The treatment adherence of narcotics-addicted individuals with reduced incidences of relapse can be enhanced by a sustained drug release formulation of antinarcotics. So far, different drug formulations have been reported with sustained drug release periods of 28 and 35 days. To further enhance this duration, different formulations of injectable hydrogels (IHs) have been developed by combining low molecular weight (LMW) and high molecular weight (HMW) chitosan (CS) with guar gum (GG) and crosslinking them by sodium bi phosphate dibasic. The structural, morphological, and physicochemical properties of LMW-CS IH, and HMW-CS IH were evaluated using Fourier transform infrared spectroscopy (FT-IR), thermo-gravimetric analysis (TGA), scanning electron microscopy (SEM), and rheological, swelling, and biodegradation analysis. The HMW-CS IH showed high crosslinking, increased thermal stability, high mechanical strength, elevated swelling, and low biodegradation. The antinarcotic drugs naltrexone (NTX) and disulfiram (DSF) were loaded separately into the HMW-CS IH and LMW-CS IH. The release of NTX and DSF was investigated in phosphate buffer saline (PBS) and ethanol (0.3%, 0.4%, and 0.5%) over a 56-day period using an UV spectrophotometer. The drug release data were tested in zero-order, first-order, and Korsemeyer–Peppas mathematical models. In PBS, all prepared formulations followed non-Fickian drug release, while in ethanol, only NTX HMW-CS IH followed non-Fickian release in all three different concentrations of ethanol. Full article

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome (GS), is a genetic disorder characterized by the development of multiple cutaneous BCCs due to mutations in the hedgehog signaling pathway. The use of hedgehog pathway inhibitors—vismodegib and sonidegib—has emerged as a promising therapeutic strategy for managing BCCs in individuals with GS. In a retrospective study conducted between March 2012 and January 2024, a cohort of 16 Gorlin syndrome patients who received treatment with either sonidegib or vismodegib were analyzed. The primary objectives of the study were to evaluate the efficacy, safety profile, and duration of response to oral hedgehog inhibitors in this patient population. The study assessed various parameters, including the number of new BCCs that developed before and after treatment initiation, the duration and sustainability of treatment responses, as well as the incidence of adverse effects associated with hedgehog inhibitor therapy. The findings of the study revealed that sustained treatment with hedgehog inhibitors could effectively suppress the progression of both new and existing BCCs. Furthermore, the results indicated that sonidegib exhibited superior efficacy and safety compared to vismodegib in the treatment of BCCs in individuals with GS. Notably, adjustments to the administration schedule of sonidegib were found to improve tolerability without compromising therapeutic efficacy, potentially leading to prolonged durations of treatment response and disease control. Full article

Oral disease interventions primarily focus on behavioral changes like dietary improvements and ensuring better oral hygiene. However, recognizing the influence of biological factors, including genetics and early-life nutrition, is crucial. Iron deficiency (ID) and its advanced form, iron deficiency anemia (IDA), affect nearly two billion people globally, especially children and pregnant women. We conducted a comprehensive search using Medline via EndNote and Web of Science, employing keywords related to iron deficiency anemia (IDA), and we identified 36 studies deemed relevant for inclusion in this literature review. IDA prevalence is notably high among pregnant women and young children. Both IDA and early-childhood caries (ECC) disproportionately affect impoverished populations, highlighting the socioeconomic dimension of this issue. IDA presents with various oral mucosal changes and is closely linked to candidiasis. Additionally, IDA can hinder tooth development and weaken the immune response. Multiple population surveys have revealed a significant association between ECC and IDA. While some studies have explored the IDA–periodontal disease link, the current evidence is relatively limited in its robustness. In conclusion, more comprehensive longitudinal studies are essential to deepen our understanding of the IDA–oral disease connection. Investigating the underlying biological mechanisms is critical to developing effective interventions, particularly for vulnerable populations affected by IDA. Full article

Neuromorphic computing draws inspiration from the brain to design energy-efficient hardware for information processing, enabling highly complex tasks. In neuromorphic computing, chaotic phenomena describe the nonlinear interactions and dynamic behaviors. Chaotic behavior can be utilized in neuromorphic computing to accomplish complex information processing tasks; therefore, studying chaos is crucial. Today, more and more color images are appearing online. However, the generation of numerous images has also brought about a series of security issues. Ensuring the security of images is crucial. We propose a novel fourth-direction hyperchaotic system in this paper. In comparison to low-dimensional chaotic systems, the proposed hyperchaotic system exhibits a higher degree of unpredictability and various dynamic behaviors. The dynamic behaviors include fourth-direction hyperchaos, third-direction hyperchaos, and second-direction hyperchaos. The hyperchaotic system generates chaotic sequences. These chaotic sequences are the foundation of the encryption scheme discussed in this paper. Images are altered by employing methods such as row and column scrambling as well as diffusion. These operations will alter both the pixel values and positions. The proposed encryption scheme has been analyzed through security and application scenario analyses. We perform a security analysis to evaluate the robustness and weaknesses of the encryption scheme. Moreover, we conduct an application scenario analysis to help determine the practical usability and effectiveness of the encryption scheme in real-world situations. These analyses demonstrate the efficiency of the encryption scheme. Full article

Background: We sometimes encounter refractory meningioma cases that are difficult to control, even after achieving a high resection rate or following radiation therapy (RT). In such cases, additional surgical resection might be attempted, but reports regarding outcomes of re-do surgery for recurrent meningiomas are scarce. Methods: This study was a retrospective review of patients who underwent re-do surgery for recurrent meningiomas. The risks of re-doing surgery were statistically analyzed. A comparative analysis between the patients who underwent primary surgery for intracranial meningiomas was also performed. Twenty-six patients underwent re-do surgeries for recurrent meningiomas. Results: At first re-do surgery, gross total resection was achieved in 20 patients (77%). The disease-free survival rate after the first re-do surgery was calculated as 73/58/44% at 1, 2, and 5 years, respectively. A significant factor affecting longer disease-free survival was WHO Grade 1 diagnosis at first re-do surgery (p = 0.02). Surgery-related risks were observed in 10 patients presenting a significant risk factor for skull base location (p = 0.04). When comparing with the risk at primary surgery, the risks of surgical site infection (p = 0.04) and significant vessel injury (p < 0.01) were significantly higher for the re-do surgery. Conclusions: Re-do surgery could increase surgery-related risks compared to the primary surgery; however, it could remain a crucial option, while the indication should be carefully examined in each case. Full article

Technology-enabled state surveillance has evolved rapidly to allow real-time remote tracking and surveillance of people and vehicles and the aggregation of vast amounts of data on people and their movements, networks, and relationships. Facial recognition technology (FRT) comprises a suite of technologies that allows verification, identification, and categorisation by analysing a person’s facial image. Such technologies impact fundamental rights, such as privacy, freedom of expression, and freedom of assembly, but can also be used to detect, investigate, and deter serious crime and harm and to counter threats to security, thus promoting collective interests in security and public safety. These impacts have been considered in terms of scholarship and advocacy, but the shape of principled regulation is less well traversed. This contribution examines three contemporary case studies of the regulation of FRT in policing and security to analyse the challenges in regulating this technology. Full article

Bird identification is a necessary skill for citizen science projects, and teaching and learning about species is essential to halt the decline in biodiversity. Here, we investigated bird species knowledge in a case study of Michigan high school students using an online survey. Participants were asked to identify 21 common species, covering a wide range of orders and families. On average, high school students achieved a correct identification score of 35%. The most well-known species were the American Robin, Blue Jay, Cardinal and Turkey Vulture. We found no difference between boys and girls, but identification scores declined with increasing age. Interest was an important predictor of identification knowledge, as were activities (field trips, outings) both in and out of class. Among species traits, high knowledge of a species was positively related to the number of eBird entries (as a proxy for year-round population size), body mass (heavier species were better known) and internet presence. We suggest expanding this study to other states, and we encourage educators and teachers to improve bird knowledge through birding field trips. Full article

Self-organized criticality is a universal theory for dynamical systems that has recently been applied to the cardiovascular system. Precise methodological approaches are essential for understanding the dynamics of cardiovascular self-organized criticality. This study examines how the duration and quality of data recording affect the analysis of cardiovascular self-organized criticality, with a focus on the beat-by-beat heart rate variability time series obtained from seven healthy subjects in a standing position. Drawing a Zipf diagram, we evaluated the distribution of cardiovascular events of bradycardia and tachycardia. We identified tipping points for the distribution of both bradycardia and tachycardia events. By varying the recording durations (1, 2, 5, 10, 20, 30, and 40 min) and sampling frequencies (500, 250, and 100 Hz), we investigated their influence on the observed distributions. While shorter recordings can effectively capture cardiovascular events, they may underestimate the variables describing their distribution. Additionally, the tipping point of the Zipf distribution differs between bradycardia and tachycardia events. Comparisons of the distribution of bradycardia and tachycardia events should be conducted using long data recordings. Utilizing devices with lower sampling frequencies may compromise data fidelity. These insights contribute to refining experimental protocols and advancing our understanding of the complex dynamics underlying cardiovascular regulation. Full article

The development of micro cracks in shale formations can easily lead to wellbore instability caused by liquid phase invasion. In order to effectively seal the shale micropores, the surface treatment of nano-SiO₂ particles was developed using the silicane coupling agent A-1891. Then, the temperature-sensitive polypenic acrylamide polymer was modified onto the surface of the nanoprocal particle through reaction to obtain the nanosomal blocking agent ASN. The infrared spectrum shows that there are chemical bonds between the generated polymer chains, rather than simple physical composites, indicating the successful synthesis of the temperature-responsive nanosealing agent ASN. The particle size analysis showed that the synthesized nanoparticles in ASN have a uniform particle size distribution and display no agglomeration phenomenon. Applying ASN as a sealing agent in drilling fluid effectively fills the nanoscale micropores and microcracks in shale, making shale denser and significantly improving the wellbore stability of shale formations. In addition, it has good temperature resistance, can adapt to reservoirs at different temperatures, is non-toxic and environmentally friendly, and has good prospects for stable applications in shale formation wellbore. Full article

The present work reports an effective method for the removal of inorganic and organic pollutants using membranes based on different carbonaceous materials. The membranes were prepared based on cellulose acetate (18 wt. %), polyvinylpyrrolidone as a pore-generating agent (2 wt. %) and activated carbon (1 wt. %). Activated carbons were developed from residues after extraction of the mushroom Inonotus obliguus using microwave radiation. It has been demonstrated that the addition of activated carbon to the membranes resulted in alterations to their physical properties, including porosity, equilibrium water content and permeability. Furthermore, the chemical properties of the membranes were also affected, with changes observed in the content of the surface oxygen group. The addition of carbon material had a positive effect on the removal of copper ions from their aqueous solutions by the cellulose–carbon composites obtained. Moreover, the membranes proved to be more effective in the removal of copper ions than iron ones and phenol. The membranes were found to show higher effectiveness in copper removal from a solution of the initial concentration of 800 mg/L. The most efficient in copper ions removal was the membrane containing urea-enriched activated carbon. Full article

Breast cancer, the most frequent malignancy in women worldwide, is a molecularly and clinically very heterogeneous disease. Triple-negative breast cancer is defined by the absence of hormone receptor and growth factor receptor ERBB2/HER2 expression. It is characterized by a more aggressive course of disease and a shortage of effective therapeutic approaches. Hallmarks of cancer cells are not only genetic alterations, but also epigenetic aberrations. The most studied and best understood alterations are methylation of the DNA base cytosine and the covalent modification of histone proteins. The reversibility of these covalent modifications make them attractive targets for therapeutic intervention, as documented in numerous ongoing clinical trials. Epidrugs, targeting DNA methylation and histone modifications, might offer attractive new options in treating triple-negative breast cancer. Currently, the most promising options are combination therapies in which the epidrug increases the efficiency of immuncheckpoint inhibitors. This review focusses exclusively on DNA methylation and histone modifications. In reviewing the knowledge about epigenetic therapies in breast cancer, and especially triple-negative breast cancer, the focus is on explaining concepts and raising awareness of what is not yet known and what has to be clarified in the future. Full article

This study investigates the impact of central bank digital currencies (CBDCs) on monetary policy flexibility, the effective lower bound (ELB), and negative interest rate policies (NIRPs), specifically in the case of the digital euro (DE). Through a combination of theoretical modeling and empirical analysis, including two extensive surveys among EU participants, we explore whether CBDCs can change the ELB and affect consumer preferences in favor of the digital euro over physical cash. Our findings indicate that the introduction of the DE could potentially move the ELB from its current value of around −1.30% by approximately 0.25%. If agents had the possibility to move their deposits into both cash and DE, they would convert approximately 52% of the converted amount into cash and the rest into CBDCs. However, over a 10 year period, the situation would shift in favor of the DE, with a share of 63%. Both findings show that NIRPs will be more limited in the case of the introduction of CBDCs (DE). These facts must be considered both when deciding whether to introduce a CBDC (DE) and after its eventual introduction in the case of NIRP application. Full article

This article employed pupillometry as a non-invasive technique to analyze pupillary light reflex (PLR) using LED flash stimuli. Particularly, for the experiments, only the red LED with a wavelength of 600 nm served as the light stimulation source. To stabilize the initial pupil size, a pre-stimulus (PRE) period of 3 s was implemented, followed by a 1 s stimulation period (ON) and a 4 s post-stimulus period (POST). Moreover, an experimental, low-cost pupillometer prototype was designed to capture pupillary images of 13 participants. The prototype consists of a 2-megapixel web camera and a lighting system comprising infrared and RGB LEDs for image capture in low-light conditions and stimulus induction, respectively. The study reveals several characteristic features for classifying the phenomenon, notably the mobility of Hjórth parameters, achieving classification percentages ranging from 97% to 99%, and offering novel insights into pattern recognition in pupillary activity. Moreover, the proposed device successfully captured the PLR from all the participants with zero reported incidents or health affectations. Full article

Evaluating sea surface temperature (SST) products is essential before their application in marine environmental monitoring and related studies. SSTs from the in situ SST Quality Monitor (iQuam) system, Advanced Microwave Scanning Radiometer 2 (AMSR2) aboard the Global Change Observation Mission 1st-Water, and the Microwave Radiation Imager (MWRI) aboard the Chinese Fengyun-3D satellite are intercompared utilizing extended triple collocation (ETC) and direct comparison methods. Additionally, error characteristic variations with respect to time, latitude, SST, sea surface wind speed, columnar water vapor, and columnar cloud liquid water are analyzed comprehensively. In contrast to the prevailing focus on SST validation accuracy, the random errors and the capability to detect SST variations are also evaluated in this study. The result of ETC analysis indicates that iQuam SST from ships exhibits the highest random error, above 0.83 °C, whereas tropical mooring SST displays the lowest random error, below 0.28 °C. SST measurements from drifters, tropical moorings, Argo floats, and high-resolution drifters, which possess random errors of less than 0.35 °C, are recommended for validating remotely sensed SST. The ability of iQuam, AMSR2, and MWRI to detect SST variations diminishes significantly in ocean areas between 0°N and 20°N latitude and latitudes greater than 50°N and 50°S. AMSR2 and iQuam demonstrate similar random errors and capabilities for detecting SST variations, whereas MWRI shows a high random error and weak capability. In comparison to iQuam SST, AMSR2 exhibits a root-mean-square error (RMSE) of about 0.51 °C with a bias of −0.05 °C, while MWRI shows an RMSE of about 1.26 °C with a bias of −0.14 °C. Full article

In the spring and summer of 1906, while visiting the rural village of Gósol in the Spanish Pyrenees, Picasso executed his first woodcut, made two sculptures out of boxwood, and began to focus on the topoi of wood and the forest as avatars of primal matter and of that which lies beyond civilization. In a subsequent series of paintings, he used wooden supports for images that depict male and female heads that look as if they had been chiseled out of wood. Others represent nude figures in forest settings, with explicitly sexual gestures and poses connoting a range of attitudes. These little studied works provide an optic into Picasso’s early exploration of the emergence of sexual identity as an inner psychic state, but one whose signs can be read through the body. Later, responding to the proliferation of cheap, industrially produced materials, including trompe l’oeil woodgrain wallpaper, Picasso began to treat woodgrain as a mere surrogate, one that marks its distance from actual wood through a variety of painterly and mechanical effects. No longer associated with “primitive” authenticity and the primordial forces of the forest, woodgrain now appears as a false sign open to conceptual play and metamorphosis. Full article

The placenta is the largest fetal organ, which connects the mother to the fetus and supports most aspects of organogenesis through the transport of nutrients and gases. However, further studies are needed to assess placental pathology as a reliable predictor of long-term physical growth or neural development in newborns. The Consensus Statement of the Amsterdam Placental Workshop Group (APWGCS) on the sampling and definition of placental lesions has resulted in diagnostic uniformity in describing the most common pathological lesions of the placenta and contributed to the international standardization of descriptions of placental pathology. In this narrative review, we reclassified descriptions of placental pathology from previously published papers according to the APWGCS criteria and comparatively assessed the relationship with infantile physical and/or neural development. After reclassification and reevaluation, placental pathology of maternal vascular malperfusion, one of the APWGCS criteria, emerged as a promising candidate as a universal predictor of negative infantile neurodevelopmental outcomes, not only in term and preterm deliveries but also in high-risk groups of very low birthweight newborns. However, there are few studies that examined placental pathology according to the full categories of APWGCS and also included low-risk general infants. It is necessary to incorporate the assessment of placental pathology utilizing APWGCS in the design of future birth cohort studies as well as in follow-up investigations of high-risk infants. Full article

Breast cancer and ovarian cancer pose a significant risk for BRCA1 carriers, with limited risk-reduction strategies. While improved screening helps in the early detection of breast cancer, preventive measures remain elusive. Emerging evidence suggests a potential link between iodine levels and modulation of cancer risk, but comprehensive studies are scarce. We conducted a prospective study among 989 BRCA1 carriers to assess the association between blood iodine levels and breast and ovarian cancer risk. Using inductively coupled plasma mass spectrometry, we measured blood iodine levels and observed a negative association with breast cancer risk, with a significantly lower risk observed in quartile 4 (iodine > 38.0 µg/L) compared with quartile 1 (iodine < 30 µg/L) (HR = 0.49; 95%CI: 0.27–0.87; p = 0.01). Conversely, a suggestive increase in ovarian cancer risk was observed at higher iodine levels (HR = 1.91; 95%CI: 0.64–5.67; p = 0.25). No significant association was found between iodine levels and overall cancer risk. Our results suggest the potential of iodine to reduce breast cancer risk in BRCA1 carriers after prophylactic oophorectomy but require further validation and investigation of its effect on ovarian cancer risk and overall mortality. These findings highlight the need for personalized strategies to manage cancer risk in BRCA1 carriers. Full article

Ferulic acid (Fer) and geraniol (Ger) are natural compounds whose antioxidant and anti-inflammatory activity confer beneficial properties, such as antibacterial, anticancer, and neuroprotective effects. However, the short half-lives of these compounds impair their therapeutic activities after conventional administration. We propose, therefore, a new prodrug (Fer-Ger) obtained by a bio-catalyzed ester conjugation of Fer and Ger to enhance the loading of solid lipid microparticles (SLMs) designed as Fer-Ger delivery and targeting systems. SLMs were obtained by hot emulsion techniques without organic solvents. HPLC-UV analysis evidenced that Fer-Ger is hydrolyzed in human or rat whole blood and rat liver homogenates, with half-lives of 193.64 ± 20.93, 20.15 ± 0.75, and 3.94 ± 0.33 min, respectively, but not in rat brain homogenates. Studies on neuronal-differentiated mouse neuroblastoma N2a cells incubated with the reactive oxygen species (ROS) inductor H₂O₂ evidenced the Fer-Ger ability to prevent oxidative injury, despite the fact that it appears ROS-promoting. The amounts of Fer-Ger encapsulated in tristearin SLMs, obtained in the absence or presence of glucose, were 1.5 ± 0.1%, allowing the control of the prodrug release (glucose absence) or to sensibly enhance its water dissolution rate (glucose presence). These new “green” carriers can potentially prolong the beneficial effects of Fer and Ger or induce neuroprotection as nasal formulations. Full article