest elements in the connection system. A plastic hinge model was applied to ensure computational efficiency and accuracy in assessing the connections' ultimate strength. Comparatively, the finite element (F.E) method M−θ curves were introduced to scrutinise the nonlinear behaviour of the connection, providing validation for the predicted analytical approach. Further emphasis was placed on identifying the reliability of the weakest elements in the connection system, employing the First-Order and Second-Order Reliability Methods models to estimate their reliability index. The correlation between the model's failure probability and a percentile error was also explored, utilising Monte Carlo simulation reference for refined validation. Novel formulas and methodologies were introduced to compute the locked-chain-series system reliability, which accounts for the inherent material and geometric variability. The findings highlight the critical significance of the weakest element in determining the overall reliability of the existing TA-SP connection.

The effectiveness of a recently proposed methodology in the identification of damage in planar, multi-storey, Reinforced Concrete (RC) moment-frames, which develop a plastic-yield mechanism on their beams, is showcased here via the examining of a group of such existing multi-storey frames with three or more unequal spans. According to the methodology, the diagram of the instantaneous Eigen-Frequencies of the frame in the nonlinear regime is drawn as a function of the inelastic seismic roof displacement by performing a sequence of pushover and instantaneous modal analyses with gradually increasing target displacement. Using this key-diagram, the locations of severe seismic damage in an existing moment-frame can be evaluated if the instantaneous fundamental eigen-frequency of the damaged frame, at an analysis step within the nonlinear area, is known in advance by “the monitoring and the identification of frequencies” using a local network of uniaxial accelerometers. This is a hybrid technique because both procedures, the instrumental Monitoring of the structure and the Pushover analysis on the frame (M and P technique), are combined. Moreover, the damage image of the planar multi-storey moment-frame is illustrated, and the lateral stiffness matrix of the damaged frame is calculated with high accuracy.

Research on healthy ageing shows that lifespan reductions are often caused by mitochondrial dysfunction. Thus, it is very interesting that the deletion of mitochondrial matrix peptidase LonP1 was observed to abolish embryogenesis, while deletion of the mitochondrial matrix peptidase ClpP prolonged survival. To unveil the targets of each enzyme, we documented the global proteome of LonP1^+/- mouse embryonal fibroblasts (MEF), for comparison with ClpP^-/- depletion. Proteomic profiles of LonP1^+/- MEF generated by label-free mass spectrometry were further processed with the STRING webserver Heidelberg for protein interactions. ClpP was previously reported to degrade Eral1 as a chaperone involved in mitoribosome assembly, so ClpP deficiency triggers accumulation of mitoribosomal subunits and inefficient translation. LonP1^+/- MEF also showed Eral1 accumulation, but no systematic effect on mitoribosomal subunits. In contrast to ClpP^-/- profiles, several components of the respiratory complex I membrane arm were accumulated, whereas the upregulation of numerous innate immune defense components was similar. Overall, LonP1 as opposed to ClpP appears to have no effect on translational machinery, instead it shows enhanced respiratory dysfunction; this agrees with reports on the human CODAS syndrome caused by LonP1 mutations.

The Xpert® Xpress SARS-CoV-2 and Xpert® Xpress SARS-CoV-2/Flu/RSV tests were rapidly developed and widely used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In response to emerging genetic variability, a new SARS-CoV-2 target (RNA-dependent RNA-polymerase) has been added to both tests: Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus test. A rapid evaluation of both tests was performed in South Africa, using residual respiratory specimens. Residual respiratory specimens (n=125) were used to evaluate the Xpert® Xpress CoV-2 plus test and included 50 genotyped specimens. The Xpert® Xpress CoV-2/Flu/RSV plus test was assessed using 45 genotyped SARS-CoV-2 specimens, ten influenza A, ten Influenza B and twenty respiratory syncytial virus specimens. Results were com-pared to in-country standard of care tests. Genotyped specimens tested the performance of the test under pressure from circulating SARS-CoV-2 variants of concern. Reference material was included to assess the test limits and linearity. The Xpert® Xpress CoV-2 plus test performance compared to reference results across residual respiratory specimens was good (positive per-centage agreement (PPA)=95.2%, negative percentage agreement (NPA)=95.0%) The Xpert® Xpress CoV-2/Flu/RSV plus test showed good performance across all residual respiratory specimens (PPA=100%, NPA=98.3%). All genotyped variants of concern were detected by both tests. The Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus tests can be used to diagnose SARS-CoV-2, and to diagnose and differentiate SARS-CoV-2, influenza A, influenza B and respiratory syncytial virus respectively. The NPA was lower than the recommended 99%, but was influenced by the low number of negative specimens tested. The variants of concern assessed did not affect test performance. It is recommended that sites perform their own assessments compared to in-country standard of care tests.

For the in-house validation of a droplet digital PCR method, a factorial experimental design was implemented. This design serves different purposes. On the one hand, it is an efficient design in relation to the workload involved in achieving a desirable level of reliability of variance estimates. On the other hand, it allows a partitioning of total variance into different components, thus providing information regarding the dominant sources of random variation. The statistical modelling reflects the actual measurement mechanism, establishing relationships between nominal target DNA copies per well, the range of variation of copy numbers per droplet, probability of detection values, and estimated numbers of copies.

The knowledge of what separates us genetically from our less-evolved relatives is crucial for gaining new biomedical insights about the human-chimpanzee relatedness for the use of appropriate stand-in towards the development of new treatments and diagnostic aids for various ailments. Although the genomes of humans and chimpanzees share 99% similarity, significant differences exist between the two species in their non-coding intronic regions. However, no work has been carried out in the aspects of target prediction concerning the ‘predicted homology’ in their microRNA sequences. Non-coding miRNAs which are post-transcriptional regulators of development, differentiation, growth, and metabolism, harboring the intronic regions may be crucial for expanding the horizons of our understanding. In this study, we proposed to perform the target prediction for the human-chimp miRNA homologs in the PHEX gene of the human X chromosome using various computational tools and databases. We identified a total of 1296 human miRNAs, 46, 957 gene targets, and 30, 563 targets of human and homologous chimp miRNAs respectively. Furthermore, we analysed gene interacting networks to identify the top interacting targets in both the species. Finally, we interpreted the biological importance of top-interacting miRNAs and their targets. The results demonstrated varying levels of multiplicity and cooperativity between the predicted miRNAs and target genes in the two genera. Such miRNAs may be responsible for the dysregulation of gene expression in several signaling pathways.

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.

The world is currently experiencing the fourth industrial revolution driven by the newest wave of digitisation in the manufacturing sector. The term Industry 4.0 (I4.0) represents at the same time: a paradigm shift in industrial production, a generic designation for sets of strategic initiatives to boost national industries, a technical term to relate to new emerging business assets, processes and services, and a brand to mark a very particular historical and social period. I4.0 is also referred to as Industrie 4.0 the New Industrial France, the Industrial Internet, the Fourth Industrial Revolution and the digital economy. These terms are used interchangeably in this text. The aim of this article is to discuss major developments in this space in relation to the integration of new developments of IoT and cyber physical systems in the digital economy, to better understand cyber risks and economic value and risk impact. The objective of the paper is to map the current evolution and its associated cyber risks for the digital economy sector and to discuss the future developments in the Industrial Internet of Things and Industry 4.0.

In recent years, the unmanned aerial vehicle (UAV) synthetic aperture radar (SAR) has become a highly sought-after topic for its wide applications in the field of target recognition, detection, and tracking. However, SAR automatic target recognition (ATR) models based on deep neural networks (DNN) are suffering from adversarial examples. Generally, non-cooperators rarely disclose any information about SAR-ATR models, making adversarial attacks challenging. In this situation, we propose Transferable Adversarial Network (TAN) to attack these models with highly transferable adversarial examples. The proposed method improves the transferability via a two-player game, in which we simultaneously train two encoder-decoder models: a generator that crafts malicious samples through a one-step forward mapping from original data, and an attenuator that weakens the effectiveness of malicious samples by capturing the most harmful deformations. In particular, compared to traditional iterative methods, our approach is able to one-step map original samples to adversarial examples, thus enabling real-time attacks. Experimental results indicate that the proposed approach achieves state-of-the-art transferability with acceptable adversarial perturbations and minimum time costs compared to existing attack methods, i.e., it excellently realizes real-time transferable adversarial attacks.

The Internet-of-Things (IoT) enables enterprises to obtain profits from data but triggers data protection questions and new types of cyber risk. Cyber risk regulations for the IoT however do not exist. The IoT risk is not included in the cyber security assessment standards, hence, often not visible to cyber security experts. This is concerning, because companies integrating IoT devices and services need to perform a self-assessment of its IoT cyber security posture. The outcome of such self-assessment needs to define a current and target state, prior to creating a transformation roadmap outlining tasks to achieve the stated target state. In this article, a comparative empirical analysis is performed of multiple cyber risk assessment approaches, to define a high-level potential target state for company integrating IoT devices and/or services. Defining a high-level potential target state represent is followed by a high-level transformation roadmap, describing how company can achieve their target state, based on their current state. The transformation roadmap is used to adapt IoT risk impact assessment with a Goal-Oriented Approach and the Internet of Things Micro Mart model.

Recent studies have proven that synthetic aperture radar (SAR) automatic target recognition (ATR) models based on deep neural networks (DNN) are vulnerable to adversarial examples. However, existing attacks are easily failed in the case where adversarial perturbations cannot be fully fed to victim models. We call this situation perturbation offset. Moreover, since background clutter takes up most of the areas in SAR images and has low relevance to recognition results, fooling models with global perturbations is quite inefficient. This paper proposes a semi-whitebox attack network, called Universal Local Adversarial Network (ULAN), to generate universal adversarial perturbations (UAP) for the target regions of SAR images. In the proposed network, we calculate the model’s attention heatmaps through layer-wise relevance propagation (LRP), which is used to locate the target regions of SAR images that have high relevance to recognition results. In particular, we utilize a generator based on the U-Net to learn the mapping from noise to UAPs and craft adversarial examples by adding the generated local perturbations to target regions. Experiments indicate that the proposed method fundamentally prevents perturbation offset and achieves comparable attack performance to conventional global UAPs by perturbing only a quarter or less of SAR image areas.

Target 12.3 of the United Nations Sustainable Development Goals (SDGs) calls for halving per capita global food waste at the retail and consumer levels, by 2030. The Food Waste Index is suggested as a methodology for grasping the situation. This paper focuses on the consumer level (household food waste). We argue that in order for generating useful information for devising and implementing effective measures for reducing food waste, it should be measured at Level 3 of the Food Waste Index, based on sorting analysis of generated waste, making a distinction between avoidable and non-avoidable food waste. Furthermore, a breakdown by sub-categories that reflect the flow of food in the household could help identify target behaviours. We have developed a categorisation scheme that is internationally agreeable and adoptable, and 1) generates useful information for policy-making and for tackling with reduction of food waste, 2) makes clear the concept of avoidable food waste, and 3) is practical and does not overcomplicate the work of grasping the situation of food wastage. Results of workshops regarding this scheme suggest that the scheme satisfies the criteria. This scheme has been applied to a few sorting analyses of household food waste in Japan, and their results are compared.

In this paper, based on the symmetrical reliability theory, a research method for the safety factor of overall overturning stability of continuous beam bridge under carbon fiber reinforced polymers (CFRP) during cantilever and horizontal rotation construction is proposed. Under the premise that the given target reliability index is known, the method solves the overall overturning stability safety factor of continuous beam bridge under carbon fiber reinforced polymers during cantilever and horizontal rotation construction by using the symmetrical reliability analysis theory and considering the randomness of structural parameters. This method is used to calculate the safety factor and the design reinforcement aera of CRFP of overturning stability and the design reinforcement aera of CRFP of a continuous beam bridge, and the parameters are analyzed. The calculation results show that the randomness of parameters will have a great impact on the overall safety factor and the CRFP aera of overturning stability of cantilever and horizontal rotation construction of continuous beam bridge, and ignoring the influence of randomness of parameters will lead to overestimation of the overall safety factor and underestimation of the CRFP aera of overturning stability of cantilever and horizontal rotation construction of continuous beam bridge.

The safe and reliable operation of autonomous vehicles in complex and dynamic environments is heavily dependent upon exteroceptive and proprioceptive sensors. A LiDAR system generates accurate 3D point clouds, which are crucial for the detection, classification, and tracking of multiple targets. LiDAR data, however, presents significant challenges due to its density, noise, and varying sampling rates. In this study, various clustering and MTT techniques for LiDAR point clouds will be identified and classified within the context of autonomous driving to assess the state-of-the-art methods’ key challenges and their performances. We have categorized clustering and MTT methods used in AV applications, identified research gaps and challenges and analyzed existing algorithms and their challenges in detail. Researchers and practitioners in the field of autonomous driving will find this review to be a valuable resource.

In the event of an abrupt sunlight reduction scenario there is a time window that occurs between when food stores would likely run out for many countries (~6 months or less) and ~1 year when resilient foods are scaled up. A promising temporary resilient food is leaf protein concentrate (LPC). Although it is possible to extract LPC from tree biomass (e.g. leaves and needles), neither the yields nor the toxicity of the protein concentrates for humans from the most common tree species has been widely investigated. To help fill this knowledge gap, this study uses high-resolution mass spectrometry and an open source toolchain for non-targeted screening of toxins on five common North American coniferous species: Western Cedar, Douglas Fir, Ponderosa Pine, Western Hemlock, and Lodgepole Pine. The yields for LPC extraction from the conifers ranged from 1% to 7.5%. The toxicity screenings confirm that these trees may contain toxins that can be consumed in small amounts and additional studies including measuring the quantity of each toxin are needed. The results indicate that LPC is a promising candidate to be used as resilient food, but future work is needed before LPCs from conifers can be used as a wide-scale human food.

The current SARS-CoV-2 pandemic is still threatening humankind. Despite first successes in vaccine development and approval, no antiviral treatment is available for COVID-19 patients. The success is further tarnished by the emergence and spreading of mutation variants of SARS-CoV-2, for which some vaccines are not effective anymore. This highlights the urgent need for antiviral therapies even more. This article describes how the Genome-Scale Metabolic Model (GEM) of the host-virus interaction of human alveolar macrophages and SARS-CoV-2 was refined by incorporating the latest information about the virus’s structural proteins and the mutant variants B.1.1.7 and B.1.351. We confirmed the initially identified guanylate kinase as a potential antiviral target with this refined model and identified further potential targets from the purine and pyrimidine metabolism. The model was further extended by incorporating the virus’ lipid requirements. This opened new perspectives for potential antiviral targets in the altered lipid metabolism. Especially the phosphatidylcholine biosynthesis seems to play a pivotal role in viral replication. The guanylate kinase is even a robust target in all investigated mutation variants currently spreading worldwide. These new insights can guide laboratory experiments for the validation of identified potential antiviral targets. Only the combination of vaccines and antiviral therapies will effectively defeat this ongoing pandemic.

The Internet-of-Things (IoT) triggers new types of cyber risks. Therefore, the integration of new IoT devices and services requires a self-assessment of IoT cyber security posture. By security posture this article refers to the cybersecurity strength of an organisation to predict, prevent and respond to cyberthreats. At present, there is a gap in the state-of-the-art, because there are no self-assessment methods for quantifying IoT cyber risk posture. To address this gap, an empirical analysis is performed of 12 cyber risk assessment approaches. The results and the main findings from the analysis is presented as the current and a target risk state for IoT systems, followed by conclusions and recommendations on a transformation roadmap, describing how IoT systems can achieve the target state with a new goal-oriented dependency model. By target state, we refer to the cyber security target that matches the generic security requirements of an organisation. The research paper studies and adapts four alternatives for IoT risk assessment and identifies the goal-oriented dependency modelling as a dominant approach among the risk assessment models studied. The new goal-oriented dependency model in this article enables the assessment of uncontrollable risk states in complex IoT systems and can be used for a quantitative self-assessment of IoT cyber risk posture.

Spinal Cord Stimulation (SCS) is an effective and validated treatment to address chronic refractory neuropathic pain in Persistent Spinal Pain Syndrome-Type 2 (PSPS-T2) patients. Surgical SCS lead placement is traditionally performed under general anesthesia due to its invasiveness. In parallel, recent works have suggested that Awake Anesthesia (AA), consisting in Target Controlled Intra-Veinous Anesthesia (TCIVA), could be an interesting tool to optimize lead anatomical placement using patient intra-operative feedback. We hypothesized that combining AA with Minimal Invasive Surgery (MIS) could improve SCS outcomes. The goal of this study was to evaluate SCS lead performance (defined by the area of pain adequately covered by paraesthesia generated via SCS), using an intraoperative objective quantitative mapping tool, and secondarily to assess pain relief, functional improvement and change in quality of life with a composite score. We analyzed data from a prospective multicenter study (ESTIMET) to compare the outcomes of 115 patients implanted with MIS under AA (MISAA group) or General Anesthesia (MISGA group), or by Laminectomy under General Anesthesia (LGA group). All in all, MISAA appears to show significantly better performance in terms of patient pain coverage, as well as improved secondary outcomes. One step further, our results suggest that MISAA combined with intra-operative hypnosis could potentialize patient intraoperative cooperation and could be proposed as a personalized package offered to PSPS-T2 patients eligible for SCS implantation in highly dedicated neuromodulation centers.

Leishmaniases are zoonotic vector-borne diseases caused by a wide variety of Leishmania species with complex transmission cycles involving different reservoirs, potential new hosts and vectors. Similarly, to other eukaryotes, Leishmania release extracellular vesicles (LEVs) to play important initial interactions that are crucial to modulate the subsequent systemic immune response on the establishment of infection in humans and others hosts like dogs. Recent studies in endemic areas of Brazil concluded that canine infections were predominantly due to L. amazonensis and not restricted to L. infantum (syn. Leishmania chagasi). Under these premises, the diagnosis of leishmaniasis needs to be improved with the identification of current etiological agent and the histopathologic features, highlighting the differential diagnosis and the molecular components of LEVs. In this way, the dual aim of that study is to register collected observations of natural canine infections, enhancing the relevance of differential diagnosis in companion animals and inserting in vitro results in the field of LEVs that still research gaps to be filled to understand the mechanisms and biological aspects involving the parasite-host interactions. Therefore, improve these studies of Parasitology research is important for diagnostic, prognostic, treatment advances and continuing need for global prevention, control, elimination/eradication of these parasitic infections.