It has been several years since highly purified cannabidiol (CBD) was registered as a medication that can be used in children of at least 2 years of age to treat different types of seizures related to Lennox–Gastaut syndrome (LGS), Dravet syndrome (DS), and more recently tuberous sclerosis complex (TSC). During this time, 39 randomized clinical trials (RCTs) and 13 meta-analyses on the efficacy and safety of CBD treatment have been published. Each of the meta-analyses had its own criteria for the RCTs' inclusion and, therefore, slightly different interpretations of the analyzed data. Each of them contributed in its own way to the understanding of CBD pharmacology, mechanisms of therapeutic action, development of adverse reactions, and drug–drug interactions. Hence, it seemed reasonable to gather the most relevant data in one article and present all the current knowledge on the use of CBD in epilepsy. The results of the 13 meta-analyses presented herein confirmed the effectiveness and safety of CBD in children and adolescents with DREs. In adults, reliable conclusions cannot be drawn due to insufficient data. Full article

We study epidemic spreading in complex networks by a multiple random walker approach. Each walker performs an independent simple Markovian random walk on a complex undirected (ergodic) random graph where we focus on the Barabási–Albert (BA), Erdös–Rényi (ER), and Watts–Strogatz (WS) types. Both walkers and nodes can be either susceptible (S) or infected and infectious (I), representing their state of health. Susceptible nodes may be infected by visits of infected walkers, and susceptible walkers may be infected by visiting infected nodes. No direct transmission of the disease among walkers (or among nodes) is possible. This model mimics a large class of diseases such as Dengue and Malaria with the transmission of the disease via vectors (mosquitoes). Infected walkers may die during the time span of their infection, introducing an additional compartment D of dead walkers. Contrary to the walkers, there is no mortality of infected nodes. Infected nodes always recover from their infection after a random finite time span. This assumption is based on the observation that infectious vectors (mosquitoes) are not ill and do not die from the infection. The infectious time spans of nodes and walkers, and the survival times of infected walkers, are represented by independent random variables. We derive stochastic evolution equations for the mean-field compartmental populations with the mortality of walkers and delayed transitions among the compartments. From linear stability analysis, we derive the basic reproduction numbers $R_M,R_0$ with and without mortality, respectively, and prove that $R_M<R_0$. For $R_M,R_0>1$, the healthy state is unstable, whereas for zero mortality, a stable endemic equilibrium exists (independent of the initial conditions), which we obtained explicitly. We observed that the solutions of the random walk simulations in the considered networks agree well with the mean-field solutions for strongly connected graph topologies, whereas less well for weakly connected structures and for diseases with high mortality. Our model has applications beyond epidemic dynamics, for instance in the kinetics of chemical reactions, the propagation of contaminants, wood fires, and others. Full article

The carbon isotopic composition of dissolved organic carbon (δ¹³C_DOC) in speleothems, based on high-precision U-Th ages, has great potential to reconstruct past ecology, microbial activity, and carbon cycling. Identifying the reliability of the pretreatment and measurement of speleothem δ¹³C_DOC is therefore essential to putting it into practice. Actually, we have previously verified the reliability of the method for speleothem δ¹³C_DOC measurements. However, it was only based on the final δ¹³C_DOC values of homogeneous speleothem powder and is unable to evaluate the effects of different experimental conditions and the impacts of adding acid on δ¹³C_DOC if using speleothem as the study samples. In this study, we used an organic reagent (potassium sorbate) as the study sample and designed a conditional experiment that simulates the protocols for speleothem δ¹³C_DOC analysis and presented the resulting data to inspect the effects of the experimental processes on the analysis of δ¹³C_DOC. The results show that the standard deviation of duplicate samples is 0.1‰, which is close to that of the previous work for organic reagents and water samples, and the results were not affected by different experimental conditions and operation steps (such as adding orthophosphoric acid, digestion time, and storage duration of resulting CO₂ in storage vessels), suggesting that this method is robust to detect the speleothem δ¹³C_DOC. Considering the range and standard deviation of results, we proposed that the δ¹³C_DOC record could be used in various studies when the amplitudes of the δ¹³C_DOC record are larger than 0.1‰, especially greater than 0.4‰. Full article

Similarity measures on trapezoidal-valued intuitionistic fuzzy numbers (TrVIFNs) are functions that measure the closeness between two TrVIFNs, which has a lot of applications in the area of pattern recognition, clustering, decision-making, etc. Researchers around the world are proposing various similarity measures on the generalizations of fuzzy sets. However, many such measures do not satisfy the condition that “the similarity between two fuzzy numbers is equal to 1 implies that both the fuzzy numbers are equal” and this gives a pathway for the researchers to introduce different similarity measures on various classes of fuzzy sets. Also, all of them try to find out the similarity by using a single function, and in the present study, we try to propose a combined similarity measure principle by using four functions (four similarity measures). Thus, the main aim of this work is to introduce a few sets of similarity measures on the class of TrVIFNs and propose a combined similarity measure principle on TrVIFNs based on the proposed similarity measures. To do this, in this paper, firstly, we propose four distance-based similarity measures on TrVIFNs using score functions on TrVIFNs and study their mathematical properties by establishing various propositions, theorems, and illustrations, which is achieved by using numerical examples. Secondly, we propose the idea of a combined similarity measure principle by using the four proposed similarity measures sequentially, which is a first in the literature. Thirdly, we compare our combined similarity measure principle with a few important similarity measures introduced on various classes of fuzzy numbers, which shows the need for and efficacy of the proposed similarity measures over the existing methods. Fourthly, we discuss the trapezoidal-valued intuitionistic fuzzy TOPSIS (TrVIF-TOPSIS) method, which uses the proposed combined similarity measure principle for solving a multi-criteria decision-making (MCDM) problem. Then, we discuss the applicability of the proposed modified TrVIF-TOPSIS method by solving a model problem. Finally, we discuss the sensitivity analysis of the proposed approaches by using various cases. Full article

The pursuit of Artificial Intelligence (AI) that emulates human cognitive processes is a cornerstone of ethical AI development, ensuring that emerging technologies can seamlessly integrate into societal frameworks requiring nuanced understanding and decision-making. Zero-Shot Instance Retrieval (ZSIR) stands at the forefront of this endeavour, potentially providing a robust platform for AI systems, particularly large visual language models, to demonstrate and refine cognition-aligned learning without the need for direct experience. In this paper, we critically evaluate current cognition alignment methodologies within traditional zero-shot learning paradigms using visual attributes and word embedding generated by large AI models. We propose a unified similarity function that quantifies the cognitive alignment level, bridging the gap between AI processes and human-like understanding. Through extensive experimentation, our findings illustrate that this similarity function can effectively mirror the visual–semantic gap, steering the model towards enhanced performance in Zero-Shot Instance Retrieval. Our models achieve state-of-the-art performance on both the SUN (92.8% and 82.2%) and CUB datasets (59.92% and 48.82%) for bi-directional image-attribute retrieval accuracy. This work not only benchmarks the cognition alignment of AI but also sets a new precedent for the development of visual language models attuned to the complexities of human cognition. Full article

Neural networks (NNs) have shown outstanding performance in solar photovoltaic (PV) power forecasting due to their ability to effectively learn unstable environmental variables and their complex interactions. However, NNs are limited in their practical industrial application in the energy sector because the optimization of the model structure or hyperparameters is a complex and time-consuming task. This paper proposes a two-stage NN optimization method for robust solar PV power forecasting. First, the solar PV power dataset is divided into training and test sets. In the training set, several NN models with different numbers of hidden layers are constructed, and Optuna is applied to select the optimal hyperparameter values for each model. Next, the optimized NN models for each layer are used to generate estimation and prediction values with fivefold cross-validation on the training and test sets, respectively. Finally, a random forest is used to learn the estimation values, and the prediction values from the test set are used as input to predict the final solar PV power. As a result of experiments in the Incheon area, the proposed method is not only easy to model but also outperforms several forecasting models. As a case in point, with the New-Incheon Sonae dataset—one of three from various Incheon locations—the proposed method achieved an average mean absolute error (MAE) of 149.53 kW and root mean squared error (RMSE) of 202.00 kW. These figures significantly outperform the benchmarks of attention mechanism-based deep learning models, with average scores of 169.87 kW for MAE and 232.55 kW for RMSE, signaling an advance that is expected to make a significant contribution to South Korea's energy industry. Full article

Background: The main objective of this study was the development of a specific load platform that would meet the needs of gymnasts and acrobatic coaches. This new platform has larger dimensions and is an identical structure to the plywood floor surface normally used; it was designed to make competitions with gymnasts safer and more like a real training situation. During a landing, there is high body stiffness, especially in the knees and ankles, which can cause injuries due to the number of repetitions performed in this gymnastics specialty. Methods: A group of 10 volunteers, with a mean age of 14.7 ± 2.4 years, performed at least 10 valid vertical jumps on each platform. Results: Despite being a preliminary study, this specific platform was shown to be more suitable for gymnastic use, compared to the industrial one, which represents a significant advantage for the modality. In fact, this platform is similar to the surface used for training and competition, allowing athletes to perform the jump in a similar way, and for the results to be replicable during the practice of the sport. The standard deviation values were lower, which shows that the new platform was more suitable for acrobatic gymnastics. Conclusions: As the maximum vertical load induced during landing after a jump has a significant effect on the likelihood of gymnasts suffering injuries, the development of a new load platform specifically for acrobatic gymnastics is clearly an improvement in this discipline. Knowledge of the load transmitted to the body can help coaches and athletes in defining training, and avoiding the possible occurrence of injuries. Therefore, it is necessary to use a platform that can accurately evaluate the load transmitted to the acrobatic gymnasts during real training and competition conditions, which is achieved with this new platform. Full article

Green infrastructure (GI) networks comprising multiple natural and artificial habitats are important tools for the management of ecosystem services. However, even though ecosystem services are deeply linked with the state of biodiversity, many approaches to GI network planning do not explicitly consider the ecological needs of biotic communities, which are often threatened by anthropic activities even in presence of protected areas. Here, to contribute in fill this gap, we describe an easy-to-apply, biodiversity-centric approach to model an ecological network as a backbone for a GI network, based on the ecological needs of a range of representative species. For each species, ideal habitats (nodes) were identified, and crossing costs were assigned to other habitat types depending on their compatibility with the species ecology. Corridors linking the nodes were then mapped, minimizing overall habitat crossing costs. We applied the method to the Isonzo–Vipacco river area in Northern Italy, highlighting a potential ecological network where nodes and corridors occupied 27% and 11.8% of the study area, respectively. The prospective of its conflicts with anthropic activities and possible solutions for its implementation was also discussed. Our method could be applied to a variety of situations and geographic contexts, being equally useful for supporting the protection of entire biocenoses or of specific sensitive species, as well as enhancing the ecosystem services they provide. Full article

An 8-week feeding trial was performed to investigate the effects of dietary bile acids on growth, glucose metabolism, and intestinal health in spotted seabass (Lateolabrax maculatus) reared at high temperatures (33 °C). The fish (20.09 ± 1.12 g) were fed diets supplemented with bile acids: 0 (Con), 400 (BA400), 800 (BA800), and 1200 (BA1200) mg/kg, respectively. The results showed that the growth was promoted in fish at the BA800 treatment compared with the control (p < 0.05). Increased enzyme activities and transcripts of gluconeogenesis in the liver were observed, whereas decreased enzyme activities and transcripts of glycolysis, as well as glycogen content, were shown in the BA800 treatment (p < 0.05). The transcripts of bile acid receptors fxr in the liver were up-regulated in the BA800 treatment (p < 0.05). A bile acid supplementation of 800 mg/kg improved the morphological structure in the intestine. Meanwhile, intestinal antioxidant physiology and activities of lipase and trypsin were enhanced in the BA800 treatment. The transcripts of genes and immunofluorescence intensity related to pro-inflammation cytokines (il-1β, il-8, and tnf-α) were inhibited, while those of genes related to anti-inflammation (il-10 and tgf-β) were induced in the BA800 treatment. Furthermore, transcripts of genes related to the NF-κB pathway in the intestine (nfκb, ikkα, ikkꞵ, and ikbα1) were down-regulated in the BA800 treatment. This study demonstrates that a dietary bile acid supplementation of 800 mg/kg could promote growth, improve glucose metabolism in the liver, and enhance intestinal health by increasing digestive enzyme activity and antioxidant capacity and inhibiting inflammatory response in L. maculatus. Full article

Thermal deformation behavior of Cu–Cr–Sn alloy ingots under deformation temperatures ranging from 600 °C to 950 °C and strain rates from 0.01 s⁻¹ to 10 s⁻¹ was investigated in detail. The thermal deformation constitutive equation and thermal processing map of the alloy were established, respectively. The activation energy Q was determined as 430.61 KJ/mol. The optimal deformation system corresponding to the hot working diagram was a deformation temperature of 900 °C and strain rate of 0.1 s⁻¹. Under these deformation conditions, twin dynamic recrystallization (TDRX), continuous dynamic recrystallization (CDRX), and discontinuous dynamic recrystallization (DDRX) occurred simultaneously, with the twinning process causing the stress–strain curve to exhibit a wavy change. The thermal deformation microstructure of the alloy is co-regulated by different recrystallization mechanisms, with DDRX occurring mainly at low deformation temperatures, and both CDRX and DDRX occurring at high deformation temperatures. Full article

Background: Early post-operative airway management after laryngo-tracheal surgery is crucial. Acute respiratory failure due to glottis’ edema may occur, requiring reintubation. This can prolong ventilatory assistance, jeopardizing anastomosis. To date, only judicious steroid administration and fluid management are available to avoid more invasive procedures. High-flow oxygen therapy (HFOT) is a noninvasive O₂ support method providing humidification, warmed air, and Positive End-Expiratory Pressure (AIRVO2). No data about HFOT use to prevent early complications after laryngo-tracheal surgery are reported in the literature. Methods: Between September 2020 and September 2022, 107 consecutive patients who underwent laryngo-tracheal surgery received HFOT (Group A). Data and long-term results were compared with those of 80 patients operated between September 2018 and August 2020 (Group B), when HFOT was not available. All patients were operated in a single center. No pre- or post-operative settings changed, except for HFOT introduction. We analyzed and compared the risk for “delayed” reintubation (unexpected reintubation within the first 24–48 h after extubating/laryngeal mask removal) in the two groups. Results: No patients reported HFOT-related adverse events. The control group (B) presented “delayed” reintubation in 37% (p = 0.027), intensive care unit admission in 67% (p = 0.005) and longer hospital stay (p = 0.001) compared to the HFOT group (A). The minor complications’ rate was 3% in both group and overall mortality was 0%. Re-stenosis was described in 4.6% of the HFOT group, without a statistically significant difference (p = 0.7006). Conclusions: Our study is the first to investigate HFOT use in patients undergoing laryngo-tracheal surgery, potentially representing a consistent innovation in the peri-operative management of these patients. With the limitation of a retrospective series, we would suggest HFOT use for preventing post-operative reintubation rate, possibly reducing ICU admissions and hospital stays. Full article

The increase in emissions and concentration of carbon dioxide in the atmosphere necessitates the implementation of direct carbon dioxide capture technologies. The article presents the characteristics of a single-stage membrane unit for the direct capture of carbon dioxide from the air. A membrane with a selectivity of ${\mathsf{\alpha }}_{{\mathrm{C}\mathrm{O}}_2/{\mathrm{N}}_2}=70$ and permeability ${\mathrm{P}}_{{\mathrm{C}\mathrm{O}}_2}=108\frac{{\mathrm{m}}^3\left(\mathrm{S}\mathrm{T}\mathrm{P}\right)}{{(\mathrm{m}}^2·\mathrm{h}·\mathrm{b}\mathrm{a}\mathrm{r})}$ is chosen as the reference variant. It is demonstrated that increasing the pressure difference in the system by reducing the pressure of the permeate stream results in an improvement of all analyzed parameters. Manipulating both the membrane surface and its CO₂ permeability yields similar results. With an increase in permeability or membrane surface area, the proportion of CO₂ in the retentate and permeate decreases, while the degree of carbon dioxide recovery increases. However, the energy intensity of the process is a complex issue due to the presence of a local minimum in the obtained characteristics. Therefore, a relationship between the constants of energy intensity values for the separation process on the surface area field and CO₂ membrane permeability is presented. The minimum energy intensity of the process obtained is 22.5 $\mathrm{k}\mathrm{W}\mathrm{h}/{\mathrm{k}\mathrm{g}}_{{\mathrm{C}\mathrm{O}}_2}$. The CO₂ content in the retentate for all analyses did not exceed 280 ppm. Full article

Coal mining often produces severe environmental effects, including impacts on the soil system and, specifically, on hydropedological conditions that control the leaching of significant ions and Potentially Toxic Elements (PTEs). The research objective is to assess changes in the hydropedological conditions in an area with a coal mining waste pile that underwent self-burning. An integrative approach was implemented, starting with the definition of hydropedological zoning based on field observations of soil formation factors (namely, parent material, relief, biological activity, anthropic influence, and time). The soil profile in each hydropedological zone was characterized regarding morphological features. The upper mineral horizons were sampled and characterized in terms of mineralogy and PTE geochemistry. Field measurements of unsaturated hydraulic conductivity, soil water content, and hydrophobicity were performed. Afterwards, the hydrogeochemistry of leachates was determined, and the soil leaching potential was evaluated. The research outcomes express substantial differences regarding the hydropedological zones: development of different soil profiles, diverse mineralogy and PTE geochemistry, higher unsaturated hydraulic conductivity and leaching of major ions, and PTEs in soils affected by coal mining activities. Finally, a Principal Component Analysis confirmed the existence of significant contrasts according to hydropedological zoning. Full article

The present study examines the effects of China’s comprehensive big data pilot zone policy on urban ecological resilience. This is achieved through the utilization of a quasi-natural experiment, employing panel data from 217 prefecture-level cities in China spanning the years 2010 to 2021. The research revealed that China’s extensive policy on big data pilot zones has a notable and favorable influence on the ecological resilience of urban areas. This impact is both constant and subject to variation across different regions. The aforementioned impact is attained by means of progressions in industrial structure and the introduction of innovative green technologies. Furthermore, the strategy exerts a beneficial impact on the ecological resilience of urban areas in adjacent regions by means of spatial spillover effects. Full article

As the number of electronic gadgets in our daily lives is increasing and most of them require some kind of human interaction, this demands innovative, convenient input methods. There are limitations to state-of-the-art (SotA) ultrasound-based hand gesture recognition (HGR) systems in terms of robustness and accuracy. This research presents a novel machine learning (ML)-based end-to-end solution for hand gesture recognition with low-cost micro-electromechanical (MEMS) system ultrasonic transducers. In contrast to prior methods, our ML model processes the raw echo samples directly instead of using pre-processed data. Consequently, the processing flow presented in this work leaves it to the ML model to extract the important information from the echo data. The success of this approach is demonstrated as follows. Four MEMS ultrasonic transducers are placed in three different geometrical arrangements. For each arrangement, different types of ML models are optimized and benchmarked on datasets acquired with the presented custom hardware (HW): convolutional neural networks (CNNs), gated recurrent units (GRUs), long short-term memory (LSTM), vision transformer (ViT), and cross-attention multi-scale vision transformer (CrossViT). The three last-mentioned ML models reached more than 88% accuracy. The most important innovation described in this research paper is that we were able to demonstrate that little pre-processing is necessary to obtain high accuracy in ultrasonic HGR for several arrangements of cost-effective and low-power MEMS ultrasonic transducer arrays. Even the computationally intensive Fourier transform can be omitted. The presented approach is further compared to HGR systems using other sensor types such as vision, WiFi, radar, and state-of-the-art ultrasound-based HGR systems. Direct processing of the sensor signals by a compact model makes ultrasonic hand gesture recognition a true low-cost and power-efficient input method. Full article

Synanthropic flora (weeds, i.e., spontaneously developed plants) are plants that accompany humans, appearing as a result of anthropopressure as well as after its cessation. The potential of synanthropic flora in shaping green areas usually brings many measurable benefits that depend on land management in cities. This study aimed to determine the preferences and attitudes of adults towards synanthropic flora in settlement units. This article presents survey results from 447 city residents. The obtained results were statistically analyzed using the k-means clustering method to identify segments of respondents with similar attitudes and preferences toward synanthropic flora. Mann–Whitney U tests were employed to determine statistical differences in the demographic variables among the analyzed clusters of respondents. Additionally, multiple regression analysis was performed to identify the opinions and attitudes towards synanthropic flora that may influence their greater acceptance in the vicinity of residential areas. The results obtained in the multiple regression analysis indicate that the respondent’s evaluation of the level of support for the introduction of more synanthropic vegetation into urban greenery (Yw) grows with the increase in the acceptance of synanthropic plants’ occurrence in the surroundings. Residents’ acceptance of synanthropic flora in green areas is at a relatively high level. Full article

This article presents the verification of the hypothesis on using certain approximation curves in the evaluation of used lubricating oil. These curves are plotted for fresh lubricating oil to approximate the parameters of lubricating oil diluted with diesel oil. To confirm the hypothesis, an experiment is conducted to determine the flash point, initial boiling point, density at 15 °C, kinematic viscosity at 40 °C and 100 °C, and viscosity index. The analysis covers fresh oil and used SAE 30 grade Marinol CB-30 RG1230 oil taken from the circulating lubrication system of a supercharged, trunk-piston, 4-stroke ZUT Zgoda Sulzer 5 BAH 22 engine that is located in the Marine Power Plant Laboratory of the Maritime University of Szczecin. Undiluted lubricating oils (both fresh and used) and mixtures of lubricating oils with diesel oil are examined for diesel oil concentrations in the mixture equal to 1, 2, 5, 10, 15, and 20% m/m. Orlen Efecta Diesel Biodiesel is used to prepare the mixtures. The functions approximating the parameters for fresh oil are determined and adapted to describe the variation of the same parameters for the used lubricating oil. For each case, the coefficient of determination, the maximum relative error of the model fitting to the experimental results, and the root mean square error (RMSE) are determined. In the experiment, the variation in the parameters of the used lubricating oil remained the same as for fresh oil parameters. Thus, the research hypothesis is confirmed. Full article

Antifreeze peptides have become effective antifreeze agents for frozen products, but their low quantity of active ingredients and high cost limit large-scale application. This study used the glycosylation of fish collagen peptides with glucosamine hydrochloride catalyzed by transglutaminase to obtain a transglutaminase-catalyzed glycosylation product (TGP) and investigate its antifreeze effect on tilapia. Compared with the blank group, the freshness (pH value of 6.31, TVB-N value of 21.7 mg/100 g, whiteness of 46.28), textural properties (especially hardness and elasticity), and rheological properties of the TGP groups were significantly improved. In addition, the protein structures of the samples were investigated using UV absorption and fluorescence spectroscopy. The results showed that the tertiary structure of the TGP groups changed to form a dense polymer. Therefore, this approach can reduce the denaturation and decomposition of muscle fibers and proteins in fish meat more effectively and has a better protective effect on muscle structure and protein aggregation, improving the stability of fish meat. This study reveals an innovative method for generating antifreeze peptides by enzymatic glycosylation, and glycosylated fish collagen peptide products can be used as new and effective green antifreeze agents in frozen foods. Full article

Micro-ROS is widely used to bridge the performance gap between resource-constrained microcontrollers and powerful computing devices in ROS-based robotic applications. After modeling the callback scheduling module and the communication module in micro-ROS, we found that there are some design flaws that significantly impact the real-time performance of micro-ROS. To improve the timing predictability and run-time efficiency of micro-ROS, we design and implement a priority-driven chain-aware scheduling system (PoDS) based on the existing micro-ROS architecture. The experimental results demonstrate that our proposed PoDS exhibits significantly improved real-time performance compared to the default micro-ROS. Full article

A novel rare mutation in the pore region of Nav1.5 channels (p.L889V) has been found in three unrelated Spanish families that produces quite diverse phenotypic manifestations (Brugada syndrome, conduction disease, dilated cardiomyopathy, sinus node dysfunction, etc.) with variable penetrance among families. We clinically characterized the carriers and recorded the Na⁺ current (I_Na) generated by p.L889V and native (WT) Nav1.5 channels, alone or in combination, to obtain further insight into the genotypic–phenotypic relationships in patients carrying SCN5A mutations and in the molecular determinants of the Nav1.5 channel function. The variant produced a strong dominant negative effect (DNE) since the peak I_Na generated by p.L889V channels expressed in Chinese hamster ovary cells, either alone (−69.4 ± 9.0 pA/pF) or in combination with WT (−62.2 ± 14.6 pA/pF), was significantly (n ≥ 17, p < 0.05) reduced compared to that generated by WT channels alone (−199.1 ± 44.1 pA/pF). The mutation shifted the voltage dependence of channel activation and inactivation to depolarized potentials, did not modify the density of the late component of I_Na, slightly decreased the peak window current, accelerated the recovery from fast and slow inactivation, and slowed the induction kinetics of slow inactivation, decreasing the fraction of channels entering this inactivated state. The membrane expression of p.L889V channels was low, and in silico molecular experiments demonstrated profound alterations in the disposition of the pore region of the mutated channels. Despite the mutation producing a marked DNE and reduction in the I_Na and being located in a critical domain of the channel, its penetrance and expressivity are quite variable among the carriers. Our results reinforce the argument that the incomplete penetrance and phenotypic variability of SCN5A loss-of-function mutations are the result of a combination of multiple factors, making it difficult to predict their expressivity in the carriers despite the combination of clinical, genetic, and functional studies. Full article

Ceramic sherds from approximately 20 samples of lead-glazed tableware, recovered from diverse archaeological sites, including three repurposed storage pits transformed into dumpsters within the medieval city of Santarém (13th–14th century), underwent a meticulous examination. This investigation utilised techniques such as micro-Raman, ground-state diffuse reflectance absorption, and X-ray fluorescence spectroscopies, in addition to X-ray diffraction and stereomicroscopy. A parallel study was conducted on contemporaneous European ceramics (glazed sherds) sourced from archaeological sites dating back to the 13th–15th centuries in Saintonge (France), Ardenne, Zomergem, and Bruges (Belgium), as well as Surrey–Hampshire, Kingston, and Cheam (England). The first premise for comparing the Santarem samples with European production locations was their frequent commercial relations with Portugal and the frequency of these productions being found in Portugal. The colour of the ceramic bodies is predominantly white or whitish, with a few exhibiting a vivid red hue. Analyses of the fabric, mineralogical, and elemental composition of the sherds suggest that the majority of Santarém’s glazed ceramics were locally or regionally produced, potentially derived from a Pliocene kaolin-rich sand formation. However, this conclusion is not supported by the absence of discovered lead glaze kilns or workshops in Santarém for the late Middle Ages. Full article

Esophageal squamous cell carcinoma (ESCC) is a deadly consequence of radiation exposure to the esophagus. ESCC arises from esophageal epithelial cells that undergo malignant transformation and features a perturbed squamous cell differentiation program. Understanding the dose- and radiation quality-dependence of the esophageal epithelium response to radiation may provide insights into the ability of radiation to promote ESCC. We have explored factors that may play a role in esophageal epithelial radiosensitivity and their potential relationship to ESCC risk. We have utilized a murine three-dimensional (3D) organoid model that recapitulates the morphology and functions of the stratified squamous epithelium of the esophagus to study persistent dose- and radiation quality-dependent changes. Interestingly, although high-linear energy transfer (LET) Fe ion exposure induced a more intense and persistent alteration of squamous differentiation and 53BP1 DNA damage foci levels as compared to Cs, the MAPK/SAPK stress pathway signaling showed similar altered levels for most phospho-proteins with both radiation qualities. In addition, the lower dose of high-LET exposure also revealed nearly the same degree of morphological changes, even though only ~36% of the cells were predicted to be hit at the lower 0.1 Gy dose, suggesting that a bystander effect may be induced. Although p38 and ERK/MAPK revealed the highest levels following high-LET exposure, the findings reveal that even a low dose (0.1 Gy) of both radiation qualities can elicit a persistent stress signaling response that may critically impact the differentiation gradient of the esophageal epithelium, providing novel insights into the pathogenesis of radiation-induced esophageal injury and early stage esophageal carcinogenesis. Full article