In 2010, Parties to the Convention on Biological Diversity (CBD) adopted the Strategic Plan for Biodiversity 2011–2020 to address the loss and degradation of nature. Subsequently, most biodiversity indicators continued to decline. Nevertheless, conservation actions can make a positive difference for biodiversity. The emerging Post-2020 Global Biodiversity Framework has potential to catalyze efforts to ‘bend the curve’ of biodiversity loss. Thus, the inclusion of a goal on species, articulated as Goal B in the Zero Draft of the Post-2020 Framework, is essential. However, as currently formulated, this goal is inadequate for preventing extinctions, and reversing population declines; both of which are required to achieve the CBD’s 2030 mission. We contend it is unacceptable that Goal B could be met while most threatened species deteriorated in status and many avoidable species extinctions occurred. We examine the limitations of the current wording and propose an articulation with robust scientific basis. A goal for species that strives to end extinctions and recover populations of all species that have experienced population declines, and especially those at risk of extinction, would help to align actors towards the transformative actions and interventions needed for humans to live in harmony with nature.

In this review, several cost-effective thin-film coating methods which include dip-coating, spin-coating, spray-coating, blade-coating, and roll-coating are presented. Each method has its set of advantages and disadvantages depending on the type of application. Not all of them are appropriate for large-scale production due to their certain limitations. That is why the coating method should be selected based on the type and size of substrate including the resolution of the required thin-films. The sol-gel method offers several benefits, such as simplicity in fabrication, excellent film uniformity, the capacity to cover surfaces of any size and over vast areas, and a low processing temperature. Nevertheless, these coating methods are somewhat economical and well managed in low-budget laboratories. Moreover, the produced thin-films are homogeneous and have low-surface roughness. Furthermore, some other thin-film deposition methods such as physical vapor deposition (PVD) and chemical vapor deposition (CVD) are also discussed. Since CVD is not restricted to line-of-sight deposition, a characteristic shared by sputtering, evaporation, and other PVD processes, many manufacturing methods favor it. However, these techniques require sophisticated equipment and cleanroom facility. We aim to provide the pros and cons of thin-film coating methods and let the readers decide the suitable technique for their specific application.

Photonic sensors are innovative devices that leverage the principles of light-matter interaction to enable precise and efficient detection of various physical parameters. These sensors operate by exploiting the interaction between photons, the fundamental particles of light, and matter. The light propagates through an optical waveguide, and a portion of the electromagnetic field extends beyond the waveguide surface, forming the evanescent field. This evanescent field interacts with the surrounding medium, allowing for highly sensitive detection of changes in the refractive index or properties of nearby substances. The underlying concept involves the modulation of light properties, such as intensity, wavelength, or phase, when it interacts with a target substance or undergoes changes in the surrounding environment. The advancements in photonic sensor technology have paved the way for enhanced sensitivity, selectivity, and miniaturization, making them invaluable tools in diverse industries. The ability to harness light-matter interactions for sensing purposes not only facilitates highly sensitive measurements but also allows for non-intrusive and remote monitoring, contributing to the evolution of smart and connected systems. In this overview, the material platforms and waveguide structures are explored that can make highly sensitive photonic devices applied to gas and biosensing applications.

Gas sensing is crucial for detecting hazardous gases in industrial environments, ensuring safety and preventing accidents. Additionally, it plays a vital role in environmental monitoring and control, helping to mitigate pollution and protect public health. Integrated photonic gas sensors are important due to their high sensitivity, rapid response time, and compact size, enabling precise recognition of gas concentrations in real-time. These sensors leverage photonic technologies, such as waveguides and resonators, to enhance performance over traditional gas sensors. Advancements in materials and fabrication techniques could further improve their efficiency, making them invaluable for environmental monitoring, industrial safety, and healthcare diagnostics. In this review, we delved into photonic gas sensors that operate based on the principles of evanescent field absorption (EFA) and wavelength interrogation methods. These advanced sensing mechanisms allow for highly sensitive and selective gas detection, leveraging the interplay of light with gas molecules to produce precise measurements.

In this study, we construct a new Atangana-Baleanu fractional model for whooping cough disease to predict future dynamics of the disease, as well as to suggest strategies to eliminate the disease in an optimal way. We prove that the proposed model has a unique solution which is positive and bounded. To measure contagiousness of the disease, we determine the reproduction number R0 and use it to examine the local and global stability at equilibrium points that have symmetry. Through sensitivity analysis, we determine parameters of the model that are most sensitive to R0. The ultimate aim of this research is to analyze different disease prevention approaches in order to find the most suitable one. For this, we include the vaccination and quarantine compartments in the proposed model and formulate an optimal control problem to assess the effect of vaccination and quarantine rates on disease control in three distinct scenarios. Firstly, we study the impact of vaccination strategy and conclude findings with presentation of graphical results. Secondly, we examine the impact of quarantine strategy on whooping cough infection with possible elimination from the society. Lastly, we implement vaccination and quarantine strategies together to visualize their combine effect on infection control. In addition to the study of an optimal control problem, we examine the effect of fractional order on disease dynamics as well as the impact of constant vaccination and quarantine rates on disease transmission and control. We determine that the optimal control strategy with the three controls is more effective in reducing the spread of whooping cough infection. Implementation of Toufik-Atangana type numercial scheme both for the state and adjoint equations is another contribution of this article.

Cigarette butts (CBs) are the most diffuse waste in the world, often abandoned in the environment without proper disposal. They are dangerous because of the numerous harmful chemicals poten-tially released in the environment. There are, in literature, several technological options for CB recycling, but some critical concerns could affect their effectiveness due to the quality and quantity of CB litter collected in the proper way. The present paper focuses on policy framework social behavior, waste collection and transport and technological processes. The Extended Producer Responsibility scheme for CBs is proposed at European level as an action to tackle CB litter and encourage sustainable product development. The CB waste collection and transport is a key step for bringing CB to the recycling process. The main concern is the small quantity of CBs collected: 0.06 % of the municipal waste and 0.18 % of the unsorted waste in the administrative area of Pe-rugia. Another crucial issue is the need for behavioral interventions to increase education and awareness of smoker citizens, addressing the discrepancy between smokers’ behaviors and beliefs.

In this work, a numerical study on the loop-terminated Mach-Zehnder interferometer (LT-MZI) structure for CO2 gas sensing application is carried out via the finite element method. The sensing arm is covered with a polyhexamethylene biguanide (PHMB) polymer which is highly receptive to CO2 gas. The refractive index of the host material decreases due to the absorption of the CO2 gas resulting in a shift in the interference pattern of the LT-MZI structure. As a result, a redshift in the wavelength is observed in the transmission spectrum of the device. The sensitivity of the device is estimated at 7.63 pm/ppm, 34.46 pm/ppm and 74.78 pm/ppm for the sensing arm length of 5 µm, 10 µm, and 15 µm, respectively. The sensitivity can be further enhanced, however at the cost of the bigger footprint of the device. Utilizing the innovative sensor design, a comprehensive range of CO2 gas concentrations spanning from 0 to 524 ppm is successfully detected. This compact and highly sensitive device serves as a vital tool for monitoring indoor CO2 levels, fostering a healthier breathing environment for all occupants.

This report is on online banking and information systems in online banking. It throws some light on the introduction and historical background of online banking. Next, in this term report online banking information is explained in detailed. We collected a few articles, related to internet banking, on which other researchers have worked. Then further we have brief them into a table where we have mentioned their problems and limitations. Next, we discussed them in detail, giving an overview of each article. Lastly, recommendations for the online banking sectors are also mentioned.

Keywords: Requirements prioritization, Next release plan, Software product planning, Decision support, MoSCoW, AHP, K-Menas, GMM, BIRCH, PAM, Hierarchical, Clustering, Clusters Evaluation

Standards are not only crucial for obtaining a certification for practical use, but also an essential guidance for inferring how and what to simulate as well test experimentally. This paper examines the potential applicability of existing standards from various domains, including aerospace and automotive, to Wing-Structure- Integrated high-pressure Hydrogen Tanks (SWITHs). It highlights the associated challenges and uncertainties, acknowledging the absence of a single, all-encompassing standard for SWITHs. We embark on an exploration aimed at identifying alternative standards that are best suited for SWITHs. The analysis scrutinizes existing standards that could potentially facilitate SWITH certification, with a particular focus on the inclusivity of externally loaded hydrogen tanks. Assessment criteria are established to filter standards that best meet the needs of SWITHs. Through this process, we identify two key standards that present themselves as the most promising alternatives. Moreover, we delineate the technical constraints involved in selecting the maximum nominal working pressure for high-pressure tanks intended for burst tests. Our findings reveal a current upper limit of 525 bar, imposed by the limitations of existing test facilities. The study underscores that these standards should serve as flexible guiding frameworks rather than rigid protocols, encouraging progressive development in the SWITH field.

We introduce the notion of generalized contraction on dualistic partial metric spaces. A fixed point theorem for mappings satisfying above mentioned contraction is obtained. Some consequences of our result are obtained. We construct an example to demonstrate the effectiveness of our result among the corresponding results in partial metric spaces. Our results provide substantial generalizations and improvements of several well known results existing in the comparable literature. We discuss an application of our fixed point results to show the existence of solution of functional equations.

A highly dirt resistant paint for building facades without chemicals harmful to nature and environment, is developed which resolves the unattractive disfigurement of building walls caused by dirt. The experimentation is scientifically and statistically planned with the aid of computer programming. It consists of a sequence of phases which include the selection of appropriate raw materials, adopting of Basic Language computer programming to generate a target population of paint formulations. The average PVC percentage is computed using theory and found to be 54.98% for the target population of 543143 paint formulations hence verifies the literature results. Experimentation and statistical analysis are performed to compare the classical conventional agitator with latest lab equipment like Nano mill and it is concluded that Nano mill performs better on the average than conventional agitator in preparation of paint formulations. Hence the sample of paint formulations is prepared on Nano mill and tested in laboratory using advanced available technology for the analysis and comparison of paint properties to determine the best paint formulation. The results are analyzed using Analysis Of Variance Technique (ANOVA) and it is concluded that the paint formulation named “O3” has the highest dirt resistance on the average. The final selected formula O3 is compared with three other competitor paints in market under natural environment for a period of almost one year. A regression model is also constructed to study the effect of environmental factors like time, temperature and humidity on dirt resistance of paints. It is found that O3 formulation is the best environment friendly which performs equally well with one competitor paint and has higher dirt resistance than two other competitor paint formulations containing harmful chemicals. The regression model of dirt resistance on variables including time, temperature and humidity shows that these factors are significantly affecting the dirt resistance of a given paint at 5% level of significance. 95.34% variation in the dirt resistance of a given paint is due to and explained by the given factors. The regression model is useful to predict the average dirt resistance of a given paint with a certain level of confidence. The project exemplifies the work of an applied research from conceptualization to successful commercialization for the paint industry.

Currently, old-style personal medicare techniques rely mostly on traditional methods, such as cumbersome tools and complicated processes, which can be time-consuming and inconvenient in some circumstances. Furthermore, such old methods need the use of heavy equipment, blood draws, and traditional bench-top testing procedures. Invasive ways of acquiring test samples can potentially cause patients discomfort and anguish. Wearable sensors, on the other hand, may be attached to numerous body areas to capture diverse biochemical and physiological characteristics as a developing analytical tool. Physical, chemical, and biological data transferred via the skin is used to monitor health in various circumstances. Wearable sensors can assess the aberrant conditions of the physical or chemical components of the human body in real-time, exposing the body state in time, thanks to unintrusive sampling and high accuracy. Most commercially available wearable gadgets are mechanically hard components attached to bands and worn on the wrist, with form factors ultimately constrained by the size and weight of the batteries required for the power supply. Wearable gadgets with “skin-like” qualities are a new type of automation that is only starting to make its way out of research labs and into pre-commercial prototypes. In this paper, we studied the recent advancement in battery-powered wearable sensors established on optical phenomena and skin-like battery-free sensors which brings a breakthrough in wearable sensing automation.

Herein, we offer a numerical study on the devising of a unique 2D-heterostructure Photonic crystal (PC) that can split two orthogonally polarized light waves. The analysis is performed via a two-dimensional finite element method (2D-FEM) by utilizing COMSOL Multiphysics software. The device consists of two discrete designs of PC formation. The first PC formation is optimized so that it permits both TE and TM-polarization of light to transmit through it. Whereas the second PC formation possesses a Photonic Bandgap (PBG) only for TE-polarized light. These two formations are combined at an angle of 45 degrees, resulting in a reflection of self-collimated TE-polarized light at an angle of 90 degrees owing to the PBG present in the second PC formation. While permitting the self-collimated TM-polarized light wave to travel uninterrupted. The proposed device has a small footprint of ~10.5 μm2 offering low transmission loss and high polarization extinction ratio which makes it an ideal candidate to be employed as an on-chip polarization division multiplexing system.

In this paper, we have numerically investigated a metasurface based perfect absorber design established on the impedance matching phenomena. The paper comprises of two parts. In the first part, the device performance of the perfect absorber is studied which is composed of a silicon Nano-cylindrical meta-atoms periodically arranged on the thin gold layer. The device design is unique which works for both x-oriented and y-oriented polarized light, besides independent of the angle of incidence. In the second part of the paper, CO2 gas sensing application is explored by depositing a thin layer of functional host material polyhexamethylene biguanide polymer on the metasurface. The refractive index of the host material decreases due to the absorption of the CO2 gas. As a result, the resonance wavelength of the perfect absorber performs a prominent blueshift. With the help of the proposed sensor design based on metasurface, the CO2 gas concentration range of 0-524 ppm is detected. The maximum sensitivity of ~17.3 pm/ppm is acquired for the gas concentration of 434 ppm. The study presented in this work explores the opportunity of utilizing metasurface perfect absorber for gas sensing applications by employing the functional host materials.

Scoring targets in shooting sports is a crucial and time-consuming task that relies on manually counting bullet holes. This paper introduced an automatic score detection model using object detection techniques. The performance of seven models belonging to two different architectural setups was compared. Models like YOLOv8n, YOLOv8s, YOLOv8m, RetinaNet-50, and RetinaNet-101 are single-shot detectors, while Faster RCNN-50 and Faster RCNN-101 belong to the two-shot detectors category. The dataset was manually captured from the shooting range and expanded by generating more versatile data using Python code. Before the dataset was trained to develop models, it was resized (640x640) and augmented using Roboflow API. The trained models were then assessed on the test dataset, and their performance was compared using matrices like mAP50, mAP50-90, precision, and recall. The results showed that YOLOv8 models can detect multiple objects with good confidence scores. Among all, YOLOv8m performed the best with the highest mAP50 value of 96.7%, followed by the performance of YOLOv8s with the mAP50 value of 96.5%. It is suggested that if the system is to be implemented in a real-time environment, YOLOv8s is a better choice since it took significantly less inference time (2.3ms) than YOLOv8m (5.7ms) and yet generated the competitive mAP50.

Evaluation of the mobility behavior of radionuclides in highly saline and alkaline conditions is a major concern for performance assessment of radioactive waste disposal. The aim of this study is to determine the effect of up to 2.8 mol/kgsolution content of NaNO3, onto the solubility and the sorption of U(VI) in a hardened cement-paste (HCP) prepared from an ordinary Portland cement (CEM I). To avoid the interference of the high salt concentration (and ionic strength) and because of expected low solubility of uranium under such alkaline conditions, the time-resolved laser fluorescence (TRLFS) was selected to measured accurate U(VI) concentration in solution using the standard addition method in 85% H3PO4 to limit dilution and matrix effects and allows determining of resulting [U(VI)] in solution with acceptable precision for distribution factor (Rd) both in sorption and desorption experiments. The operational solubility limit measured at high ionic strength is lowered by a factor 3 compared to the reference cementitious condition, with the Rd values decrease by ca. a factor 4. Sorption of U(VI) appears to be reversible under these conditions.

Diffuse large B cell lymphoma (DLBCL) is curable with chemoimmunotherapy in ~65% of patients. One of the hallmarks of the pathogenesis and resistance to therapy in DLBCL is inhibition of apoptosis, which allows malignant cells to survive and acquire further alterations. Inhibition of apoptosis can be the result of genetic events inhibiting the intrinsic or extrinsic apoptotic pathways, as well as their modulators, such as the inhibitor of apoptosis proteins, P53, and components of the NF-kB pathway. Mechanisms of dysregulation include upregulation of anti-apoptotic proteins and downregulation of pro-apoptotic proteins via point mutations, amplifications, deletions, translocations, and influences of other proteins. Understanding the factors contributing to resistance to apoptosis in DLBCL is crucial in order to be able to develop targeted therapies that could improve outcomes by restoring apoptosis in malignant cells. This review describes the genetic events inhibiting apoptosis in DLBCL, provides a perspective of their interactions in lymphomagenesis, and discuss their implication for the future of DLBCL therapy.

This study analyzes the natural and social factors influencing the emergence and publicization of the invasive status of a fast growing bush, gorse (Ulex europaeus), by comparison between countries on a global scale. We used documents collected on the web in a standardized way. The results show that in all the countries studied, there are several public statuses attributed to gorse. The invasive status is the one that is most shared. The other most frequently encountered status are those of noxious weed, and of economically useful. The invasive status is publicized in nearly all countries, including those where gorse is almost absent. We quantified the publicization of the invasive gorse status of gorse by an indicator with 5 levels, and then performed a multivariate analysis that combines natural and social explanatory variables. The results lead us to propose the concept of invasive niche: the set of natural and social parameters that allow a species to be considered invasive in a given socio-ecosystem.

Herein, a novel cavity design of racetrack integrated circular cavity established on metal-insulator-metal (MIM) waveguide is suggested for refractive index sensing application. Over the past few years, we have witnessed several unique cavity designs to improve the sensing performance of the plasmonic sensors created on the MIM waveguide. The optimized cavity design can provide the best sensing performance. In this work, we have numerically analyzed the device design by utilizing the finite element method (FEM). The small variations in the geometric parameter of the device can bring a significant shift in the sensitivity and FOM of the device. The best sensitivity and FOM of the anticipated device are 1400 nm/RIU and ~12.01, respectively. We believe that the sensor design analyzed in this work can be utilized in the on-chip detection of biochemical analytes.

Algaecides are chemicals that cause serious health problems. Conventional paints contain algaecides to improve the algae resistance on the paint film. Present research has suggested an environmental friendly paint formulation that focuses on developing algae resistance without having algaecides. In this research, Algae growth on newly developed paint is modeled by incorporating dirt resistance of paint and natural phenomena including humidity, temperature and time respectively. The fitted Model revealed explained variation of 59.65% in the average algae growth, of which, Dirt Resistance, Humidity and temperature and some of their interactions play significant role in this variation. Model suggests that the proposed newly developed paint without algaecides is more resilient to algae growth and significantly decreased the average algae growth rate by 0.53% as compared to conventional paints. Keeping the effect of all other factors constant, if dirt resistance of paint (D_c value) increases by one percent, average algae growth decreases by 12.98%; when temperature increases by 1^oC, average algae growth decreases by 22.4%; a positive unit change in the joint linear effect dirt resistance, temperature and humidity caused a decrease in average algae growth by 0.0031%. It was also observed that the individual effect of humidity variable was inversely related with average algae growth. However the combination of humidity and temperature, humidity and dirt resistance, humidity and time, and the quadratic effect of humidity were found to increase the average algae growth rate. The cubic effect of temperature variable by one degree centigrade resulted in decrease of average algae growth by 0.000907%.

We demonstrated a new approach to the production of three-dimensional-coated patterns using liquid route. Metallic perovskite oxides were coated onto three-dimensional (3D) microstructured substrates with different aspect ratios. The success of the method relies on the solution viscosity monitored by adding viscous liquid. The process of oxide thin films consists in three steps: preparing the precursor solution, coating the solution by spin-coating process onto three-dimensional-Si substrates and post-annealing. The chemical solution 3D-coating is conformal.

With increasing power and speed of laser welding, in-process monitoring has become even more crucial to ensure process stability and weld quality. Due to its low cost and installation flexibility, acoustic process monitoring is a promising method and has demonstrated its effectiveness. Since its feasibility has been the focus of existing studies, the temporal resolution of acoustic emissions (AE) has not yet been addressed despite its utmost importance for realizing real-time systems. Aiming to provide a benchmark for further development, this study investigates the relationship between duration and informativeness of AE signals during high power (3.5kW) and high speed (12m/min) laser beam butt welding. Specifically, the informativeness of AE signals is evaluated based on the accuracy of detecting and quantifying joint gaps for various time windows of signals, yielding numerical comparison. The obtained results show that signals can be shortened up to a certain point without sacrificing their informativeness, encouraging to optimize the signal duration. Our results also suggest that large gaps (> 0.3mm) induce unique signal characteristics in AE, which are clearly identifiable from 1 ms signal segments, equivalent to 0.2mm weld seam.

The impact of large atmospheric attenuation events on data quality and availability is a critical aspect for future altimetry missions based on Ka-band altimetry. The SARAL/AltiKa mission and its Ka-band nadir altimeter offer a unique opportunity to assess this impact. Previous publications (Tournadre et al. 2009, 2015) already analyzed the impact of rain on the waveforms at Ka-band and proposed a definition of an elaborate rain flag. This notion tends to give a simpler black and white view of the atmospheric attenuation when the effect on the altimeter measurement is intense. But in practice, there is continuum of measurements that may be partially distorted or corrupted by rain events. The present study proposes a wider point of view , the ACECAL approach providing statistics on rain cells occurrences as well as their amplitude and their size, as guidelines for future Ka-band missions concerning the impact of the atmosphere. At global scale, 1 % of the measurements are affected by an attenuation larger than 23 dB and 10 % of the atmospheric attenuation events have a size larger than 40 km. This study demonstrates that the data quality and availability over some regions of particular interest for oceanography as Gulf Stream, North Pacific and Brazil currents could be affected compared to global statistics. It also opens some perspectives on the benefits that the community could be drawn from the systematic distribution of the rain cells parameters as secondary products of altimetry missions.

We investigate the human sustainability of ICT and management changes using a French linked employer-employee survey on organizational changes and computerization (COI). We approach the human sustainability of changes through the evolutions of work intensity, skill utilization and the subjective relationship to work. We compare in the private sector and the State civil service the impacts of ICT and management changes on the evolution of these three dimensions of work experience. We find that when ICT and management changes are intense, they are positively associated in the public sector with work intensification and new knowledge. In the private sector ICT and management changes increase the use of skills, but at a rate decreasing with their intensity and without favoring the accumulation of new knowledge. However, their impacts on the subjective relationship to work are much stronger, with public sector employees expressing discouragement as well as the feeling of an increased effort-reward imbalance when private sector employees become more committed. We tested that the self-selection of employees, the specific sources and paths of changes and the implementation of performance pay did not explain this divergence. We identify two partial explanations: one is related with employee turnover in the private sector, the other one with the role of trade unions. These results suggest that the human sustainability of ICT and management changes depends on their intensity and on how their implementation takes into account the institutional context of the organization.

This study aimed to explore the feasibility of using airborne acoustic emission in laser beam butt welding for the development of an automated classification system based on neural networks. The focus was on monitoring the formation of joint gaps during the welding process. To simulate various sizes of butt joint gaps, controlled welding experiments were conducted, and the emitted acoustic signals were captured using audible to ultrasonic microphones. To implement an automated monitoring system, a method based on short-time Fourier transformation was developed to extract audio features, and a convolutional neural network architecture with data augmentation was utilized. The results demonstrated that this non-destructive and non-invasive approach was highly effective in detecting joint gap formations, achieving an accuracy of 98%. Furthermore, the system exhibited promising potential for low latency monitoring of the welding process. The classification accuracy for various gap sizes reached up to 90%, providing valuable insights for characterizing and categorizing joint gaps accurately. Additionally, increasing the quantity of training data with quality annotations could potentially improve the classifier model's performance further. This suggests that there is room for future enhancements in the study.

This paper presents a novel approach of welding thick steel plates that offers time and energy savings compared with conventional techniques. The combination of gas metal arc welding (GMAW) and hot-wire technology simplifies the joint configuration and enhances the process tolerance. In this study, a square butt joint was prepared with as-cut edges and a thickness of 15 mm. The relationship between the welding current and the deposition rate of solo GMAW showed limitations and low process tolerance. Increasing the welding current led to a larger deposited volume with unnecessary weld penetration. An independent deposition volume due to hot-wire insertion was used to improve process tolerance. This approach provided an additional volume without increasing the welding current and reduced unnecessary penetration. With optimized parameters, full-penetration single-pass welding was achieved. Compared with the formation of a typical single-v butt joint at a similar welding speed of 30 cm/min, the proposed process reduced the minimum arc time and power consumption by approximately 83% and 62%, respectively. Moreover, a single pass at a travel speed of 60 cm/min was achieved with approximately 91% and 81% less arc time and power consumption, respectively. In summary, the combined process simplifies the joint configuration, enables full-penetration single-pass welding, and reduces time and energy requirements.

In contemporary science and technology, photonic sensors are essential. They may be made to be extremely resistant to some physical parameters while also being extremely sensitive to other physical variables. Most photonic sensors may be incorporated on chips and operate with CMOS technology, making them suitable for use as extremely sensitive, compact, and affordable sensors. Photonic sensors can detect electromagnetic (EM) wave changes and convert them into an electric signal due to the photoelectric effect. Depending on the requirements, scientists have found ways to develop photonic sensors based on several interesting platforms. In this work, we extensively reviewed the most generally utilized photonic sensors for detecting vital environmental parameters and personal healthcare. These sensing systems include optical waveguides, optical fibers, plasmonics, metasurfaces, and photonic crystals. Various aspects of light are used to investigate photonic sensors' transmission or reflection spectra. In general, resonant cavity or grating-based sensor configurations that work on wavelength interrogation methods are preferred, so these sensor types are mostly presented. We believe this paper will provide insight into the novel types of available photonic sensors.

Environmental monitoring is an important topic and serves a vibrant scientific role by revealing long-term trends that can lead to new knowledge and understanding. Globally, there is active development of photonic sensors incorporating multidisciplinary research. The ultimate objective is to develop small, low-cost, sensitive, selective, quick, durable, remote-controllable sensors that are resistant to electromagnetic interference. Different photonic sensor designs and advances in photonic frameworks have shown the possibility to realize these capabilities. In this review paper, the latest developments in the field of optical waveguide and fiber-based sensors which can serve for environmental monitoring are discussed. Several important topics such as toxic gas, water quality, indoor environment, and natural disaster monitoring are reviewed.

In this paper, the effect of preheating on the mechanical properties and micro structure of similar friction stir welded AA6061 aluminum alloys sheets was investigated. Aluminum alloy 6061 sheets with a thickness of 5 mm and threaded cylindrical pins were used. Rotation and traverse speeds were 1200 rpm and 75 mm/min, respectively. The results of tensile tests performed on the welded samples showed that compared to the non-preheated samples, preheating had increased the strength and elongation of the joints by 58% and 46%, respectively. In the present study, during the welding process preheating cause emerged heat with lower slope from stir zone. This phenomenon may result in Increase the deformation resistance of material and consequently decrease of grain size. This grain refinement can improve the mechanical properties of welds. Accordingly, hardness and strength of the material will be increased.

The construction sector is considered as a major consumer of virgin materials and contributor to waste generation. Therefore, it is essential to rethink current waste management practices, for example, by applying circular economy principles to building demolition, such as deconstruction. Deconstruction involves dismantling a building with the aim of maintaining the highest possible value for its materials and maximize their recovery potential. This study aims to guide the construction sector towards deconstruction to support its efforts to transform itself toward a more sustainable industry. It focuses on a regional case study in the province of Québec (Canada) presenting five buildings to be deconstructed. First, the study presents the outcomes of our analysis of the current situation. Second, it identifies the issues and obstacles encountered and proposes avenues to improve the current process based on solutions identified in the literature and the recommendations of the manager, the contractor involved in the deconstruction process, as well as experts in the construction industry. Finally, it proposes an improved deconstruction process. Our research approach is inspired from Lean thinking and follows Action Research methodology.

Membrane remodeling and phospholipid biosynthesis are normally tightly regulated to maintain the shape and function of cells. Indeed, different physiological mechanisms ensure a precise coordination between de novo phospholipid biosynthesis and modulation of membrane morphology. Interestingly, the overproduction of certain membrane proteins hijack these regulation networks, leading to the formation of impressive intracellular membrane structures in both prokaryotic and eukaryotic cells. The proteins triggering an abnormal accumulation of membrane structures inside the cells (or membrane proliferation) share two major common features: 1) they promote the formation of highly curved membrane domains and 2) they lead to an enrichment in anionic, cone-shaped phospholipids (cardiolipin or phosphatidic acid) in the newly formed membranes. Taking into account the available examples of membrane proliferation upon protein overproduction, together with the latest biochemical, biophysical and structural data, we explore the relationship between protein synthesis and membrane biogenesis. We propose a mechanism for the formation of these non-physiological intracellular membranes that shares similarities with natural inner membrane structures found in α-proteobacteria, mitochondria and some viruses-infected cells, pointing towards a conserved feature through evolution. We hope that the information discussed in this review will give a better grasp of the biophysical mechanisms behind physiological and induced intracellular membrane proliferation, and inspire new applications, either for academia (high-yield membrane protein production and nanovesicle production) or industry (biofuel production and vaccine preparation).

QTc interval measurement is a widely used screening tool to assess the risk of cardiac diseases, arrhythmias, and is a useful biomarker for pharmacovigilance. However, interpretation of QTc is difficult in neonates due to hemodynamic maturational changes and uncertainties on reference values. To describe trends in QTc values throughout infancy (1 year of life), and to explore the impact of (non)-maturational changes and medicines exposure, a structured systematic review (PROSPERO CRD42022302296) was performed. In term neonates, a decrease was observed over the first week of life, whereafter values increased until two months of age, followed by a progressive decrease until six months. A similar pattern, with longer QTc values was observed in preterms. QTc is influenced by cord clamping, hemodynamic changes, therapeutic hypothermia, illnesses and sleep, not by sex. Cisapride, domperidone and doxapram result in QTc prolongation in neo-nates. Further research in this age category is needed to improve primary screening practices, earlier detection of risk factors and precision pharmacovigilance.

Domestic cats (Felis catus) are widespread worldwide as the most popular pets. This medium-sized carnivore have well-known negative effects on biodiversity, but there is still need to better understand the proximate causes of its predation. Based on a citizen science project, we assessed the role of spatiotemporal (i.e., latitude, longitude and seasons), climatic (i.e., rainfall), anthropogenic (i.e., human footprint, HFI) and individual (i.e., sex and age) variables on the number of preys returned home by cats in metropolitan France. Over the 5 048 cats monitored between 2015 and 2022, prey from 12 different classes (n= 36 568) were returned, being 68% mammals, 21% birds and 8% squamates. Shrews brought home by cats peaked during summer, while rodents were recorded during summer-autumn. Birds brought home by cats peaked in spring-summer and in autumn, and lizards in spring and in late summer. Lower HFI was associated with more voles and mice brought home and the opposite trend was observed for lizards and birds. Younger cats were more prone to bring home shrews, birds and reptiles. Although environmental factors play a minor role in prey brought home by cats, some geographical characteristics of prey species distribution partly explains the hunting behaviour of cats.

This study aims at providing a systematic and critical review on the state-of-the-art of life cycle applications from the circular economy point of view. In particular, the main objective is to un-derstand how researchers adapt life cycle approaches for the measurement of the empirical cir-cular pathways of agri-food systems along the overall lifespan. To perform the literature review, PRISMA protocol was considered to conduct a review by qualitative synthesis. Specifically, an evaluation matrix has been set up to gather and synthesize research evidence, by classifying pa-pers according to several integrated criteria. The literature search was carried out employing scientific databases. Findings evidence that the most common circularity topics are about closed-loop production systems, i.e. nutrient recovery for agricultural purposes, production of renewable energy, valorization of residues and wastes as fertilizers, food waste, and agro-wastes recycling for agriculture. To evaluate the benefits/impacts of CE strategies, Life Cycle Assess-ment (LCA) proved to be the most common methodology applied by authors, as it can help to meet the main CE requirements slowing and closing resource loops.

There is growing awareness that “Nature-based Solutions” (NbS) can help to protect us from climate change impacts whilst slowing further warming, supporting biodiversity and securing ecosystem services. However, the potential of NbS to provide the intended benefits has not been rigorously assessed. There are concerns over their reliability and cost-effectiveness compared to engineered alternatives, and their resilience to climate change. Trade-offs can arise if climate mitigation policy encourages NbS with low biodiversity value, such as afforestation with non-native monocultures. This can result in maladaptation, especially in a rapidly changing world where biodiversity-based resilience and multifunctional landscapes are key. Here we highlight the rise of NbS in climate policy—focussing on their potential for climate change adaptation as well as mitigation—and discuss barriers to their evidence-based implementation. We outline the major financial and governance challenges to implementing NbS at scale, highlighting avenues for further research. As climate policy turns increasingly towards greenhouse gas removal approaches such as afforestation, we stress the urgent need for natural and social scientists to engage with policymakers. They must ensure that NbS can achieve their potential to tackle both the climate and biodiversity crisis while also contributing to sustainable development. This will require systemic change in the way we conduct research and run our institutions.

The constant increase in current density in electrical wires leads to increasingly significant heat losses due to Joule effect. Therefore, reducing the electrical resistivity of copper wires becomes necessary. To achieve this goal, the development of a composite material incorporating a more conductive reinforcement, the graphene, is a promising way. The design of a copper/graphene composite using a powder metallurgy-based method is presented. This synthesis method allows for interface control through the growth of CuO(Cu) nanoparticles tightly bonded to the reinforcement. It also involves the dispersion of graphene through ultrasonic treatment and its alignment within the matrix using a uniaxial pressing densification method. The increase in the hardness (+12 HV) demonstrates the effective dispersion and separation of graphene layers. The impact on the electrical properties of dendritic copper (ρe = 2.30 µΩ.cm) remains limited, with a decrease in electrical resistance of approximately 1.4%. However, for copper with higher electrical resistivity, flake copper (at 2.71 µΩ.cm) and brass at (7.66 µΩ.cm), reductions of 2.7% and 10% have been achieved, respectively. With the improvement of graphene quality, there is more room to improve the electrical properties. This work paves the way for the development of composites with improved electrical resistivity.

Increased levels of insecticide resistance in major malaria vectors such as Anopheles funestus threaten the effectiveness of insecticide-based control programmes. Understanding the landscape features impacting the spread of resistance makers is necessary to design suitable resistance management strategies. Here we examined the influence of the highest mountain in West Africa (Mount Cameroon; 4,100 meters elevation) on the spread of metabolic and target-site resistance alleles in An. funestus populations. Vector composition varied across the four localities surveyed along the altitudinal cline with major vectors exhibiting high parity rate (80.5%). Plasmodium infection rates ranged from 0.79% (An. melas) to 4.67% (An. funestus). High frequencies of GSTe2R (67% - 81%) and RdlR (49% - 90%) resistance alleles were observed in An. funestus throughout the study area, with GSTe2R frequency increasing with altitude whereas the opposite is observed for RdlR. Patterns of genetic diversity and population structure analyses revealed high levels of polymorphisms with 12 and 16 haplotypes respectively for GSTe2 and Rdl. However, the reduced diversity patterns of resistance allele carriers revealed signatures of positive selection on the two genes across the study area irrespective of the altitude. Despite slight variations associated with the altitude, the spread of resistance alleles suggest that control strategies could be implemented against malaria vectors across mountainous landscapes.

Health of migrant is a widely studied topic. It has been argued that migrant health may deteriorate over time. Though migrants are ‘a hard to reach’ population in survey data, this paper builds on a unique dataset provided by Médecins du Monde from five countries. We study self perceived health (SPH) in connection with socio-economic and demographic factors and length of stay. Results show different results for men and women. Asylum seekers compared to other documented migrants have a worse health. Migrants with better living conditions tend to be in better health. Employment and stable accommodation has a positive effect on SPH. Women from poorer countries have a better physical SPH after 3 months of residing in the host country. This paper contributes widely to knowledge of health of migrants. Contrarily to other evidence, health of migrants tends to improve for some migrants.

Fired bricks have shown tremendous potential as a construction material due to their properties. However, their use required some specifications in terms of quality, resistance, and durability. In developing countries, the lack of tools to make test specimens leads to many defects in these brick specimens responsible for low durability and weak precision during mechanical tests and shrinkage. In this study, a simple and traditional method of making test bricks is presented. This simple method allows the production of bricks with the required properties. This method is especially efficient for a firm or semi-soft pastes consistency. The handmade pastes do not stick into the walls of the mold like the case of steel molds and it gives specimens with standard shape, smooth surface, and sharp edges. The resulting fired bricks exhibit high mechanical strength comparable and even better than those of conventional methods.

Although the most common forms of brain injury in preterm infants have been associated with adverse neurodevelopmental outcomes, existing MRI scoring systems lack specificity, do not incorporate clinical factors, and are technically challenging to perform. The objective of this study was to develop a web-based, clinically-focused prediction system which differentiates severe from normal-moderate neurodevelopmental outcomes at two years. Infants were retrospectively identified as those who were born ≤30 weeks gestation, had MR imaging at term-equivalent age, and neurodevelopmental testing at 18-24 months. Each MRI was scored on injury in three domains (intraventricular hemorrhage, white matter injury, and cerebellar hemorrhage) and clinical factors strongly predictive of outcome were investigated. A binary logistic regression model was then generated from the composite of clinical and imaging components. A total of 154 infants were included (mean GA = 26.1±1.8 weeks, BW = 889.1±226.2 grams). The final model (imaging score + ventilator days + delivery mode + antenatal steroids + ROP requiring surgery) had strong discriminatory power for severe disability (AUC=0.850), with a PPV of 76% and NPV of 90%. Available as a web-based tool, it can be useful for prognostication and targeting early intervention services to infants who may benefit most from such services.

This study aimed to characterize the long non-coding RNA (lncRNA) expression in the bovine mammary gland and to infer their functions in dietary response to 5% linseed oil (LSO) or 5% safflower oil (SFO). Twelve cows (six per treatment) in mid lactation were fed a control diet for 28 days followed by a treatment period (control diet supplemented with 5% LSO or 5% SFO) of 28 days. Mammary gland biopsies were collected from each animal on day-14 (D-14, control period), D+7 (early treatment period) and D+28 (late treatment period) and were subjected to RNA-Sequencing and subsequent bioinformatics analyses. Functional enrichment of lncRNA was performed via potential cis regulated target genes located within 50 Kb flanking regions of lncRNAs and having expression correlation of >0.7 with mRNAs. A total of 4955 lncRNAs (325 known and 4630 novel) were identified which potentially cis targeted 59 and 494 genes in LSO and SFO treatments, respectively. Enrichments of cis target genes of lncRNAs indicated potential roles of lncRNAs in immune function, nucleic acid metabolism and cell membrane organization processes as well as involvement in Notch, cAMP and TGF-β signaling pathways. Thirty-two and 21 lncRNAs were differentially expressed (DE) in LSO and SFO treatments, respectively. Six genes (KCNF1, STARD13, BCL6, NXPE2, HHIPL2 and MMD) were identified as potential cis target genes of six DE lncRNAs. In conclusion, this study indicated potential roles for lncRNAs in mammary gland immune functions and development and provided potential candidate genes and pathways via which lncRNAs can function in diet responses.

The current focus on afforestation in climate policy runs the risk of compromising both longterm carbon storage and human adaptation. It also works against efforts to stem the tide of biodiversity loss. We outline why an emphasis on diverse, intact natural ecosystems—as opposed to tree plantations with fast-growing exotic species—will help nations deliver the goals of the Paris Agreement and much more.

Conjunctival melanoma (Co-M) is an aggressive, invasive eye and eyelid cancer. Its global inci-dence of ~1 in a million is increasing at a rate ratio of ~1.4, but this rises sharply in over 65-year-olds. Although rare, Co-M has a devastating impact on the lives of those who develop it. Co-M is often misdiagnosed or overlooked leading to vision loss either from destructive effects of the tumour or side effects of therapy, facial disfigurement from radical surgery, and death from metastases. Due to its rarity, there is limited evidence for diagnosis and management; hence, there is no standardised treatment and not all cases are referred to a specialised ocular oncology centre. Recent progress in cancer immunology and genetics have revolutionised treatment of cutaneous melanoma, which share some similarities to Co-M. A better understanding of Co-M and its precursor lesions is urgently needed to lead the development of novel targeted and immuno-therapies both for local tumour control and disseminated disease. This review aims to provide a comprehensive clinical overview of the current knowledge of Co-M, its epidemiology, pathogenesis, presentation, diagnosis, management, and recent advances in novel biological therapies for personalised treatment of this disease.

Optical switching is an essential part of photonic integrated circuits and the focus of research at the moment. In this research, an optical switch design working on the phenomenon of the guided-mode resonances in 3D photonic crystals-based structure is reported. The optical-switching mechanism is studied in a dielectric slab-waveguide-based structure operating in the near-infrared range in a telecom window of 1.55 µm. The mechanism is investigated by interference of two signals, i.e., the data signal and the control signal. The data signal is coupled into the optical structure and filtered utilizing guided-mode resonance, whereas, the control signal is index guided in the optical structure. The amplification or de-amplification of the data signal is controlled by tuning the spectral properties of the optical sources and structural parameters of the device. The parameters are optimized first using a single-cell model with periodic boundary conditions and later in a finite 3D-FDTD model of the device. The numerical design is computed in an open-source Finite Difference Time Domain simulation platform. Optical amplification in the range of 13.75 % is achieved in the data signal with a decrease in the linewidth up to 0.0079 µm and a quality factor of 114.58. The proposed device presents great potential in the field of photonic integrated circuits, biomedical technology, and programmable photonics.

Smart city infrastructure has a significant impact on improving the quality of humans life. However, a substantial increase in the urban population from the last few years is posing challenges related to resource management, safety, and security. In order to ensure safe mobility and security in the smart city environment, this paper proposes a novel Artificial Intelligence (AI) based approach empowering the authorities to better visualize the threats and to help them identify the highly-reported crime zones yielding greater predictability of crime hot-spots in a smart city. To this end, it first investigates the Hierarchical Density-Based Spatial Clustering of Applications with Noise (HDBSCAN) to detect the hot-spots that have a higher risk of crimes to be committed. Second, for crime prediction, Seasonal Auto-Regressive Integrated Moving Average (SARIMA) exploited in each dense crime region to predict the number of crimes in the future with spatial and temporal information. The proposed HDBSCAN and SARIMA based crime prediction model is evaluated on ten years of crime data (2008-2017) for New York City (NYC). The accuracy of the model is measured by considering different time period scenarios i.e. (a) year-wise, i.e., for each year and (b) for the whole period of ten years, using an 80:20 ratio where 80\% data was used for training and 20\% data was used for testing. The proposed approach outperforms with an average Mean Absolute Error (MAE) of 11.47.

Nature-based solutions (NbS) are increasingly recognised for their potential to address both the climate and biodiversity crises. These outcomes are interdependent, and both rely on the capacity of NbS to support and enhance the health of an ecosystem: its biodiversity, the condition of its abiotic and biotic elements, and its capacity to function normally despite environmental change. However, while understanding of ecosystem health outcomes of nature-based interventions for climate change mitigation is growing, the outcomes of those implemented for adaptation remain poorly understood with evidence scattered across multiple disciplines. To address this, we conducted a systematic review of the outcomes of 109 nature-based interventions for climate change adaptation using 33 indicators of ecosystem health across eight broad categories (e.g. diversity, biomass, ecosystem functioning and population dynamics). We showed that 88% of interventions with positive outcomes for climate change adaptation also reported measurable benefits for ecosystem health. We also showed that interventions were associated with a 67% average increase in local species richness. All eight studies that reported benefits in terms of both climate change mitigation and adaptation also supported ecosystem health, leading to a triple win. However, there were also trade-offs, mainly for forest management and creation of novel ecosystems such as monoculture plantations of non-native species. Our review highlights two major limitations of research to date. First, only a limited selection of metrics are used to assess ecosystem health and these rarely include key aspects such as functional diversity and habitat connectivity. Second, taxonomic coverage is poor: 67% of outcomes assessed only plants and 57% did not distinguish between native and non-native species. Future research addressing these issues will allow the design and adaptive management of NbS to support healthy and resilient ecosystems, and thereby enhance their effectiveness for meeting both climate and biodiversity targets.

The Black Steel slag (Ss) and phosphogypsum (PG) are industrial wastes produced in Morocco. In order to reduce these two wastes and to evaluate their pozzolanic reactivity in the presence of water, they were incorporated into bentonite (B) mixed with lime (L). The studied mixtures (BLW, BL-PG-W and BL-PG-Ss-W) were analyzed by X-ray diffraction, Infrared spectroscopy, Raman spectroscopy and SEM/EDX analysis. Compressive strength tests were performed on hardened specimens. The results obtained show that the hydration kinetics of the B-L-W and B-L-PG-W mixtures are slow. The addition of PG to a bentonite-lime mixture induces the formation of new microstructures such as hydrated calcium silicate (C-S-H) and ettringite, which increases the compressive strength of the cementitious specimens. The addition of the Ss to a mixture composed by 8%PG and 8%L-B accelerates the kinetics of hydration and activates the pozzolanic reaction. The presence of C2S in the slag helps to increase the mechanical strength of the mixture B-L-PG-Ss. The compressive strength of the mixtures BL-W, BL-PG-W and BL-PG-Ss-W increases from 15 to 28 days of setting. After 28 days of setting, 8% of Sc added to the mixture 8% PG-8%L-B is responsible for an increase of the compressive strength to 0.6 MPa.

Sideroflexins (SLC56 family) are highly conserved multi-spanning transmembrane proteins inserted in the inner mitochondrial membrane in eukaryotes. Few data are available on their molecular function but, since their first description, they were thought to be metabolite transporters probably required for iron utilization inside the mitochondrion. Such as numerous mitochondrial transporters, sideroflexins remain poorly characterized. The prototypic member SFXN1 has been recently identified as the previously unknown mitochondrial transporter of serine. Nevertheless, pending questions on the molecular function of sideroflexins remain unsolved, especially their link with iron metabolism. Here, we review the current knowledge on sideroflexins, their presumed mitochondrial functions and the sparse - but growing - evidence linking sideroflexins to iron homeostasis and iron-sulfur cluster biogenesis. Since an imbalance in iron homeostasis can be detrimental at the cellular and organismal levels, we also investigate the relationship between sideroflexins, iron and physiological disorders. Investigating Sideroflexins’ functions constitutes an emerging research field of great interest and will certainly lead to main discoveries on mitochondrial physiopathology.

Prevalence of malnutrition among children under five is alarmingly high in Pakistan. However, there are ready-to-use therapeutic foods (RUTF) available which may be used to treat children with severe acute malnutrition (SAM). This study aims to assess the efficacy of prebiotics as a synergistic additive to RUTF to enhance blood parameters and anthropometric measurements in children with uncomplicated SAM living in Southern Punjab, Pakistan. A double-blind parallel treatment randomized controlled trial was conducted on 204 children aged between 6-59 months. Participants were randomized and allocated to the placebo (n=102) and experimental arms (n=102) at a 1:1 ratio. One group of children were provided RUTF and 4 g prebiotics, while the other group were given RUTF and starch as a placebo. Participants recruited for both arms were given treatment for eight weeks, and then their biochemical and anthropometric outcomes were evaluated. A substantial difference between the mean weight, mid upper arm circumference, haemoglobin, haematocrit, platelet count, mean corpuscular volume, mean corpuscular haemoglobin, and albumin was revealed. Conclusively, supplementation with RUTF and prebiotics has proven to be an efficient, effective and safe therapy for children suffering from SAM to improve their growth and development indicators and reduce the dangers of malnutrition in comparison to RUTF alone.

Influenza virus transcription is catalyzed by the viral RNA-polymerase (FluPol) through a cap-snatching activity. The snatching of the cap of cellular mRNA by FluPol is preceded by its binding to the flexible C-terminal domain (CTD) of the RPB1 subunit of RNA-polymerase II (Pol II). To better understand how FluPol brings the 3’-end of the genomic RNAs in close proximity to the host-derived primer, we hypothesized that FluPol may recognize additional Pol II subunits/domains to ensure cap-snatching. Using binary complementation assays between the Pol II and FluPol subunits and their structural domains, we revealed an interaction between the N-third domain of PB2 and RPB4. This interaction was confirmed by a co-immunoprecipitation assay and found to occur with the homologous domains of influenza B and C FluPols. Residues [1-72] of RPB4 were found critical in this interaction. Numerous punctual mutants generated at conserved positions between influenza A, B and C FluPols in the N-third domain of PB2 exhibited strong transcriptional activity defect. These results suggest that FluPol interacts with several domains/subunits of Pol II, the CTD to bind Pol II initiating host transcription and a second on RPB4 to locate FluPol at the proximity of the 5’-end of nascent host mRNA.

Duchenne muscular dystrophy (DMD) is a yet incurable rare genetic disease that affects the skeletal and cardiac muscles, leading to progressive muscle wasting and premature death. DMD is caused by the lack of dystrophin, a muscle protein essential for the biochemical support and integrity of muscle fibers. Gene replacement strategies for Duchenne muscular dystrophy (DMD) employing the adeno-associated virus (AAV) face the challenge imposed by the limited packaging capacity of AAV, only allowing the accommodation of a short version of dystrophin (µDys) that is still far removed from correcting human disease. The need to develop strategies leading to the expression of a best performing dystrophin variant led to only few studies reporting on the use of dual vectors, but none reported on a method to assess in vivo transgene reconstitution efficiency, the degree of which directly affects the use of safe AAV dosing. We report here on the generation of a dual AAV vector approach for the expression of a larger dystrophin version (quasidystrophin) based on homologous recombination, and the development of a methodology employing a strategic droplet digital PCR design, to determine the recombination efficiency as well as the occurrence of unwanted concatemerization events or aberrant expression from the single vectors. We demonstrated that, upon systemic delivery in the dystrophic DBA2mdx mice, our dual AAV approach led to high transgene reconstitution efficiency and negligible ITR-dependent concatemerization, with consequent remarkable protein restoration in muscles and improvement of muscle pathology. This evidence supports the suitability of our system for gene therapy application and the potential of this methodology to assess and improve the feasibility for therapeutic translation of multiple vector approaches

The latest developments in digital humanities have increasingly enabled the construction of large data sets which can easily be accessed and used. These data sets often contain indirect localisation information, such as historical addresses. Historical geocoding is the process of transforming the indirect localisation information to direct localisation that can be placed on a map, which enables spatial analysis and cross-referencing. Many efficient geocoders exist for current addresses, but they do not deal with temporal information and are usually based on a strict hierarchy (country, city, street, house number, etc.) that is hard, if not impossible, to use with historical data. Indeed, historical data are full of uncertainties (temporal, textual, positional accuracy, confidence in historical sources) that can not be ignored or entirely resolved. We propose an open source, open data, extensible solution for geocoding that is based on gazetteers composed of geohistorical objects extracted from historical topographical maps. Once the gazetteers are available, geocoding an historical address is a matter of finding the geohistorical object in the gazetteers that is the best match to the historical address searched by the user. The matching criteria are customisable and include several dimensions (fuzzy string, fuzzy temporal, level of detail, positional accuracy). As the goal is to facilitate historical work, we also propose web-based user interfaces that help geocode (one address or batch mode) and display over current or historical topographical maps, so that geocoding results can be checked and collaboratively edited. The system has been tested on the city of Paris, France, for the 19th and the 20th centuries. It shows high response rates and is fast enough to be used interactively.

Forensic anthropologists play a key role in skeletal trauma analysis and commonly use macroscopic features to distinguish between trauma types. However, this approach can be challenging, particularly in cases of highly comminuted or incompletely recovered fractures. Histological analysis of microscopic fracture characteristics in fractured bones may thus help provide additional information on trauma type and bone fracture biomechanics in general. This study analysed the extent of microcrack damage to osteons in long bones with blunt force trauma (BFT) and gunshot trauma (GST), from both traumatic death cases and post-mortem experimental fractures. We identified four types of osteonal damage (OD). In traumatic death cases, OD affecting the inside of the osteon and compromising the Haversian canal (type 1) was found to be indicative of BFT. Moreover, OD affecting the cement line (type 3) and interstitial lamellae (type 4) was more common in the GST samples. OD affecting the inside of the osteon without compromising the Haversian canal (type 2) was not found to be indicative of either trauma type. In cases of experimental fractures, our study revealed that post-mortem fractures in dry bone samples featured the highest amount of OD, particularly of type 4. This study also found that the experimentally produced GST featured similar OD pattern to GST death cases. These findings support our hypothesis that there are distinct osteonal damage patterns in human long bones with BFT and GST, which are of relevant value for trauma analysis in forensic anthropology.

Two peat cores from two bogs were used to reconstruct high–resolution changes in atmospheric Pb accumulation rate (Pb AR) in Belgium during the Roman period. The two records were compared to assess the reliability of peat cores as archives of atmospheric Pb deposition and to established histories of atmospheric emissions from anthropogenic sources. To address these issues we analyze Pb concentration and isotopes, using ICP-MS, LA-ICP-MS and MC-ICP-MS in two peat sections, spanning 1000 yr each. Lead concentrations in the two cores range from 0.1 to 60 μg g⁻¹, with the maxima between 15 and 60 μg g⁻¹. The average natural background of Pb AR was 0.005± 0.002 mg m^-2 yr^-1 and the maximum ranges from 0.7 to 1.2 mg m^-2 yr^-1 between 50 BC and AD 215. The highest Pb AR exceed the pre-Roman period values by a factor of 25-30. Pb isotopic composition indicates that mining and metallurgical activities were the predominant sources of pollution during the Roman period. The Pb AR and chronologies in the Belgian peat cores are consistent with those reported for other continental archives as lake sediments, peat and ice cores.

Silybum marianum L. is a well-known medicinal herb, primarily used in liver protection. Light strongly affects several physiological processes along with secondary metabolites biosynthesis in plants. Herein, S. marianum was exploited for in vitro potential under different light regimes in the presence of melatonin. The optimum callogenic response occurred in combination of 1.0 mg/L α-naphthalene acetic acid and 0.5 mg/L 6-Benzylaminopurine under photoperiod. Continuous light associated with melatonin treatment increased total flavonoid content (TFC), total phenolic content (TPC) and antioxidant potential, followed by photoperiod and dark treatments. The increased level of melatonin has a synergistic effect on biomass accumulation under continuous light and photoperiod, while adverse effect was observed under dark condition. More detailed phytochemical analysis showed maximum total silymarin content (11.92 mg/g DW) when placed under continuous light + 1.0 mg/L melatonin. Individually, the level of silybins (A and B), silydianin, isolsilychristin and silychristin was found highest under continuous light. Anti-inflammatory activities were also studied and highest percent inhibition was recorded against 15-LOX for cultures cultivated under continuous light (42.33%). The current study helps to better understand the influence of melatonin and different light regimes on silymarin production as well as antioxidant and anti-inflammatory activities in S. marianum callus extracts.

The study assessed the impact of different diets on gastrointestinal pH, intestinal microbiota, digestive tract morphometry, and productive performance in guinea pigs. A total of 160 improved genotype guinea pigs were used, distributed into three groups with different diets: alfalfa (T1), alfalfa + concentrate (T2), and concentrate (T3), to which a mixture of probiotics combined with vitamins, minerals was added and amino acids in T2 and T3. Gastrointestinal pH showed significant differences between treatments in the various segments of the digestive tract. The intestinal microbiota varied according to the diet, with Escherichia coli being the predominant bacterium in weaned guinea pigs. Intestinal morphometry was significantly altered with the addition of a reinforced probiotic mixture, improving the length and density of intestinal villi. Productive parameters such as weight gain, feed consumption, and feed conversion were better in guinea pigs fed a mixed diet with 0.5% probiotic mixture. These results indicate that intestinal pH may influence microbial composition, which impacts productive efficiency and immune health, highlighting the importance of balanced nutrition and supplementation to optimize the health and performance of guinea pigs.

Bismuth sodium titanate thin films (BNT) were deposited on Pt/SiN substrates by Sol-Gel spin coating technique under O2 atmosphere. Microstructural, structural, and electrical properties of the obtained film were investigated. Scanning electron microscopy and atomic force microscopy micrographs were used to analyze the microstructure of the films. Furthermore, EDX analysis revealed a Na-deficient composition for the obtained film. X-ray diffraction and Raman spectroscopy allowed the identification of a pure perovskite BNT phase. Dielectric, ferroelectric, and leakage current measurements revealed good frequency stability of the dielectric constant and dielectric losses for BNT thin film. The results are discussed in terms of Na-deficiency effects on the defect structure of BNT. Further, the film showed attractive electrostatic energy storage properties with energy density that exceeds 1.04 J/cm3 under E = 630 kV/cm.

Considering the increasing interest in understanding the biotic component of methane removal from our atmosphere, it becomes essential to study the physiological characteristics and genomic potential of methanotroph isolates, especially their traits allowing them to adapt to elevated growth temperatures. The genetic signatures of Methylocaldum species have been detected in many terrestrial and aquatic ecosystems. A small set of representatives of this genus has been isolated and maintained in culture. The genus is commonly described as moderately thermophilic, with the growth optimum reaching 50oC for some strains. Here, we present a comparative analysis of genomes of three Methylocaldum strains—two terrestrial M. szegediense strains (O-12 and Norfolk) and one marine strain Methylocaldum marinum (S8). The examination of the core genome inventory of this genus uncovers significant redundancy in primary metabolic pathways, including the machinery for methane oxidation (numerous copies of pmo genes) and methanol oxidation (duplications of mxaF, xoxF1-5 genes), three pathways for one-carbon (C1) assimilation, and two methods of carbon storage (glycogen and polyhydroxyalkanoates). We also investigate the genetics of melanin production pathways, as a key feature of the genus.

Myocardial heterogeneity is an attribute of the normal heart. We have developed integrative models of cardiomyocytes from the subendocardial (ENDO) and subepicardial (EPI) ventricular regions that take into account experimental data on specific features of intracellular electromechanical coupling in the guinea pig heart. The models adequately simulate experimental data on the action potential and contraction of the ENDO and EPI cells. The modeling results predict that heterogeneity in the parameters of calcium handling and myofilament mechanics in isolated ENDO and EPI cardiomyocytes via cooperative mechanisms of mechano-calcium-electric feedback are essential to produce the differences in Ca²⁺ transients and contraction profiles and may further enhance transmural differences in the electrical properties between the cells. Simulation results predict that ENDO cells have greater sensitivity to changes in afterload than EPI cells. These data are important for understanding the behavior of cardiomyocytes in the intact heart.

Background: Lithium di-silicate dental ceramics bonding, realized by using different resins, is strictly dependent on micro-mechanical retention and chemical adhesion. The aim of this in vitro study was to investigate the capability of a 1070 nm fiber laser for their surface treatment. Methods: Samples were irradiated by a pulsed fiber laser at 1070 nm with different parameters (Peak Power from 5 kW to 5 kW, RR 20 kHz, speed from 10 to 50 mm/s, total Energy Density from 1.3 to 27 kW/cm²) and the thermal elevation during the experiment was recorded by a Fiber Bragg Grating (FBG) temperature sensor. Subsequently, the surface modifications were analysed by optical microscope, Scanning Electron Microscope (SEM) and Energy Dispersive X-ray Spectroscopy (EDS). Results: With a Peak Power of 5 kW, RR of 20 kHz and speed of 50 mm/s, the microscopic observation of the irradiated surface showed increased roughness with small areas of melting and carbonization. EDS analysis revealed that, with these parameters, there are no evident differences between laser-processed samples and controls. Thermal elevation during laser irradiation ranged between 5 °C and 9 °C. Conclusions: 1070 nm fiber laser can be considered as a good device to increase the adhesion of Lithium di-silicate ceramics.

: Healthcare workers are affected by mental health issues, burnout and turnover, and this burden is even greater during epidemics and pandemics, such as COVID-19. The purpose of this research is to provide an overview of the measures introduced or supported in the institutions of Quebec’s health and social services network during the COVID-19 pandemic with the aim of protecting healthcare workers’ mental health. An online questionnaire survey was administered in 2021 among human resources department personnel in health and social services network institutions involved in workplace mental health in Quebec. A total of 223 key informants representing 31 of the 34 public health and social services institutions in the province of Quebec in Canada responded to the questionnaire. Measures that focus on the needs of staff, involve all levels of authority and the ones that provide flexibility, support and recognition at work were more successful, according to the advisors surveyed. Future research into whether the same measures are considered effective or ineffective outside of a pandemic context is needed.

Introduction: Diclofenac is the most prescribed non-steroidal anti-inflammatory drug worldwide and used to reliev pain and inflammation for inflammatory arthritis. Diclofenac do not slows disease progression and cartialge damage of Rheuamtoid Arthritis individuals. Moreover, it associated with seriuos adverse effects even using regular dose regimens. Drug delivery systems can overcome this issues reducing adverse effects and optmizing efficacy. Objectives: to evaluate the activity of a lipid-core nanocapsule loaded of Diclofenac (DIC-LNC) in an experimental model of adjuvant-induced arthritis and its anti-arthritic properties at the joint components. Methods: The diclofenac nanoformulation was obtained by self-assembling methodology. The stereology analysis aproach was applied for morphological quantification of the volume, density and cellular profile count of the metatarsophalangeal joints of rats induced to adjuvant arthritis. Proinflamatory cytokines and biochemical profile was also obtained. Results: DIC-LNC is able to reduce arthitis compared to control group (p<0.0001) and DIC group (p=0.009). The TNF and IL1 cytokine as well as C-reative protein and Xanthine-oxidade were efficiently reduced by DIC-LNC. Additionally, DIC-LNC reduces synovites and condrocytes lossing compared to DIC (p<0.05)and control group (p<0.05). The synovial space volume was higher for DIC-LNC compared to DIC (p<0.05) and Control (p<0.05). These data are suggesting that DIC-LNC is showing anti-arthritic actvity preserving deep joint components. Conclusion: DIC-LNC is a promissing nanoformulation for clinical use, since is able to reduce joint inflamation and synovits, avoiding damage of cartilage and synovial space at advjuvant athrits. Further studies and developments are necessary to achieve future clinical use.

Nature-based solutions (NbS) - working with and enhancing nature to address societal challenges - are increasingly being featured in climate change adaptation policy and plans. While there is growing evidence that NbS can reduce vulnerability to climate change impacts in general, there is a lack of understanding on the mechanisms through which this can be achieved, particularly in the Global South. To address this, we analyse 85 nature-based interventions in rural areas across the Global South, and factors mediating their effectiveness, based on a systematic map of peer-reviewed studies encompassing a wide diversity of ecosystems, climate impacts, and intervention types. We develop and apply an analytical framework of people’s social-ecological vulnerability to climate change, in terms of six pathways of vulnerability reduction: social and ecological exposure, sensitivity, and adaptive capacity. Most cases (95%) report a reduction in vulnerability, primarily by lowering ecosystem sensitivity to climate impacts (73% of interventions), followed by reducing social sensitivity (52%), reducing ecological exposure (36%), increasing social adaptive capacity (31%), increasing ecological adaptive capacity (19%) and/or reducing social exposure (14%). An analysis of mediating factors shows that social dimensions are equally important as technical factors in NbS to achieving equitable and effective outcomes. Attention to the distinct social and ecological pathways through which vulnerability is reduced helps to harness the multiple benefits of working with nature in a warming world.

Reactions of Fe(II) with the tris-(pyridin-2-yl)ethoxymethane (py3C-OEt) tripodal ligand in presence of the pseudohalide ancillary NCE- (E = S, Se, BH3) ligands led to a series of three mononuclear complexes formulated as [Fe(py3C-OEt)2][Fe(py3C-OEt)(NCE)3]2·2CH3CN, with E = S (1), BH3 (2) and Se (3). Single crystal characterizations (complexes 1-2) and X-ray powder diffraction (complexes 1-3) reveal monomeric isomorph structures formed by the spin crossover (SCO) anionic [Fe(py3C-OEt)(NCE)3] complex, associated with the low spin (LS) cationic [Fe(py3C-OEt)2]2+ complex and two solvent acetonitrile molecules. In the [Fe(py3C-OEt)2]2+ cation, the Fe(II) is coordinated by two py3C-OEt tridentate ligands, while the [Fe(py3C-OEt)(NCE)3] anion displays a hexacoordinated environment involving three N-donor atoms of one py3C-OEt ligand and three nitrogen atoms arising from of the three (NCE) coligands. The magnetic studies show the presence of gradual SCO behavior for the three complexes: a one-step transition around 205 K for 1 and two step-transitions for compounds 2 and 3, centred at 245 K and 380 K for 2, and at 170 K and 298 K for 3. The magnetic behaviors of complexes 1 and 2 remain unchanged when heating up to 500 K, while complex 3 shows significant changes which are caused by the crystallisation solvent loss above room temperature.

Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease that develops in neonates as a consequence of preterm birth and arrested fetal lung development. The incidence of BPD remains on the rise, as a result of increasing survival of extremely preterm infants. Severe BPD contributes to significant health care costs and is associated with prolonged hospitalizations, respiratory infections, and neurodevelopmental deficits. In this study, we aimed to detect novel biomarkers of severe BPD. We collected tracheal aspirates (TA) from preterm babies with mild/moderate (n = 8) and severe (n = 17) BPD, and we profiled the expression of 1048 miRNAs using a PCR array. Associations with biological pathways were determined with the Ingenuity Pathway Analysis (IPA) software. We found 31 miRNAs differentially expressed between the two disease groups (2-fold change, FDR &lt; 0.05). Of these, 4 miRNAs displayed significantly higher expression levels, and 27 miRNAs had significantly lower expression levels in the severe BPD vs. the mild/moderate BPD group. IPA identified cell signaling and inflammation pathways associated with miRNA signatures. We conclude that TAs of extreme premature infants contain miRNA signatures associated with severe BPD. These signatures may serve as biomarkers of disease severity in infants with BPD.

The interplay between the human gut microbiota and the peripheral immune system significantly affects the efficacy of immune checkpoint inhibitors (ICIs) in cancer therapy. Despite this profound connection, the practical implications of microbiota dysbiosis in cancer immunotherapy ICIs & and CAR-T remain intricate and poorly understood in practical terms. This paper offers a comprehensive review of current literature on the role of gut microbiota dysbiosis in tumor development, and emerging microbiota modulation interventions, with a focus on fecal microbiota transplantation (FMT). FMT is a cost-effective therapeutic avenue, particularly in addressing diseases rooted in antibiotic-resistant bacteria, such as Clostridium difficile. Here we provided insights into the applications of FMT and other gut microbiota therapies in the landscape of cancer treatment, emphasizing their influence on the tumor microenvironment and the efficacy of ICIs with suggestions for future research directions and their implications for clinical practice.

Orb web spiders are common and highly diversified animals found in almost all habitats. They have remarkable plasticity against biotic and abiotic factors, making them excellent indicators of environmental health. The web-creation behavior of spiders is influenced by disturbances in the environment. The aim of the research was to observe the alteration in the web-building behavior of Neoscona vigilans caused by human activities, specifically traffic disturbance. Spider webs were located and photographed at nighttime along the roadside, and their web characteristics were calculated. Spiders were captured from webs for their body measurements. Spider 4^th leg length, carapace width, and body length had a significant association with web size and diameter, CTL, capture area, and mesh size. The quantity of trapped prey, the height of the plant, and the foliage radius increased with the distance from the road. Conversely, anchor points and web elevation from the ground dropped. The highest and lowest proportion of anomalies (modifications/defects) were recorded as holes (52.7%) in 105 webs (100%) and supernumerary (0.7%) in 55 webs (52.4%), respectively. Road disturbance had a negative influence on the spider’s behavior as the webs formed in close proximity to the road had a higher frequency of anomalies with a gradual decrease distantly. We can gain further insight into how different environmental changes, disruptions, and pollutants lead to this imperfection in the otherwise flawless perfect structure of spider webs.

Bi0.5Na0.5TiO3-0.06BaTiO3 (BNT-BT) thin films were prepared by both chemical solution (CSD) and pulsed laser deposition (PLD). The microstructure, dielectric, and ferroelectric properties were investigated. High stability of the dielectric permittivity (∆ɛ/ɛ(150 °C) ≤ ± 15%) over a wide temperature range from room temperature to 300 °C was obtained. Distinctly, the CSD film showed high TCC stability with variation of ± 5% up to 250°C. Furthermore, the CSD film showed an unsaturated ferroelectric hysteresis loop characteristic of the ergodic relaxor phase, however the PLD one exhibited almost saturated loop signature of the coexistence of both ergodic and non-ergodic states. The energy storage properties of the prepared films were determined using the P–E loops obtained at different temperatures. The results showed that these films exhibit stable and improved energy storage density comparable to the ceramic capacitors. Moreover, the CSD film exhibited more rigidity and better energy storage density that exceeds 1.3 J/cm3 under low applied field of 317 KV/cm as well as interesting efficiency in a large temperature range. The obtained results are very promising for energy storage capacitors operating at high temperatures.

Abscisic acid (ABA) plays a major role in promoting ripening in sweet cherry, a non-climateric fruit. Exogenous application of ABA has been performed to study fruit ripening and cracking, but this growth regulator is not used for commercial production. To determine the potential of this growth regulator to improve sweet cherry fruit quality, ABA canopy spraying was assayed in four cultivars. Canopy spraying of S-ABA significantly: 1) enhanced sweet cherry fruit color in ‘Glenred’, ‘Lapins’ and 'Bing' cultivars, but not in ‘Royal Rainier’ (a bi-colored cultivar), and 2) decreased fruit size and firmness in ‘Lapins’, ‘Bing’ and ‘Royal Rainier’. Seasonally reproducible effects were seen in ‘Lapins’ (mid/late-maturing) but not in ‘Glenred’ (early-maturing). Canopy spraying of nordihydroguaiaretic acid (NDGA) decreased color and increased fruit size in ‘Lapins’, but not in ‘Glenred’. Direct application of ABA on fruits attached to the tree, without application to the foliage, increased Lapins' fruit color without reducing size. These results suggest a localized fruit response to exogenous ABA application on fruit color development, but that a decrease in fruit size may be due to the effects of exogenous ABA on the tree canopy foliage.

Sideroflexins (SFXN) are evolutionarily conserved mitochondrial carriers belonging to the SCL56 family. Until recently, the metabolites transported by SFXN were unknown and they were thought to be transporters of a metabolite involved in iron homeostasis. SFXN1 is now known as the mitochondrial serine transporter. Because little is known about SFXN1 interactome, we launched a high-throughput search of SFXN1 binding partners with the aim to better understand its mitochondrial functions. Using a large-scale identification of SFXN1 physical partners based on co-immunoprecipitation followed by shotgun mass spectrometry (coIP-MS), we identified 96 putative SFXN1 interactants in the MCF7 human cell line. Our in-silico analysis of the SFXN1 interactome highlights biological processes linked to mitochondrial organization, electron transport chain and transmembrane transport. Among SFXN1 potential physical partners, ATAD3A and 17-HSD10, two proteins associated with neurological disorders and neurodegeneration, were further confirmed as interactants using different human cell lines. Further work will be needed to investigate the significance of these interactions in neurological disorders.

Ground level ozone is an abiotic stress estimated to reduce mean global annual wheat yields by nearly 10%. This study in solardomes exposed an elite cultivar, and multiple lines of synthetic wheat (primary and F2) to four levels of ozone (30 ppb, 55 ppb, 80 ppb, 110 ppb) for three months, with two lines (cv Paragon and an F2 line, BC1) selected for X-ray microcomputed tomography. The uCT imaging revealed ozone’s effect on individual grain formation, both spatially within the spike and on grain shape. Reductions in grain number occurred primarily across the middle of the spike. Grain volume reductions were driven more by reduced width and depth than reduced length. Based on yield data, both lines demonstrated relative tolerance to ozone. Links between ozone’s effects on grain morphology and grain quality are also explored. These data provide information that could be utilised in wheat breeding programmes to increase tolerance to ozone of this staple food crop.

The assessment of an organization/product's environmental footprint is based on the protocols developed by the Joint Research Centre of the European Union, which take into account 16 impact categories. Among the categories covered are toxicity to freshwater ecosystems and to humans. Standard protocols use only chemical parameters as input data, preventing the true impact of entire complex mixtures, such as emissions discharged into the environment, from being determined. Biological assays allow us to bridge this gap: in the current study, assays were used to determine baseline toxicity towards aquatic organisms (green algae, luminescent bacteria, and crustaceans) as well as specific toxicity (mutagenicity and carcinogenicity). Expected impacts were compared using two approaches (standard and bioassay-centered results obtained are not always in line and, in general, the traditional method underestimates impacts). This demonstrates the importance of these assays and suggests that they be used in LCA (Life Cycle Assessment) protocols as well.

Introduction: Congenital heart defects (CHD) are the most frequent group of major congenital anomalies, accounting for almost 1% of all births. They comprise a very heterogeneous group of birth defects in terms of their severity, clinical management, epidemiology and embryologic origins. Taking this heterogeneity into account is an important imperative to provide reliable prognostic information to patients and their caregivers, as well as to compare results between centers or to assess alternative diagnostic and treatment strategies. The Anatomic and Clinical Classification of CHD (ACC-CHD) aims to facilitate both the CHD coding process and data analysis in clinical and epidemiological studies. Objectives: 1) To describe the long-term childhood survival of newborns with CHD and 2) To develop and validate predictive models of infant mortality based on the ACC-CHD. Materials and Methods: This study is based on data from a population-based, prospective cohort study: Epidemiological Study of Children with Congenital Heart Defects (EPICARD). The final study population comprised 1881 newborns with CHD after excluding cases that were associated with chromosomal and other anomalies. Statistical analysis included non-parametric survival analysis and flexible parametric survival models. The predictive performance of models was assessed by Harrell’s C index and the Royston-Sauerbrei R2 with internal validation by bootstrap. Results: The overall 8-year survival rate for newborns with isolated CHD was 0.96 [0.93- 0.95]. There was a substantial difference between the survival rate of the categories of ACC-CHD. The highest and lowest 8-year survival rates were 0.995 [0.989-0.997] and 0.34 [0.21-0.50] for “interatrial communication abnormalities and ventricular septal defects” and "functionally univentricular heart", respectively. Model discrimination as measured by Harrell’s C was 87% and 89% for the model with ACC-CHD alone and the full model, which included other known predictors of infant mortality, respectively. The predictive performance as measured by R2 was 45% and 50%, for the ACC-CHD alone and the full model. These measures were essentially the same after internal validation by bootstrap. Conclusion: The ACC-CHD classification provided the basis of a highly discriminant survival model with good predictive ability for the 8-year survival of newborns with CHD. Prediction of individual outcomes remains an important clinical and statistical challenge.

Cathodic protection is widely used to protect metal structures from corrosion and is commonly applied on marine structures in seaports using sacrificial galvanic anodes. These anodes, either in Zinc, or preferen-tially nowadays in Al-Zn-In alloys, are expected to corrode instead of the metal to be protected. This leads to the release of specific dissolved species, Zn2+, Al3+, In3+ and solid phases like Al(OH)3. Few studies were conducted on the effects of anodes on marine organisms and concluded that further detailed investiga-tions are needed in controlled environments. We therefore propose an experimental approach to evaluate the effects of Zn and Al-Zn-In anodes on oysters stabulated in tanks, under conditions approaching those used in the ports. We chose a non-targeted metabolomic approach, using UHPLC coupled to HRMS, to study the effects on the entire metabolome, without any a priori. A modelling study of the chemical species, corresponding to the deg-radation products of the anodes, likely to be present near the exposed oysters, was also included. We identified 16 and 2 metabolites modulated by Zn- and Al-Zn-In-anodes respectively, involved in bi-ological functions, such as energy metabolism, osmoregulation, oxidative stress, lipid, nucleotide nucle-oside and amino acid metabolisms, defense and signaling pathways.

Newcastle disease virus (NDV) causes a highly contagious and devastating disease in poultry, Newcastle disease (ND). ND causes heavy economic losses to the global poultry industry by decreasing the growth rate, decrease egg productions, mortality, and morbidity. Although, significant advances have been made in the vaccine development, but outbreaks are reported in vaccinated birds leading to overall decreased growth rate. In this study, we report the damage caused by the NDV infection in the pancreatic tissues of vaccinated as well as specific pathogen free chickens. The histopathological examination of the pancreas showed sever damage in the form of partial depletion of zymogen granules, acinar cell vacuolization, necrosis, and apoptosis, congestion in the large and small vessels, sloughing of epithelial cells of pancreatic duct, and mild perivascular edema. Increased plasma levels of corticosterone, somatostatin, were observed in NDV infected chicks at 3 and 5-day post infection (DPI). Slight decrease in the plasma concentrations of the insulin were noticed at 5 DPI. Significant changes were not observed in the plasma levels of glucagon. Furthermore, NDV infection has decreases the activity and mRNA expression of amylase, lipase, and trypsin from the pancreas. Taken together, our findings highlight that NDV induces extensive tissue damage in pancreas, decrease the activity and expression of pancreatic enzymes and increase plasma corticosterone and somatostatin.

(1) Background: Most patients with mycosis fungoides (MF), a form of cutaneous T-cell lym-phoma (CTCL), develop relapsed/refractory (R/R) disease following front-line systemic therapy. This report describes treatment patterns and outcomes from the subpopulation with R/R MF. (2) Methods: This observational, retrospective, cohort study analysed patient records (1984–2016) from 27 clinical sites in Eurpe. Outcomes included treatments received, response to first-, second- and third-line treatment, overall survival (OS), and progression-free survival (PFS). (3) Results: Of 104 patients with MF, 100 received second-line and 61 received third-line therapy. Median (range) times from start of first-line therapy to first R/R MF and from first to second R/R MF were 11.2 (0.3–166.5) and 13.5 (0.0–174.6) months, respectively. Second-and third-line treatment options varied and comprised systemic therapies (85% and 79% of patients, respectively), radio-therapy (32% and 34%, respectively) and topical therapies (48% and 36%, respectively). Median (95% confidence interval [CI]) OS from the diagnosis of first R/R MF was 11.5 (6.5–not reached [NR]) years and was higher with non-chemotherapy (NR) versus chemotherapy (6.5 years); es-timated median PFS (95% CI) from the time of first R/R MF was 1.3 (1.0–2.1) years. (4) Conclu-sion: High rates of R/R disease were observed after second- and third-line treatments in this re-al-world cohort, with longer median OS in patients receiving non-chemotherapy versus chemo-therapy. Following the standard management of MF and using recently approved targeted therapies can help improve patient outcomes in advanced-stage MF.

Only cross-sectional studies have demonstrated muscle deficits in children with spastic cerebral palsy (SCP). The impact of functional impairments on altered muscle growth remains unclear. This prospective longitudinal study modelled the morphological muscle growth in 87 children with SCP (age range 6 months to 11 years, Gross Motor Function Classification System [GMFCS] level I/II/III=47/22/18). Repeated ultrasound assessments were performed during 2-year (y) follow-up with an interval of minimal 6 months. Three-dimensional freehand ultrasound was applied to assess medial gastrocnemius muscle volume (MV), mid-belly cross-sectional area (CSA) and muscle belly length (ML). Non-linear mixed models compared trajectories of (normalized) muscle growth between GMFCS-I versus GMFCS-II&amp;III. MV and CSA growth trajectories showed piecewise model with 2 breakpoints, with the highest growth before 2y and negative growth rates after 6-9y. Before 2y, children with GMFCS-II&amp;III already showed lower growth rates compared to GMFCS-I. From 2-9y, the growth rates did not differ between GMFCS-levels. After 9y, a more pronounced reduction in normalized CSA was observed in GMFCS-II&amp;III. Different trajectories in ML growth were shown between the GMFCS-level subgroups. These longitudinal trajectories could be used to monitor the SCP muscle pathology during childhood and to optimize treatment planning and goals aiming to stimulate muscle growth

Background/Aims: Obstructive sleep apnea syndrome (OSAS) affects a large part of the aging population. It is characterized by chronic intermittent hypoxia and associated with neurocognitive dysfunction. One hypothesis is that the blood-brain barrier (BBB) functions could be altered by exosomes. Exosomes are nanovesicles found in biological fluids. Through the study of exosomes and their content in tau and amyloid beta (A), the aim of this study was to show how exosomes could be used as biomarkers of OSAS and of their cognitive disorders. Methods: Two groups of 15 volunteers from the PROOF cohort were selected: severe apnea (AHI >30) and control (AHI

Human disturbance, such as trampling, is an integral component of global change, yet we lack a comprehensive understanding of its effects on alpine ecosystems. Many alpine systems are seeing a rapid increase in recreation, and in understudied regions, such as the Coast Mountains of British Columbia, disturbance impacts on alpine plants remain unclear. We surveyed disturbed (trail-side) and undisturbed (off-trail) transects along elevational gradients of popular hiking trails in the T’aḵ’t’aḵ’múy̓in tl’a In̓inyáx̱a7n region (Garibaldi Provincial Park), Canada, focusing on dominant shrubs (Phyllodoce empetriformis, Cassiope mertensiana, Vaccinium ovalifolium) and graminoids (Carex spp). We used a hierarchical Bayesian framework to test for disturbance by elevation effects on total plant percent cover, maximum plant height and diameter (growth proxies), and buds, flowers, and fruits (reproduction proxies). We found that trampling reduces plant cover and impacts all species, but that effects vary by species and trait, and disturbance effects only vary with elevation for one species’ trait. Growth traits are more sensitive to trampling than reproductive traits, which may lead to differential impacts on population persistence and species level fitness outcomes. Our study highlights that disturbance responses are species-specific, and this knowledge can help land managers minimize disturbance impacts on sensitive vegetation types.

The association of the APOE4 (vs APOE3) isoform with an increased risk of Alzheimer’s Disease (AD) is unequivocal, but the underlying mechanisms remain incompletely elu-cidated. A prevailing hypothesis incriminates the impaired ability of APOE4 to clear neurotoxic amyloid-β peptides (Aβ) from the brain as the main mechanism linking apolipoprotein isoform to disease aetiology. APOE protein mediates lipid transport both within the brain and from the brain to the periphery, suggesting that lipids may be potential co-factors in APOE4-associated physiopathology. The present study reveals several alterations in pathways of lipid homeostasis in the brains of mice expressing the human APOE4 versus APOE3 isoform. Carriers of APOE4 had deficient cholesterol turnover, an imbalance in the ratio of specific classes of phospholipids, lower levels of phosphatidylethanolamines bearing poly-unsaturated fatty acids and an overall eleva-tion in levels of monounsaturated fatty acids. These modifications in lipid homeostasis were related with increased production of Aβ peptides as well as augmented levels of tau and phosphorylated tau in primary neuronal cultures. This suite of AP-OE4-associated anomalies in lipid homeostasis and neurotoxic protein levels may be related to the accrued risk for AD in APOE4 carriers and provides novel insights into potential strategies for therapeutic intervention.

Background: Skincare products are used daily to maintain a healthy skin (cleansing, moisturizing, protecting…), but their impact on this first layer, which corresponds to the skin microbiome, is still poorly understood. Preserving natural resources and mechanisms of the skin ecosystem is essential; an original approach based on these premises, called ecobiology, has recently emerged in skincare. Ecobiology considers the skin as an ever-evolving ecosystem which hosts human and microbial cells that interact together with their environment. In this context, we evaluated the impact on the skin microbiome of three types of leave-on face skincare products: a hydrophilic sterile solution, a micellar solution, and an oil-in-water emulsion. Materials and Methods: The individual microbial profiles of 20 Caucasian females were investigated. Samples were obtained twenty-four hours and four days following a daily application of the skincare products versus control area where no product was applied. To analyze the bacterial diversity and abundance of skin microbiome, a 16SrRNA gene sequencing was performed using the Illumina MiSeq platform. Results: Our results confirm the overall diversity of skin microbiome as previously observed and notably reveal the prevalence of Cutibacterium spp. and Staphylococcus spp. on sebaceous site (the back). Bacterial diversity and abundance were not affected by the products either twenty-four hours or four days after application, as indicated by comparison with the control. Moreover, no dissimilarity was observed between the three products versus their control, neither between each product. Conclusions: These preliminary results demonstrated for the first time that three different types of leave-on face skincare products such as a hydrophilic sterile solution, a micellar solution, and an emulsion have no impact on skin microbiome and can be considered as “microbiome friendly”.

Abstract: Oxidative metabolism is crucial for leukemic stem cell (LSC) function and drug resistance in acute myeloid leukemia (AML). Mitochondrial metabolism also affects the immune system and therefore the antitumor response. Modulation of oxidative phosphorylation (OxPHOS) has emerged as a promising approach to improve therapy outcome for AML patients. However, the effect of mitochondrial inhibitors on the immune compartment in the context of AML is yet to be explored. Immune checkpoints such as the ecto-nucleotidase CD39 and programmed dead ligand 1 (PD-L1) have been reported to be expressed in AML and linked to chemoresistance and poor prognosis. In the present study, we first demonstrated that a novel selective electron transfer chain complex (ETC) I inhibitor, EVT-701, decreased OxPHOS metabolism of murine and human cytarabine (AraC)-resistant leukemic cell lines. Furthermore, we showed that, while AraC induced immune response regulation by increasing CD39 expression and by reinforcing interferon-γ/PD-L1 axis, EVT-701 reduced CD39 and PD-L1 expression in vitro in a panel of both murine and human AML cell lines, especially upon AraC treatment. Altogether, this work uncovers a non-canonical function of ETCI in controlling CD39 and PD-L1 immune checkpoints, thereby improving the anti-tumor response in AML.

N-Nitroso-3-morpholinosydnonimine 3 was prepared by nitrosation of SIN-1 and characterized by 1H-NMR, 13C-NMR and HRMS. Its structure, confirmed by single crystal X-ray diffraction analysis, was found in agreement with its mesoionic and aromatic character. Unlike SIN-1, which releases both nitric oxide and superoxide radical, decomposition of this nitrosylated sydonimine could yield nitric oxide as the only decomposition product, and thus without the formation of toxic peroxynitrite.

This survey reports on the DNA identification and occurrence of Culex torrentium and Cx. pipiens s.s. in Belgium. These native disease vector mosquito species are morphologically difficult to separate and the biotypes of Cx. pipiens s.s. are morphologically indistinguishable. Culex torrentium and Cx. pipiens s.s. were identified using the COI and ACE2 loci. We recorded 1,248 Cx. pipiens s.s. and 401 Cx. torrentium specimens from 24 locations in Belgium (collected between 2017 and 2019). Culex pipiens biotypes pipiens and molestus, and their hybrids, were differentiated by fragment size analysis of the CQ11 locus (956 pipiens and 227 molestus biotype specimens, 29 hybrids). Hybrids were observed at 13 out of 16 sympatric sites. These results confirm that both species are widespread in Belgium, but while Cx. torrentium revealed many COI haplotypes, Cx. pipiens s.s. showed only one abundant haplotype. This latter observation may either reflect a recent population-wide demographic or range expansion, or a recent bottleneck, possibly linked to a Wolbachia infection. Finally, new evidence is provided for the asymmetric but limited introgression of the molestus biotype into the pipiens biotype.

This study develops an efficient, low-temperature process for formulating a nanoemulsion-based gel encapsulating Pituranthos tortuosus's essential oil, investigating its wound healing potential. The novel process ensured stable encapsulation of the medicinal plant's oil. The nanoemulsion was characterized using dynamic light scattering and transmission electron microscopy, followed by in vitro and in vivo tests to examine wound healing efficacy. Results revealed the gel's excellent stability, high encapsulation efficiency, and significant wound-healing effects. This research provides a new method for formulating Pituranthos tortuosus's essential oil nanoemulsion-based gel, emphasizing the potential role of plant-based therapies in healthcare advancement, and invites further exploration into the therapeutic applications of essential oil-encapsulating nanoemulsions.

Background: Little is known about potential confounding factors influencing the humoral response in individuals having received the BNT162b2 vaccine. Methods: Blood samples from 231 subjects were collected before and 14, 28 and 42 days following COVID-19 vaccination with BNT162b2. Anti-Spike Receptor-Binding-Domain protein (anti-Spike/RBD) immunoglobulin G (IgG) antibodies were measured at each time-point. Impact of age, sex, childbearing age status, hormonal therapy, blood group, body mass index and past-history of SARS-CoV-2 infection were assessed by multivariable analyses. Results and Conclusions: In naïve subjects, the level of anti-Spike/RBD antibodies gradually increased following administration of the first dose to reach the maximal response at day 28 and then plateauing at day 42. In vaccinated subjects with previous SARS-CoV-2 infection, the plateau was reached sooner (i.e. at day 14). In the naïve population, age had a significant negative impact on anti-Spike/RBD titers at day 14 and 28 while lower levels were observed for males at day 42, when corrected for other confounding factors. BMI as well as B and AB blood groups had a significant impact in various subgroups on the early response at day 14 but no longer after. No significant confounding factors were highlighted in the previously infected group.

Introduction: The objectives of this study were to (1) investigate the association between human blood type and COVID-19 infection in both inpatient and longitudinal populations at our institution in South Florida and (2) identify the association between blood type and severity of COVID-19 infection via presence of cellular biomarkers of severe infection in hospitalized individuals. Methods: This study consists of (1) a single-center retrospective analysis of 669 of 2,741 COVID-19 positive screened patients seen from January 1, 2020 until March 31, 2021 at the University of Miami Emergency Department (ED) who tested positive for COVID-19 infection and had a documented ABO blood type and (2) a longitudinal SARS-CoV-2 immunity study (“CITY”) at the University of Miami Miller School of Medicine consisting of 185 survey participants. COVID-19 outcome rates and 95% confidence intervals were calculated for each ABO blood type and Rh group using Chi-squared tests for categorical and ANOVA for continuous variables in the inpatient cohort and Chi-squared tests for the longitudinal cohort, all executed in R studio. Results: Our inpatient cohort had a mean age of 53.6 (± 17.9) years with 48% males and 52% females. When compared to patients with other blood types, those with O- demonstrated less risk of developing COVID-19 pneumonia (26.7% for O- vs. 69.2% for type A-, 56.5% for A+, 71.4% for AB+, 53.7% for B+, 51.5% for O+, p-value= 0.003 via Chi-squared test) and decreased mortality due to COVID-19 infection (17.0% mortality for O vs. 26.3% for A, 29.2% for B, p-value= 0.012 via Chi-squared test). Blood type O- demonstrated less elevated levels of LDH than did other blood types (p-value= 0.001, ANOVA) and a higher frequency of clinically accepted baseline levels of troponin (0.04 ng/mL) (p-value= 0.026, ANOVA) (Figure 1). Most of the longitudinal cohort was ABO blood grouping type O (47% (87/185)), with 33.5% type A, 14.1% B, and 5.4% AB. Most individuals were Rh positive (85.9%). There was no significant association found between COVID status (infection vs. non-infection) and ABO (Chi-squared test (3, N = 185) = 1.8, p = 0.6) or Rh (Chi-squared test (1, N = 185) = 0.16, p = 0.7) blood typing. Nearly all participants had been vaccinated (95.1% (176/185)), with a majority reporting primary vaccination with Pfizer (57.8% (107/185)), followed by Moderna (33% (61/185)), and Johnson & Johnson (4.3% (8/185)). 8 participants (4.3%) were unvaccinated. Conclusions: In an inpatient setting, blood type O sustained less risk of COVID-19 mortality and O- demonstrated less risk of developing COVID-19 pneumonia. In a longitudinal setting, there was no association found between blood type and COVID-19 severity. As the novelty of COVID-19 infection declines with time, further studies on risk-stratification by blood type are encouraged.

We studied the capacity of glutathione and a specific inactivated dry yeast rich in glutathione to protect white grape must from browning compared to using sulphur dioxide. The results indicate that sulphur dioxide drastically reduces the oxygen consumption rate, protects hydroxycinnamic acids from oxidation and prevents grape must against browning even in the presence of laccase. Glutathione, pure or in the form of a specific inactivated dry yeast rich in glutathione, also reduces the oxygen consumption rate but to a lesser extent than sulphur dioxide. It favours the formation of GRP from hydroxycinnamic acids and effectively protects grape must against browning in healthy grape conditions. Nevertheless, in the presence of laccase it was not effective enough. Therefore, both forms of glutathione can be considered as interesting alternative tools to sulphur dioxide for preventing browning in white grape must, but only when the grapes are healthy.

Over 130 countries have committed to reaching net-zero CO2 or GHG emissions by 2050, yet this ambition is rarely underpinned by robust policies. By applying a detailed integrated assessment modelling approach for Brazil, we assess, for the first time, the extent to which the existing and planned local policies could put Brazil on the path to its net zero pledge. This includes quantifying the role of nature-based solutions, such as protection and restoration, and engineered solutions, such as bioenergy with carbon capture and storage (BECCS). We show protection is the single most important climate mitigation measure at relatively low costs, whereas relying heavily on engineered solutions would jeopardise Brazil’s chances of achieving its net zero pledge. We also show that the mismatch between Brazil's short- and long-term climate targets reflects current weak environmental governance. Our analysis reinforces the urgent need for Brazil to eliminate illegal deforestation and go beyond to help fight climate change whilst curbing biodiversity loss.

Ecosystems are not merely vulnerable to climate change but, if sustainably restored and protected, are a major source of human resilience. Not only is the evidence-base for the importance of these “Nature-based Solutions” (NbS) growing rapidly, but NbS are featuring with increasing prominence in global climate change policy. Here we report on the prominence of NbS in the 141 adaptation components of the 167 Nationally Determined Contributions (NDCs) that were submitted to UNFCCC by all signatories of the Paris Agreement. In total, 103 nations include NbS in the adaptation component of their NDC, 76 nations include them in both their adaptation and mitigation component, and an additional 27 include them as part of their mitigation plans only. In other words, 130 nations—or 66% of all signatories to the Paris Agreement—have articulated intentions of working with ecosystems, in one form or another, to address the causes and consequences of climate change. However, commitments rarely translate into robust science-based targets. As climate pledges are revised in 2020, we urge the ecosystem science community to work closely with policymakers to identify meaningful adaptation targets that benefit both people and the ecosystems on which they depend.

Background: Patterns of humoral immune responses represent a major hurdle in terms of pig-to-human xenotransplantation approaches. The best-known xenogeneic glycan antigens pre-sent in pigs are the αGal (Galili-antigen) and the non-human sialic acid Neu5Gc. As there are further differences between porcine and human cellular surface glycosylation, a much broader range of glycan epitopes with xeno-reactive relevance can be anticipated. Therefore, we set-out to chemically modify porcine cellular surface glycans in a global approach by applying sodium peri-odate (NaIO4) oxidation. Methods: Porcine endothelial cells were exposed to oxidation with 1 to 5 mM NaIO4 for different time periods at 37°C or 4°C and under static or dynamic conditions. The impact on cellular sur-vival was determined applying live/dead-assays. Oxidation of αGal-epitopes was assessed by flu-orescence microscopy-based quantification of isolectin-B4 (IL-B4) staining. Overall immunogenic-ity of porcine cells was determined by human serum antibody binding. Results: Treatment of porcine endothelial cells and tissues with NaIO4 led to a reduced binding of the αGal-specific IL-B4 and/or human serum antibodies. NaIO4 revealed to be cytotoxic when performed at elevated temperature and for prolonged time. However, by applying 2 mM NaIO4 for 60 min at 4°C a high extent of cellular viability and a relevant reduction of detectable αGal epitope were observed. No differences were detected irrespectively on whether the cells were oxi-dized under static or flow conditions. Conclusion: Glycan epitopes on living cells can be oxidized with NaIO4 while maintaining their viability. Accordingly, this strategy holds promise to prevent immune reactions mediated by pre-formed anti-glycan antibodies.

The process of identifying and approving a new drug is a time-consuming and expensive procedure. One of the biggest issues to overcome is the risk of hepatotoxicity, which is one of the main reasons for drug withdrawal from the market. While animal models are the gold standard in preclinical drug testing, the translation of results into therapeutic intervention is often ambiguous due to interspecies differences in hepatic metabolism. The discovery of human induced Pluripotent Stem Cells (hiPSCs) and their derivatives has opened new possibilities for drug testing. We used mesenchymal stem cells and hepatocytes both derived from hiPSC, together with endothelial cells, to miniaturize the process of generating hepatic organoids. These organoids were then cultivated in vitro using both static and dynamic cultures. Additionally, we tested spheroids composed solely by induced hepatocytes. By miniaturizing the system, we demonstrated the possibility of maintaining the organoids, but not the spheroids, in culture for up to 15 days. This timeframe may be sufficient to carry out a hypothetical pharmacological test or screening. In conclusion, we propose that the hiPSC-derived liver organoids model could complement or, in the near future, replace the pharmacological and toxicological tests conducted on animals.

Chitin/chitosan and collagen are two of the most important bioactive compounds with applications in the pharmaceutical, veterinary, nutraceutical, cosmetic, biomaterials, and other industries. When extracted from fish and shellfish non-edible parts, by-catches, and invasive species, their use contributes to a more sustainable and circular economy. The present article reviews the scientific knowledge and publication trends along the marine chitin/chitosan and collagen value-chains and assesses how researchers, industry players, and end-users can bridge the gap between scientific understanding and industrial applications. Overall, research on chitin/chitosan remains focused on the compound itself rather than its market applications. Still, chitin/chitosan use is expected to increase in food and biomedical applications, while that of collagen is expected to increase in biomedical, cosmetic, pharmaceutical, and nutritional applications. Sustainable practices, such as the reuse of waste materials, contribute to strengthen both value-chains; the identified weaknesses include the lack of studies considering market trends, social sustainability, and profitability, as well as insufficient examination of intellectual property rights. Government regulations, market demand, consumer preferences, technological advancements, environmental challenges, and legal frameworks play significant roles in shaping both value-chains. Addressing these factors is crucial for seizing opportunities, fostering sustainability, complying with regulations, and maintaining competitiveness in these constantly evolving value-chains.

The NOD2 gene, involved in innate immune responses to bacterial peptidoglycan, has been found to be strongly associated with Crohn’s Disease, with an Odd Ratio ranging from 3 to 36. Families with 3 or more CD affected patients were related to high frequency of NOD2 gene variations as R702W, G908R, 1007fs and were reported in EPIMAD Registry. However, some rare CD multiplex families were described without identification of common NOD2 linked-to-disease variations. In order to identify new genetic variation(s) with a major effect on Crohn’s disease (CD), whole exome sequencing was performed in available subjects comprising 4 patients on 2 generations affected with Crohn’s disease without R702W and G908R variation, and 3 unaffected related subjects. A new rare and not yet reported missense variation of the NOD2 gene, the N1010K, was detected and co-segregated across affected patients. In silico evaluation and modeling highlighted evidences for a deleterious effect of the N1010K variation regarding CD. Moreover cumulative characterization of N1010K and 1007fs as compound heterozygous state in two more severely CD family members strongly suggesting that the N1010K should be a new risk factor involved in Crohn’s disease genetic susceptibility.

In this study dual PET and contrast enhanced MRI were combined to investigate their correlation per voxel in patients at initial diagnosis with suspected glioblastoma. Correlation with contrast enhancement (CE) as an indicator of BBB leakage was further used to evaluate whether PET signal is likely caused by BBB disruption alone, or rather attributable to specific binding after BBB passage. PET images with [18F]GE180 and the amino acid [18F]FET were acquired and normalized to healthy background (TBR). Contrast enhanced images were normalized voxel by voxel with the pre-contrast T1-weighted MRI to generate relative CE values (rCE). Voxel-wise analysis revealed a high PET signal even within the sub-volumes without detectable CE. No to moderate correlation of rCE with TBR voxel-values and a small overlap as well as a larger distance of the hotspots delineated in rCE and TBR-PET images were detected. In contrast, voxel-wise correlation between both PET modalities was strong for most patients and hotspots showed a moderate overlap and distance. The high PET signal in tumor sub-volumes without CE observed in voxel-wise analysis as well as the discordant hotspots emphasize the specificity of the PET signals and the relevance of combined differential information from dual PET and MRI images.

46 patients with a newly diagnosed, histologically verified glioma that was visually classified as [18F]FET-negative were included. Tumor volumes were defined using routine T2/FLAIR MRI data and applied to extract information from dynamic [18F]FET PET data, i.e. early and late tu-mor-to-background (TBR5-15, TBR20-40) images and time-to-peak (TTP) images. Radiomic features of healthy background were calculated from the tumor volume-of-interest mirrored to the con-tralateral hemisphere. Differences between tumor and healthy tissue features were compared us-ing Wilcoxon test. Additionally, the ability to distinguish tumor from healthy tissue was assessed using logistic regression. 5 % of features derived from TBR20-40 images were significantly differ-ent; 16 % of features derived from TBR5-15 images and 69 % of features derived from TTP images. The high number of significantly different features derived from TTP images was even found in isometabolic gliomas (after exclusion of photopenic gliomas) with visually normal [18F]FET up-take in static images. However, the differences did not reach satisfactory predictability for ma-chine learning based identification of tumor tissue. In conclusion, radiomic features derived from dynamic [18F]FET PET data may extract additional information even in [18F]FET-negative glio-mas, which should be investigated in larger cohorts and correlated with histological and out-come features in future studies.

Objectives: Monoclonal antibodies (mAbs) have proven to be a valuable tool against COVID-19, mostly among subjects with risk factors for progression to severe illness. Tixagevimab/cilgavimab (TIX/CIL), a combination of two Fc-modified human monoclonal antibodies, has been recently approved to be employed as early treatment. Methods: Two groups of immunocompromised patients exposed to different early treatments (i.e., TIX/CIL vs. other mAbs [casirivimab/imdevimab, bamlanivimab/etesevimab, sotrovimab]) were compared in terms of clinical outcomes (hospitalization and mortality within 14 days from administration) and time to the negativity of nasal swabs. We used either Pearson’s chi-square or Fisher’s exact test for categorical variables, whereas the Wilcoxon rank–sum test was employed for continuous ones. Kaplan–Meier curves were produced to compare the time to nasopharyngeal swab negativity. Results: Early treatment with TIX/CIL was administered to 19 immunocompromised patients, while 89 patients received other mAbs. Most of them were solid organ transplant recipients or suffering from hematologic or solid malignancies. Overall, no significant difference was observed between the two groups in terms of clinical outcomes. In the TIX/CIL group, one patient (1/19, 5.3%), who was admitted to the emergency room within the first 14 days from treatment and was hospitalised due to COVID-19 progression, died. Regarding the time to nasal swab negativity, no significant difference (p=0.088) emerged. Conclusions: Early treatment of SARS-CoV-2 infection with TIX/CIL shows favourable outcomes in a small group of immunocompromised patients, reporting no significant difference when compared to similar patients treated with other mAbs.

BK polyomavirus (BKPyV) is still a real threat in the management of kidney transplantation. Immunosuppressive treatment disrupts the equilibrium between virus replication and immune response, and uncontrolled BKPyV replication leads to nephropathy (BKPyV nephropathy). The first evidence of BKPyV reactivation in transplant recipients is the detection of viral shedding in urine, which appears in 20% to 60% of patients, followed by BKPyV viremia in 10-20% of kidney transplant recipients. BKPyV nephropathy eventually occurs in 1-10% of this population, mainly within the first 2 years post-transplantation, causing graft loss in about half of those patients. Few data exist regarding the pediatric population and we focus on them. In this paper, we review the existing diagnostic methods, we summarize the evidences on the role of BKPyV humoral and cellular immunity in the modulation of the clinical course of BKPyV infection and as potential predictors of the outcome. We look at the known risk factors of BKPyV nephropathy in the immunosuppressed patient. Finally, we propose a sensible clinical attitude in order to screen and manage BKPyV infection in kidney transplant children.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.