(1) Background: The diagnosis of lumbosacral radiculopathy involves anamnesis, assessment of sensitivity and strength, diagnostic imaging—usually magnetic resonance imaging (MRI)—and electrodiagnostic testing (EDX), typically electromyography (EMG) and electroneurography (ENG). MRI evaluates the structures supporting the spinal cord, while EDX evaluates root functionality. The present study aimed to analyze the concordance of MRI and EDX findings in patients with clinically suspected radiculopathy. Additionally, we investigated the comparison between these two reference tests and various clinical variables and questionnaires. (2) Methods: We designed a prospective epidemiological study of consecutive cases with an observational, descriptive, cross-sectional, and double-blind nature following the STROBE guidelines, encompassing 142 patients with clinical suspicion of lumbosacral radiculopathy. (3) Results: Of the sample, 58.5% tested positive for radiculopathy using EDX as the reference test, while 45.8% tested positive using MRI. The comparison between MRI and EDX in the diagnosis of radiculopathy in patients with clinical suspicion was not significant; the overall agreement was 40.8%. Only the years with symptoms were comparatively significant between the positive and negative radiculopathy groups as determined by EDX. (4) Conclusion: The comparison between lumbar radiculopathy diagnoses in patients with clinically suspected pathology using MRI and EDX as diagnostic modalities did not yield statistically significant findings. MRI and EDX are complementary tests assessing different aspects in patients with suspected radiculopathy; degeneration of the structures supporting the spinal cord does not necessarily imply root dysfunction.

Multiple sequence alignments and phylogenetic trees are rich in biological information and are fundamental to research in biology. PhyKIT is a tool for processing and analyzing the information content of multiple sequence alignments and phylogenetic trees. Here, we describe how to use PhyKIT for diverse analyses, including (i) constructing a phylogenomic supermatrix, (ii) detecting errors in orthology inference, (iii) quantifying biases in phylogenomic data sets, (iv) identifying radiation events or lack of resolution using gene support frequencies, and (v) conducting evolution-based screens to facilitate gene function prediction. Several PhyKIT functions that streamline multiple sequence alignment and phylogenetic processing—such as renaming FASTA entries or tree tips—are also discussed. These protocols demonstrate how simple command-line operations in the unified framework of PhyKIT facilitate diverse phylogenomic data analysis and processing, from supermatrix construction and diagnosis to gene function prediction.

The platelet count, a component of the full blood count, has been identified as a useful diagnostic marker for cancer in primary care. The reference range for the platelet count is 150 to 400 or 450 × 109/l; this range does not account for natural variation in platelet count by age and sex. This study used three primary care cohorts from England Canada, and Australia. Patients aged 40 years and over with a full blood count were included and stratified by age (in 10-year bands), sex, (male/female), and platelet count group. Cancer incidence within one year of test date was estimated from linked registry data. In all three countries there was a clear upwards trend in cancer incidence with increasing platelet count, for both sexes and at all age groups. Lung and colorectal were the most common sites. These results have important implications for the international application of this work; analysis of local health datasets will be crucial to determine appropriate thresholds. Appropriate upper thresholds will depend on local populations, healthcare needs, and priorities. Further research is needed to assess the likely impact of new recommendations on the healthcare system, on cancer outcomes, and patient benefit.

A comprehensive study of the interactions of human serum albumin (HSA) and α-1-acid glycoprotein (AAG) with two isoquinoline alkaloids: allocryptopine (ACP) and protopine (PP) was performed. The UV-Vis spectroscopy, molecular docking, competitive binding assays, and circular dichroism (CD) spectroscopy were used for the investigations. The results showed that ACP and PP form spontaneous and stable complexes with HSA and AAG, with ACP displaying a stronger affinity towards both proteins. Molecular docking studies showed also revealed the preferential binding of ACP and PP to specific sites within HSA, with site 2 (IIIA) being identified as the favored location for both alkaloids. This was supported by competitive binding assays using markers specific to HSA's drug binding sites. Similarly, for AAG, a decrease in fluorescence intensity upon addition of the alkaloids to AAG/ Quinaldine Red (QR) complexes indicated the replacement of the marker by the alkaloids, with ACP showing a greater extent of replacement than PP. CD spectroscopy showed that the proteins’ structures remained largely unchanged suggesting that the formation of complexes did not significantly perturb the overall spatial configuration of these macromolecules. These findings are crucial for advancing the knowledge on the natural products-protein interactions and the future design of isoquinoline alkaloid-based therapeutics.

The release of the active substance from the matrix modified-release tablets based on Kollidon®SR and chitosan depends on its solubility in the dissolution medium and on the composition of the matrix-forming polymers. The study is based on new oral matrix tablets based on Kollidon®SR and chitosan, formulated to optimize the low oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug, a class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method, and their combination at 1:1, 1:2, 1:3 chlorzoxazone/ excipients, 20%-40% (w/w) Kollidon®SR, 3-7% (w/w) chitosan and the auxiliary substances were formulated in constant concentrations. Pharmaco-technical characterization included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, Carr Index), and of pharmaco-chemical characteristics (mass and dose uniformity, thickness, diameter, mechanical strength, Friability, degree of softening, in vitro release profile) of the tablets. Based on the initial evaluation of the pharmaco-technical analysis, pharmaco-chemical characteristics, and in vitro release profile, only three matrix tablet formulations (F1b, F2b, and F3b) were further tested. They were evaluated through Fourier-transform infrared spectrometry, X-ray Diffraction, thermogravimetry, differential scanning calorimetry, and in vitro dissolution tests. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified release oral formulations. In vitro kinetic study reveals a complex mechanism of release occurring in the first (0 - 2 hours) and second (2.0 hours – 36 hours) steps of drug release. Two factors have been calculated to assess the release profile of chlorzoxazone: f1 - the similarity factor and f2 - the factor difference. The results have shown that both Kollidon®SR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. In vitro dissolution tests revealed the F2b sample, data suggesting a faster drug release. The three formulations showed optimum pharmaco-technical properties and in vitro kinetic study, and they had tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone.

Abstract: Congenital cytomegalovirus (cCMV) infection poses significant risks to fetal development, particularly affecting the nervous system. This study reports a fetal autopsy case, examining cCMV infection and focusing on CMV DNA measurements in various fetal organs before formalin fixation, a novel approach for comprehensive CMV DNA evaluations in fetal organs affected by cCMV. A 20-week-old male fetus was diagnosed with cCMV following the detection of CMV DNA in ascites obtained via abdominocentesis in utero. After termination of pregnancy, multiple organs of the fetus, including the cerebrum, thyroid gland, heart, lungs, liver, spleen, kidneys, and adrenal glands, were extracted and examined for CMV DNA loads using real-time polymerase chain reaction. Histopathological examination involved hematoxylin-eosin and CMV-specific immunostaining. A correlation was found between CMV DNA loads and pathology, with higher CMV-infected cell numbers observed in organs positively identified with both staining methods, exhibiting CMV DNA levels of ≥1.0 × 104 copies/mL, compared to those detected solely by CMV-specific immunostaining, where CMV DNA levels ranged from 1.0 x 103 to 1.0 x 104 copies/mL. These results highlight a quantifiable relationship between organ infection extent and CMV DNA concentration, providing insights into cCMV pathogenesis and potentially informing future diagnostic and therapeutic strategies for cCMV infection.

One of the main challenges of cultured meat is reducing the costs of production, often described as scaling. The main components of the cultivation process include: cells, media, scaffolds and bioreactors. This work presents an alternative to current stainless steel or glass bioreactors and uses food-grade plant-based scaffolds. Bioreactors must be sterile and leak-free to maintain a proper environment for cell growth. Thermoplastic films are a popular material for constructing these fluidic systems, but traditional methods of welding these film are expensive and do not allow rapid prototyping resulting in high research and development costs for companies. In this study, a laser welding method was developed to join thermoplastic films in a way that prevents contamination and leaks, affording effective macro-fluidics fabrication. This technique was tested using polyethylene (PET) films and a laser cutter operating with settings calibrated for the material to be welded or cut. The laser welding method was found to produce strong, leak-free seals in PET films with minimal heat-induced damage to the films. The ability to design fluidics, chambers and ports of various size. Using this method afforded the incorporation of plant-based scaffolds from food-grade plants (Rice). The laser welding method developed in this study provides a reliable, contamination-free method for the rapid fabrication of fluidic systems for cell cultivation. This technique has the potential to be compatible with a vast range of cell types and scaffolds and to be widely adopted in tissue engineering for regenerative medicine and food applications such as cultured meat.

Lung cancer is the leading cause of cancer related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterised by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation with their metabolic pathways and in light of the altered cancer metabolism.

Two coupled climate models which participated the CMIP6 project (Coupled Model Intercomparison Project Phase 6), the Earth System Model of Chinese Academy of Sciences version 2 (CAS-ESM2-0) and the Nanjing University of Information Science and Technology Earth System Model version 3 (NESM3), were assessed in terms of the impact of four new sea ice parameterization schemes. These four new schemes are related to air-sea heat flux, radiation penetration and absorption, melt ponds, ice-ocean flux, respectively. To evaluate the effectiveness of these schemes, key sea ice variables with and without these new schemes, such as sea ice concentration (SIC) and sea ice thickness (SIT), were compared against observation and reanalysis product from 1980 to 2014. The simulations followed the design of historical experiments within the CMIP6 framework. The results revealed that both models demonstrated improvements in simulating Arctic SIC and SIT when the new parameterization schemes were implemented. The model bias of SIC in some marginal sea ice zones of Arctic was reduced, especially during March. The SIT was increased and the transpolar gradient of SIT was reproduced. The changes of spatial pattern of SIC and SIT after adding new schemes bear similarities between the two coupled models. This suggests that the new schemes have potential for broad application in climate models, especially for those with underestimated SIT.

Our aim was to determine the secondary antibody deficiency profiles of patients in a mesoregion of São Paulo state, Brazil, focusing on infectious diseases. Demographic characteristics, clinical and laboratory data were obtained from electronic files; infections were classified as organ-specific and graded as mild, moderate, life-threatening, and fatal. Non-Hodgkin lymphoma (NHL) accounted for 30% of patients, nephrotic syndrome (NS) 25%; chronic lymphocyte leukemia 20%, and multiple myeloma 15%. Patients with NS were younger than those in other groups, and hypo-γ-globulinemia was detected in 94.1%, IgG <400 mg/dL in 60.0%, IgA <40 mg/dL in 55.0%, and CD19 <20 cells/mm³ in 30.0%. One hundred and one infections were found; 82.1% were classified as mild or moderate, 7.9% as life-threatening, and 1.9% as fatal. Respiratory tract infections were more prevalent (41.5%), and pneumonia accounted for 19.8%. Lower levels of infections were found in patients with NS compared with NHL (P=0.0001). Most patients progressed to hypo-γ-globulinemia and secondary antibody deficiency after treatment with immunosuppressants, and mild and moderate infections were predominant. These therapies are increasing in patients with different diseases, therefore monitoring hypo-γ-globulinemia and infections may help to identify patients at high risk for severe complications, antibiotic prophylaxis or treatment, and immunoglobulin replacement

The results of shaking table tests from previous studies on a one-story, two-bay reinforced concrete frame—exhibiting both shear and axial failures—were compared with nonlinear dynamic analyses using simplified models intended to evaluate the collapse potential of older reinforced concrete structures. To replicate the nonlinear behavior of columns, whether shear-critical or primarily flexure-dominant, a one-component beam model was applied. This model features a linear elastic element connected in series to a rigid-plastic, linearly hardening spring at each end, representing a concentrated plasticity component. To account for strength degradation through path-dependent plasticity, a negative slope model as degradation was implemented, linking points at both shear and axial failure. The shear failure points were determined through pushover analysis of shear-critical columns using the Phaethon software. Although the simplified model provided a reasonable approximation of the overall frame response and lateral strength degradation especially in terms of drift, its reduced computational demands led to some discrepancies between the calculated and measured shear forces and drifts during certain segments of the time-history response.

This study introduces a fresh approach to boost the security and accuracy of predicting photovoltaic (PV) power generation using secure aggregation techniques. The author will focus on several key stages in the PV data lifecycle, such as collecting, transmitting, storing, and analyzing data. To protect against potential attacks and prevent information leaks during these four crucial processes, we use Paillier and BVG homomorphic encryption methods. By combining TLS protocol with edge computing during data transmission, we not only improve data security but also reduce latency while tackling threats from attackers. There are two different types of attackers: honest but curious adversaries and active adversaries. Additionally, we make strategies for key management, access control, and auditing to ensure that access to information is monitored to help enhance overall system security. In the final phase of analyzing and predicting PV power output, we utilize advanced models like LSTM networks and CEEMDAN to achieve precise time-series predictions. The results indicate that these methods can effectively manage large PV datasets while keeping high prediction accuracy alongside strong security measures. The research establishes a foundation for improving homomorphic encryption, enhancing key management, and creating a big data security framework specific to photovoltaic energy production.

Ectomycorrhizal (EM) associations are essential symbiotic relationships that contribute significantly to the health and functioning of forest ecosystems. This review examines the biotic factors that influence EM associations, focusing on plant and fungal diversity, host specificity, and microbial interactions. Firstly, the diversity of host plants and ectomycorrhizal fungi (EMF) is discussed, highlighting how the richness of these organisms affects the formation and success of EM symbioses. Next, host specificity is explored, with a focus on the complex relationships between EMF and their host plants. Microbial interactions are examined in depth, with sections on both positive and negative influences of bacteria and different fungal groups on EM formation. Overall, this review provides a comprehensive overview of the biotic factors that shape EM associations, offering insights into the mechanisms that underpin these critical ecological interactions and their broader implications for ecosystem management and restoration.

The dispersive and polar properties of materials, and especially of polymers and copolymers play an important role in several engineering applications implying their surfaces and interfaces. The surface energetic properties of poly(styrene-co-butadiene) have never been studied. We proposed in this study an accurate determination of such properties by using the inverse gas chromatography (IGC) at infinite dilution. Background: The IGC surface technique led to the dispersive and polar properties of poly(styrene-co-butadiene) rubber (SBR) by adsorption of organic solvents at various temperatures. Methods: Our new methodology based on the thermal Hamieh model and the London dispersion interaction energy was used to determine the London dispersion surface energy, the polar acid-base surface energy, and the Lewis acid-base properties of the copolymer. Results: The different surface energy parameters of the SBR were obtained as a function of temperature from the chromatographic measurements. Conclusions: The dispersive and polar free energies of adsorption of the various n-alkanes and polar molecules on poly(styrene-co-butadiene) were determined at different temperatures. A decrease of the London dispersive surface energy and the polar Lewis acid-base surface energies of SBR was highlighted when the temperature increased. It was showed a Lewis amphoteric character of poly(styrene-co-butadiene) with a highest basic constant 10 times larger than its acidic constant.

Free vibration calculations of Sandwich plates with curvilinear fiber variable stiffness composite face sheets usually require a significant computing effort to obtain a high computational accu-racy. In order to get the natural frequencies of sandwich plates with high computational accuracy and low computational cost, an improved approach integrating the differential quadrature method (DQM) and first-order shear deformation theory (FSDT) is introduced in this work. The skins of sandwich plates are composed of one or several layers of variable stiffness composite laminates (VSCL) with fiber paths assumed to follow a specific linear pattern. The FSDT and von Kármán strain–displacement relationship were used to derive the governing equations of the sandwich plate, and DQM was applied to discretize such governing equations and solve for the fundamental frequency of the sandwich plate. The computational results were verified and compared with other FSDT–based computational results, and there was good agreement with the suggested model. Also, the variation patterns of the natural frequency under different pa-rameters such as fiber orientation angles, boundary conditions, number of layers, and core/skin thickness were investigated. This study entailed the development of an efficient solution to the problem of the fundamental frequency of VSCL sandwich plates, and the outcomes could pro-vide a basis for future dynamics comparative studies.

Type I (IFN-α/β) and Type III (IFN-λ) interferon-inducible myxovirus resistance (Mx) proteins have long been recognized to inhibit a broad spectrum of RNA- and DNA-containing viruses (1-5). Mx proteins are dynamin-family GTPases of size 60-70 kDa (1-3) with different subcellular localization and antiviral activities. In the last 5 years there has been a paradigm shift in our understanding of the structures formed by human and murine Mx proteins in the cytoplasm and nucleus. We now recognize that the major human MxA protein forms structures in the cytoplasm and the major murine Mx1 forms structure in the nucleus which comprise liquid-liquid phase separated (LLPS) biomolecular condensates [membraneless organelles (MLOs)] with a gel-like internal consistency. The second human Mx protein, MxB, which had been previously observed to associate with the cytoplasmic face of nuclear pores, was also recently confirmed to represent cytoplasmic biomolecular condensates. Our overall focus now is to understand the formation, dynamics and antiviral function of biomolecular condensates of different Mx proteins in the cytoplasm and nucleus in cells of different species. We highlight the metastability and rapidly reversible hypotonicity sensing properties of MxA condensates in human cells, especially as applicable to environmental stress inflicted on the oral mucosa.

Previous high throughput screening studies indicated trans-eQTLs tend to be tissue specific. In this study, I probed if this feature can be used to identify tissue-specific gene regulatory networks. eQTL data (P<5e-8) for 16,259 genes were identified and their summary association statistics were obtained from the eQTLGen database. Next, eQTLs that display both cis and trans regulatory effects were selected and the association between their corresponding genes were examined by Mendelian randomization. 253 genes that exerted trans-regulatory impacts on 1,439 genes were identified. Majority of the identified gene-pairs aggregated into a gene regulatory network significantly enriched in hemo-immune processes. The robustness of finding was confirmed through simulation. Genes with higher gene expression heritabilities displayed broader regulatory impact in the network. The network displayed the scale-free topology, this provided the reason to examine the association of the network’s hub genes with the phenome. The outcome of analyses revealed GSDMB and ORMDL3 impact several disorders of immune origin and higher expression of HHEX is associated with lower triglycerides and risk of type 2 diabetes. This study reports trans-eQTLs can be used to identify tissue-specific gene regulatory networks and describes a workflow to achieve this purpose. The identified network displayed scale-free topology indicating the hub genes of a tissue-specific network could be targeted to prevent disease outcomes.

The linear diblock copolymer polystyrene-b-poly(4-vinylpyridine) (PS-P4VP) is an important copolymer recently used in many applications such as optoelectronics, sensors, catalysis, membranes, energy conversion, energy storage devices, photolithography, and biomedical applications. (1) Background: The surface thermodynamic properties of PS-P4VP copolymer are of great importance in many chemical and industrial processes. (2) Methods: The inverse gas chromatography (IGC) at infinite dilution was used for the experimental determination of the retention volumes of organic solvents adsorbed on copolymer surfaces as a function of temperature. This led to the variations of the free energy of interaction necessary to the evaluation of the London dispersive and polar acid-base surface energies, the polar enthalpy and entropy, the Lewis acid-base constants, and the transition temperatures of PS-P4VP copolymer. (3) Results: The application of the thermal Hamieh model led to accurate determination of the London dispersive surface energy of the copolymer that showed non-linear variations versus the temperature highlighting the presence of two transition temperatures. It was observed that the Lewis’s acid-base parameters of the copolymer strongly depend on the temperature and the Lewis base constant of the solid surface was showed to be higher than the its acid constant. (4) Conclusions: Un important effect of the temperature on the surface thermodynamic properties of PS-P4VP was proved and new surface correlations were determined.

Weathering and erosion transport minerals and organics toward the sea or lake bottoms over geologic time. The finest solids are deposited in lower, less turbulent areas, such as lake bottoms and continental shelves. They sometimes stack up to thicknesses of kilometers, and begin compacting. These sediment sections are called shales, and as initially deposited in water, shales can have porosities up to 50-80{\%} water, As they are buried, many alteration products from oil to slate are produced due to overburden and temperature increasess, making them important to study. A preceeding paper \cite{1} showed that pressure solution is the primary mechanism for porosity reduction, with possible mechanical compaction at shallow depths. Without naming the mineral(s) involved, it postulated that the greater the product of the water and pore interfaces, the faster the reaction would proceed. This term is $ \varphi^{4m/3}(1-\varphi)^{4n/3}$ , where $\varphi$ is porosity and m and n are numbers close to unity. The large exponents, {\em 4/3}, recognize that the reaction occurs at the molecular scale at which the surfaces are rough. A second term, $\exp^{(-E/RT)}$ , indicates that the reaction is impeded by a quantum energy barrier, E, with diminished impeding power as increased available thermal energy, represented by the absolute temperature, T, becomes available at greater depths in the Earth. These two factors combine to allow porosity $\varphi$ to reduce with time, or equivalently for the fraction of solids, $(1-\varphi)$, to increase with time,$\left. \frac{\partial(ln(1-\varphi) ) }{\partial t } \right |_{\sigma} = (\varphi )^{4m/3}( 1-\varphi )^{4n/3}Ae^{-E/(RT)}$. { \em Here it is shown that this equation can cover quantitatively any actual deposition rates which may have been experienced by the six sections studied, the actual deposition rates being unknown for these cases. Hence a time-depth depositional history for any new shale section, known in detail, would allow determination of the parameters m, n, E and a lumped proportionality constant A. This was accomplished by showing that, for a wide range of depositional rates, r, the range of E for any of the studied sections is small compared to laboratory measurements of quartz solution\cite{2}, 24+-15kJ/mol. Results were obtained over this range of r's using the previously determined m and n, and porosity and temperature profiles. The presently existing porosity profiles necessarily incorporate any overpressure or underpressure conditions that may have existed in the past or currently, as the net difference between overburden and pore pressure is a primary driving force for pressure solution. $SiO_2$ usually comprises 20-50{\%} of shales. In conclusion, pressure solution of quartz can account for vertical compaction of shales quantitatively in the studied examples. Separately, a quasi-eqivalent method for discussing reduced porosities in Macron 2 versus Macron 1 as increased vertical stress, rather than additional horizontal stress, is illustrated. Experiments are suggested to clarify the pressure solution mechanism. The role of horizontal forces is discussed. From a global point of view, shale compaction by pressure solution is a quantified step in the cycling of continental rocks, beginning with rifting.

Hydroperoxides (ROOH) are known as damaging agents capable of mediating mutation, while a role as signaling agents through oxidation of protein sulfhydryls that can alter cancer-related pathways has gained traction. Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme that reduces ROOH at the expense of glutathione (GSH). GPX2 is noted for a tendency of large in-creases or decreases in expression levels during tumorigenesis that leads to investigators focusing on its role in cancer. However, GPX2 is only one component of multiple enzyme families that metabolize ROOH and GPX2 levels are often very low in the context of these other ROOH reducing activities. Colorectal cancer (CRC) was selected as a case study for examining GPX2 function as colorectal tissues and cancers are sites where GPX2 is highly expressed. A case can be made for a significant impact of changes in expression levels. There is also a link between GPX2 and NADPH oxidase 1 (NOX1) from earlier studies that is seldom addressed and is discussed, presenting data on a unique association in colon and CRC. Tumor-derived cell lines are quite commonly used for pre-clinical studies involving the role of GPX2 in CRC. Generally, selection for this type of work is limited to identifying cell lines based on high and low GPX2 expression with the standard re-search scheme of overexpression in low expressing lines and suppression in high expressing lines to identify impacted pathways. This overlooks CRC subtypes among cell lines involving a wide range of gene expression profiles and a variety of driver mutation differences along with a large difference in GPX2 expression levels. A trend for low and high GPX2 expressing cell lines to segregate into different CRC subclasses, indicated in this report, suggests that choices based solely on GPX2 levels may provide misleading and conflicting results by disregarding other properties of cell lines and failing to factor in differences in potential protein targets of ROOH. CRC and cell line classification schemes are presented here that were intended to assist workers in performing pre-clinical studies but are largely unnoted in work on GPX2 and CRC. Studies are often initiated on the premise that the transition from normal to CRC is associated with up-regulation of GPX2. This is probably correct. However, the source normal cells for CRC could be almost any colon cell type, some with very high GPX2 levels. These factors are addressed in this study.

Post-traumatic stress disorder (PTSD), a mental disorder caused by exposure to traumatic stress, affects 5-10% of the world’s population. PTSD is associated with several medical and neurological comorbidities. It has been suggested that these are due to accelerated aging, and that changes in telomere length (TL) and telomerase enzyme activity may serve as biomarkers of this process. Early research in this field suggested that TL was significantly reduced in PTSD. The current review was conducted to provide a critical analysis of recent clinical and translational research on telomere length and telomerase in PTSD. The results of 26 clinical studies suggest that TL in PTSD is highly variable, and may be influenced by methodological, demographic, trauma-related and psychosocial factors. There is no evidence for altered telomerase activity in PTSD, though this was hypothesized by earlier workers in the field. Translational research suggests that exposure to traumatic stress does lead to TL shortening. Overall, it is likely that TL in PTSD depends on several variables that are specific to individuals and groups. Other markers of cellular aging, such as epigenetic changes, may be more specific indices of accelerated aging in patients with PTSD.

Cementitious materials exhibit excellent binding properties and micropore structures that support the stabilization of TiO2 nanoparticles within the matrix. Therefore, these materials are ideal for the development of functional construction products with TiO2 nanoparticles. This study investigated the degree of hydration, microstructure, and mechanical properties of cement-containing TiO2 nanoparticles. The experimental results demonstrated that TiO2 nanoparticles accelerated the hydration rate of cement, reducing the setting times. Moreover, TiO2 nanoparticles changed matrix microstructure, decreasing the porosity and improving early-age strength. Although TiO2 nanoparticles function as nucleation sites in the cement hydration reaction, the tendency of the particles to clump implies that proper dispersion should be ensured when mixing in large quantities. When developing new building materials incorporating TiO2 nanoparticles, considering the effect of TiO2 nanoparticles on the hydration reaction of cementitious materials is crucial.

In this study, a novel method is proposed to estimate surface-spectral reflectance from camera responses that combines model-based and training-based approaches. An imaging system is modeled using the spectral sensitivity functions of an RGB camera, spectral power distributions of multiple light sources, unknown surface-spectral reflectance, additive noise, and a gain parameter. The estimation procedure comprises two main stages: (1) selecting the local optimal reflectance dataset from a reflectance database and (2) determining the best estimate by applying a neural network to the local optimal dataset only. In stage (1), the camera responses are predicted for the respective reflectances in the database, and the optimal candidates are selected in the order of lowest prediction error. In stage (2), most reflectance training data are obtained by a convex linear combination of local optimal data using weighting coefficients based on random numbers. A feed-forward neural network with one hidden layer is used to map the observation space onto the spectral reflectance space. In addition, the reflectance estimation is repeated by generating multiple sets of random numbers, and the median of a set of estimated reflectances is determined as the final estimate of the reflectance. Experimental results show that the estimation accuracies exceed those of other methods.

Hypertension is a frequent risk factor for cardiovascular diseases and the prevalence rate is continuously rising. Multiple pathophysiological mechanisms are responsible for hypertension, necessitating a combination of drugs from different classes for best management. Combination therapy is five times more effective in decreasing blood pressure compared to escalating the dose of a single agent. As per the ACCOMPLISH trial analysis, coupling a renin-angiotensin system inhibitor with a calcium channel blocker is more effective than the combination of a renin-angiotensin system inhibitor with diuretics in reducing major cardiovascular events, cardiovascular-related mortality, and the progression of chronic kidney disease. The renin-angiotensin system can be suppressed by inhibiting the angiotensin-converting enzyme or angiotensin type 1 receptor (AT1R), resulting, in decreased vascular smooth muscle contraction, heart performance, and reduced aldosterone synthesis. Calcium channel blockers work by inhibiting L-type calcium channels, reducing heart performance via negative inotropic, chronotropic, and bathmotropic effects, along with reducing vascular smooth muscle contraction. Diuretics exert their antihypertensive impact by changing body fluid volume and electrolytes. Initially, hypertension treatment commences with a single medication but often, different classes of two or more antihypertensive medications are necessary for achieving the target blood pressure goal. Sometimes, for Resistant hypertension four different classes of antihypertensive medications are necessary to reach the target blood pressure goal.

The rapid advancements in satellite technology have led to a significant increase in high-resolution remote sensing (RS) images, necessitating advanced processing methods. Additionally, a patent analysis revealed a significant increase in deep learning and machine learning applications in remote sensing, highlighting the growing importance of these technologies. Therefore, this paper introduces the Kolmogorov-Arnold Network (KAN) model to remote sensing, aiming to enhance efficiency and performance in RS applications. We conducted several experiments to validate KAN's applicability, starting with the EuroSAT dataset, where we combined the KAN layer with multiple pretrained CNN models. The optimal performance was achieved with ConvNeXt, leading to the development of the KonvNeXt model. KonvNeXt was evaluated on the Optimal-31, AID, and Merced datasets for validation, and it achieved accuracies of 90.59%, 94.1%, and 98.1%, respectively. The model also showed fast processing speed, with the Optimal-31 and Merced datasets completed in 107.63 seconds each, while the bigger and more complicated AID dataset took 545.91 seconds. This result is meaningful since it achieved faster speeds and comparable accuracy compared to the existing study which utilized VIT and proved KonvNeXt's applicability for remote sensing classification tasks. Furthermore, we investigated the model's interpretability by utilizing Occlusion Sensitivity and by displaying the influential regions, it validated its potential use in a variety of domains including medical imaging and weather forecasting. This paper is meaningful in that it is the first use of KAN in remote sensing classification, proving its adaptability and efficiency.

The teaching of mathematics at the Faculty of Military Technology of the University of Defense in the first two years of the five-year Military master’s degree is divided into the teaching of students in four specializations: Military Technologies – Mechanical, Military Technologies – Electrical, Military Geography and Cartography, and Cybersecurity. The article discusses the previous five-year experience in teaching the subjects Mathematics I, Mathematics II, Mathematics III, and Graph theory for the specialization in Cybersecurity, that the author of the paper gained while teaching, as a guarantor of these four subjects. The article provides an overview of the topics that are covered, typical exam assignments, and an evaluation of the results of the semester exams in the five years since the accreditation of the Cybersecurity specialization was granted.

Clustered regularly interspaced short palindromic repeats (CRISPR) based gene-editing has begun to transform the treatment landscape of genetic diseases. The history of the discovery of CRISPR/CRISPR-associated (Cas) proteins/single guide RNA (sgRNA)-based gene-editing since the first report of repetitive sequences of unknown significance in 1987 is fascinating, instructive, and inspiring for future advances. The recent approval of CRISPR-Cas9-based gene therapy to treat patients with severe sickle cell anemia and transfusion-dependent beta thalassemia has renewed hope for treating other hematologic diseases, including patients with germline predisposition to hematologic malignancies, who would benefit greatly from the development of CRISPR-based gene therapies. The purpose of this manuscript is three-fold: first, a chronological description of the history of CRISPR-Cas9-sgRNA-based gene editing; second, a brief description of the current state of clinical research in hematologic diseases, including selected applications in treating hematologic diseases with CRISPR-based gene therapy; and third, the current progress in gene therapies in inherited hematologic diseases and bone marrow failure syndromes, to hopefully stimulate efforts towards developing these therapies for patients with inherited bone marrow failure syndromes and other inherited conditions with germline predisposition to hematologic malignancies.

The thermal surface properties of graphenes and carbon materials are of crucial importance in chemistry of materials, chemical engineering, and many industrial processes. (1) Background: The determination of these surface properties is carried out using inverse gas chromatography at infinite dilution which leads to the retention volume of organic solvents adsorbed on solid surfaces. This experimental and fundamental parameter actually reflects the surface thermodynamic interactions between injected probes and solid substrates. (2) Methods: The London dispersion equation and the Hamieh thermal model were used to quantify the London dispersive and polar surface energy of graphenes and carbon fibers as well their Lewis acid-base constants by introducing the coupling amphoteric constant of materials. (3) Results: The London dispersive and polar acid-base surface energies, the free energy of adsorption, the polar enthalpy and entropy, and the Lewis acid-base constants of graphenes and carbon materials were determined. (4) Conclusions: it was showed that graphene exhibited the highest values of London dispersive surface energy, polar surface energy, and Lewis’s acid-base constants. These highest characteristics of graphene justify its great potentiality and uses in many industrial applications.

The global steel industry is a major contributor to greenhouse gas emissions, and the adoption of green hydrogen in Direct Reduced Iron (DRI) production has the potential to significantly reduce CO2 emissions and support climate targets. This review explores the environmental, economic, technological, and social implications of using green hydrogen in DRI processes. The findings suggest that green hydrogen can reduce emissions by up to 90% compared to traditional methods, enhance energy security, and stimulate local economic development. However, high initial costs, energy efficiency concerns, and social acceptance issues remain significant barriers. The review also highlights the importance of integrating carbon capture and storage technologies, addressing logistical challenges, and considering the geopolitical implications of a shift towards green hydrogen. Green hydrogen presents a promising solution for decarbonising the steel industry but continued research, investment in infrastructure, and strategic planning are essential to overcome the challenges and drive widespread adoption.

We consider fractional integral operators $(I-T)^d, d \in (-1,1)$ acting on functions $g: \mathbb{Z}^{\nu} \to \mathbb{R}, \nu \ge 1 $, where $T $ is the transition operator of a random walk on $\mathbb{Z}^{\nu}$. We obtain sufficient and necessary conditions for the existence, invertibility and square summability of kernels $\tau (\mathbf{s}; d), \mathmb{s} \in \mathbb{Z}^{\nu}$ of $(I-T)^d $. Asymptotic behavior of $\tau (\mathbf{s}; d)$ as $|\mathbf{s}| \to \infty$ is identified following local limit theorem for random walk. A class of fractionally integrated random fields $X$ on $\mathbb{Z}^{\nu}$ solving the difference equation $(I-T)^d X = \varepsilon$ with white noise on the right-hand side is discussed, and their scaling limits. Several examples including fractional lattice Laplace and heat operators are studied in detail.

Microglial cells are brain macrophages that support and protect the central nervous system enviroment. Aging induces alterations in microglial polarization, resulting in a shift towards a neurotoxic phenotype characterized by increased expression of pro-inflammatory markers. Dysregulation of microglial cells regulatory pathways and interactions with neurons contribute to chronic activation and neurodegeneration. A better understanding the involvement of microglia in neurodegenerative diseases like Alzheimer's and Parkinson's, is a critical topic to studying the role of inflammatory responses in disease progression. Furthermore, the metabolic changes in aged microglia, including downregulation of oxidative phosphorylation are discussed in this review. Understanding these mechanisms is crucial for developing better preventive and therapeutic strategies.

Academics in healthcare grapple with the challenge of efficiently managing time while addressing diverse roles and responsibilities, leading to heightened levels of anxiety and stress within the academic community. The primary objective of this study is to offer a sustainable and systemic solution to the prevalent time-management challenges in healthcare academia, through the development of a predictive model. Employing systemic analysis software and adopting a systemic management approach, we crafted a model to address academic time-management concerns. The dynamics of time allocation for academicians are governed by three fundamental pillars: teaching, research, and administrative tasks. Significantly prioritizing administrative tasks depletes valuable academic time, making time management within academia excessively costly. This occurs as highly skilled individuals find themselves diverted towards administrative duties at the expense of their academic roles diminishing resilience levels. The proposed Timebooster Academic Systemic Model (TASM) advocates for the cultivation of soft skills in academia, en-compassing prioritization, seeking assistance, and addressing tendencies of perfectionism and procrastination. Additionally, TASM recommends the implementation of full automation, delegation of administrative responsibilities, and the mitigation of both overt and covert time-consuming elements. Furthermore, TASM reports on the pivotal role of the academic resilient manager-leaders, who actively contribute to their own satisfaction and academic growth by enhancing collaboration and teamwork. Time-management challenges emerge as a critical determinant of academic well-being and resilience. Systemic models, exemplified by TASM, offer a valuable framework for investigating prioritization concerns, identifying administrative impediments in academic processes, and managing low-value time-consuming elements. The TASM model, along with the systemic philosophy underpinning its design, presents an avenue for advancing the exploration of time-management phenomena within the context of healthcare academia.

Inverse gas chromatography at infinite dilution was used to determine the surface thermodynamic properties of silica particles and PMMA adsorbed on silica, and more particularly, to quantify the London dispersive energy γsd, the Lewis acid γs+ and base γs- polar surface energies of PMMA/silica composites as a function of the temperature and the recovery fraction θ of PMMA. The polar acid–base surface energy γsAB and the total surface energy of the different composites were then deduced as a function of the temperature. In this paper, the Hamieh thermal model was used to quantify the surface thermodynamic energy of poly methyl methacrylate (PMMA) adsorbed on silica particles at different recovery fractions. A comparison of the new results was carried out with those obtained by applying other molecular models of the surface areas of organic molecules adsorbed on the different solid substrates. An important deviation of these molecular models from the thermal model was proved. The determination of γsd, γs+, γs-, and γsAB of PMMA in both bulk and adsorbed phases showed an important non-linearity variation of these surface parameters as a function of the temperature. The presence of maxima in the curves of γsd(T) highlighted the second order transition temperatures in PMMA showing beta-relaxation, glass transition and liquid-liquid temperatures. These three transition temperatures depended on the adsorption rate of PMMA on silica. The proposed method gave a new relation between the recovery fraction of PMMA and its London dispersive energy showing an important effect of the temperature on the surface energy parameters of adsorption of PMMA on silica. A universal equation relating γsd(T,θ) of the systems PMMA/silica to the recovery fraction and the temperature was proposed.

There are rich proper noun derivative semantic relationships in geographic entity vector data. The identification of traditional proper noun derivative semantic relationships usually requires toponym researchers to examine the source of derived toponyms by consulting a large number of toponym documents. This method cannot adapt to the mining of proper noun derivative semantic relationships for large-scale geographical entity. In this regard, this paper proposes a method of identifying the proper noun derivative semantic relationships for geographical entity by combining prompt learning and XGBoost model. This method transforms the extraction problem of proper noun derivative semantic relationships into a binary classification problem by analyzing the characteristics of the derivation relationship of toponyms in the form of toponyms and the spatial and temporal distribution of geography. Firstly, prompt learning and gaussian mixture model are used to extract and cluster the derivation words of toponyms, so as to realize the recognition of derived toponyms collections. Then, enumerate the possible proper noun derivations in the toponym set, and then the XGBoost model is used to identify the semantic relations derived from the proper noun of geographical entities. In the experiment, the recognition method of proper noun derivative semantic relationships based on prompt learning and XGBoost proposed in this paper has achieved good relationship recognition effect in the experiment. This method has certain practical value in the fields of toponym management and toponym translation.

This research was devoted to study the effect of the tacticity of PMMA on the surface physicochemical properties such as the London dispersive component of the surface energy of the polymer, the polar and dispersive free energies, the Lewis’s acid-base surface parameters, and the Lewis acid and base surface energies of atactic, isotactic and syndiotactic PMMAs as a function of the temperature. Inverse gas chromatography (IGC) at infinite dilution was used to determine the surface thermodynamic properties of PMMA at different tacticities. The experimental values of the net retention time and volume of model organic molecules adsorbed on the atactic, isotactic and syndiotactic PMMAs, were obtained by IGC technique at infinite dilution. The London dispersion interaction energy was used for the separation of the polar and dispersive energy of the different n-alkanes and polar solvents adsorbed on the different PMMA surfaces. The London dispersive surface energy γ_s^d (T) of PMMAs was determined by applying the Hamieh thermal model that took into account the effect of the temperature on the surface area of adsorbed molecules. The obtained results showed non-linear variations of γ_s^d (T) of atactic, isotactic, and syndiotactic PMMAs with three maxima characterizing the three transition temperatures of PMMAs, T_g, T_g and T_(liq-liq) with a shift of these temperatures with the isotactic and syndiotactic PMMAs. It was showed that the polar interaction free energy ∆G_a^p (T) also showed the presence of the three above transition temperatures of the polymers. The study showed an important non-linearity variation of the different acid-base parameters in the various polymer surfaces proving the highest effect of the temperature and the tacticity on these parameters. The determination of the enthalpic and entropic Lewis’s acid-base parameters showed an amphoteric character for the different PMMAs. The basicity of the atactic PMMA was about four times larger than its acidity outside the neighborhood of the transition temperatures of the polymer. Whereas, the isotactic PMMA was about 2 to 2.5 times more basic than acid, while the syndiotactic PMMA exhibited the highest basicity by showing a surface 5 to 8 times more basic than acid. However, the Lewis acid-base parameters strongly depended on the temperature and sudden variations of these surface parameters were observed around the transition temperatures largely depending on the PMMA tacticity. The determination of the polar acid and base surface energies of the three PMMAs led to the same previous transition temperatures with an important effect of the tacticity of PMMA on the values of these acid-base surface energies.

The physical roots, interpretation, controversies and precise meaning of the Landauer Principle are surveyed. Landauer's principle is a physical principle pertaining to the lower theoretical limit of energy consumption of computation. It states that an irreversible change in information stored in a computer, such as merging two computational paths, dissipates a minimum amount of heat kBTln2 per a bit of information to its surrounding. The Landauer Principle is discussed in the context of fundamental physical limiting principles, such as the Abbe diffraction limit, the Margolus-Levitin limit and the Bekenstein limit. Synthesis of the Landauer bound with the Abbe, Margolus-Levitin limit and Bekenstein limits yields the minimal time of computation, which scales as τmin~hkBT. Decrease in a temperature of a thermal bath will decrease the energy consumption of a single computation, but, in parallel, it will slow the computation. The Landauer principle bridges between John Archibald Wheeler “it from bit” paradigm and thermodynamics. Experimental verifications of the Landauer Principle are surveyed. Interrelation between thermodynamic and logical irreversibility is addressed. Generalization of the Landauer principle to the quantum and non-equilibrium systems is addressed. Landauer Principle represents the powerful heuristic principle bridging the physics, information theory and computer engineering.

This study delves into the critical domain of public procurement, specifically focusing on Sustainable Public Procurement (SPP) and Environmental, Social, and Governance (ESG) considerations within the context of South Korea. The aim of this research is to empirically scrutinize the factors influencing the impact index of SPP, with a particular emphasis on services related to labor standards. The investigation spans three years, from January 1, 2019, to July 31, 2021, encompassing state agency orders and post-implementation legal changes. Leveraging the comprehensive Korea On-line E-Procurement Sys-tem(KONEPS) platform, we meticulously collected data, ultimately culminating in 21,573 services meeting our criteria, from which 250 cases underwent an in-depth analysis. The study sheds light on the influence of social responsibility evaluation cri-teria on overall procurement scores, while also uncovering the moderating effects of various factors. The outcomes of this study offer valuable insights into the impact index of social responsibility evaluation criteria within South Korea's public procurement landscape. Factors including procurement year, classification, service period, and estimated price were identified as significant influencers. Moreover, the number and location of evalu-ation criteria items, inclusion of sincerity elements, and the evaluating agency were deemed pivotal determinants of the influence index. These findings hold profound implications for policymakers, procurement practitioners, and researchers and provide a roadmap for optimizing the utilization of social responsibility evaluation criteria to advance responsible and sustainable procurement practices. Future research avenues include conducting further study of additional moderat-ing variables, expanding datasets to encompass a broader spectrum of procurement contexts, and evaluating the long-term repercussions of social responsibility evaluation on procurement outcomes. These endeavors promise to further refine and advance public procurement practices in South Korea and beyond.

The temperature effect plays an important role for an accurate determination of the polar free energy, polar thermodynamic parameters, and enthalpic and entropic Lewis’s acid base properties of oxides, polymers and composites polymers/oxides. The adsorption of polymers on other solid surfaces is crucial in many industrial applications, coatings, paints, catalysis, colloids and adhesion processes. (1) Background: Inverse gas chromatography at infinite was used for the physico-chemical characterization of solid substrates by determining the thermodynamic parameters of adsorption of model organic solvents on solid surfaces such as polymers, metallic oxides, carbon fibers, pharmaceutical or 3D/4D printing substrates. (2) Methods: A new method based on the London dispersion equation was applied with a new parameter associating the deformation po-larizability and the harmonic mean of the ionization energies of solvent. More accurate values of the dispersive and polar interaction energies of the various organic solvents adsorbed on PMMA in bulk phase and PMMA/silica at different recovery fractions were obtained as well as the Lewis acid-base parameters and the transition temperatures of the different composites. (3) Results: This new methodology gave very interesting results on the behavior of PMMA adsorbed on silica. An important effect of the temperature and the recovery fraction on the various physicochemical and thermodynamic properties was highlighted. The variations of all interaction parameters showed the presence of three transition temperatures for the different PMMA adsorbed on silica with the various coverage rates with a shift of these temperatures for a recovery fraction of 31% (4) Con-clusions: An important variation of the polar enthalpy and entropy of adsorption, the Lewis ac-id-base parameters and the intermolecular separation distance as a function of the temperature and the recovery fraction of PMMA on silica.

Developing sustainability competences is an important endeavor for education, as competence development can be complex and requires appropriate approaches. In the case of preparing future educators, this becomes even more important, because of their multiplier role. The current study presents how a project, based on living-lab methodology, helped preservice preschool teachers, attending a course on sustainability issues, develop sustainability-specific professional action competence. Students collaborated with an organization and a school and were trained to deliver to 6-year-old pupils, activities concerning the protection of sea turtles. The process included reflection, based on a given template. After the intervention, the preservice preschool teachers reflected upon their role and professional performance and discussed how they, benefited from this project. They further analyzed through a group interview, how the Living Lab methodology raised their professional confidence and self-efficacy, and helped them develop content knowledge, pedagogical content knowledge, and a sense of purpose and motivation for teaching about sustainability. Outcomes indicate that participants felt confident and efficacious to teach about sustainability, and developed their content knowledge, pedagogy content knowledge, motivation, and volition due to a strong sense of purpose and responsibility. The overall process facilitated the development of critical thinking, systemic thinking, reflection, and collaboration..

This study introduces SkinLiTE, a lightweight supervised contrastive learning model, tailored to enhance the detection and typification of skin lesions in dermoscopic images. The core of SkinLiTE lies in its unique integration of supervised and contrastive learning approaches, which leverages labeled data to learn generalizable representations. This approach is particularly adept at handling the complexities and imbalances inherent in skin lesions datasets. The methodology encompasses a two-phase learning process. In the first phase, SkinLiTE utilizes an encoder network and a projection head to transform and project dermoscopic images into a feature space where contrastive loss is applied, focusing on minimizing intra-class variations while maximizing inter-class differences. The second phase freezes the encoder's weights, leveraging the learned representations for classification through a series of dense and dropout layers. The model was evaluated using three datasets from Skin Cancer ISIC 2019-2020, covering a wide range of skin conditions. SkinLiTE demonstrated superior performance across various metrics—accuracy, AUC , and F1 score—particularly when compared with traditional supervised learning models. Notably, SkinLiTE achieved an accuracy of 0.9087 using AugMix augmentation for binary classification of skin lesions. It also showed comparable results with the state-of-the-art approaches of ISIC challenge without relying on external data, underscoring its efficacy and efficiency. The results highlight the potential of SkinLiTE as a significant step forward in the field of dermatological AI, offering a robust, efficient, and accurate tool for skin lesion detection and classification. Its lightweight architecture and ability to handle imbalanced datasets make it particularly suited for integration into Internet of Medical Things environments, paving the way for enhanced remote patient monitoring and diagnostic capabilities. This research contributes to the evolving landscape of AI in healthcare, demonstrating the impact of innovative learning methodologies in medical image analysis.

We suppose that a Cooper pair (CP) will experience a damping force exerted by the condensed matter. A Langevin equation of a CP in two dimensional condensed matter is established. Following a method similar to Nelson's stochastic mechanics, generalized Schr\"{o}dinger equation of a CP in condensed matter is derived. If the CPs move with a constant velocity, then the corresponding direct current (DC) electrical conductivity can be calculated. Therefore, a Drude like formula of resistivity of CPs is derived. We suppose that the damping coefficient of CPs in two dimensional cuprate superconductors is a linear function of temperature. Then the resistivity and scattering rate of CPs turn out to be also linear-in-temperature. The origin of linear-in-temperature resistivity and Planckian dissipation in cuprate superconductors may be the linear temperature dependence of the damping coefficient of CPs.

The poly lactic acid (PLA) is one of the most used bio-derived thermoplastic polymers in 3D and 4D printing applications. The determination of PLA surface properties is of capital importance in 3D/4D printing technology. (1) Background: The surface thermodynamic properties of PLA polymer were determined by using the inverse gas chromatography (IGC) technique at infinite dilution. The determination of the retention volume of polar and non-polar molecules adsorbed on the PLA particles filling the column allowed us to obtain the dispersive, polar, and Lewis’s acid-base surface properties at different temperatures from 40 °C to 100 °C. (2) Methods: the applied surface method was based on our recent model that used the London dispersion equation and the new chromatographic parameter function of the deformation polarizability and the harmonic mean of the ionization energies of the PLA polymer and organic molecules. (3) Results: The application of this new method led to the determination of the dispersive and polar free surface energy of adsorption of molecules on the polymeric material, as well as the glass transition and the Lewis acid-base constants. (4) Conclusions: four interval temperatures were distinguished showing four zones of the variations of the surface properties of PLA as a function of the temperature before and after the glass transition.

Obesity poses significant challenges in rural communities worldwide due to limited resources and healthcare access. Practical, innovative, and culturally sensitive approaches are essential. Time-Restricted Eating (TRE), aligning food intake with circadian rhythms, emerges as a promising strategy. By restricting eating to specific time windows, TRE synchronizes with the body's internal clock, offering potential metabolic health benefits. This review examines TRE's potential in rural obesity management, highlighting its simplicity and scalability. While TRE may address rural health disparities, cultural considerations and challenges such as undernutrition must be acknowledged for effective implementation. Overall, TRE shows promise in improving metabolic health and well-being in rural populations.

Herbal Coffee is getting more popular due to its unique flavor and higher concentration of bioactive compounds, mainly polyphenols. Rosemary is a unique herb with potent antioxidant properties. A green technique called ultrasound aids in releasing bioactive substances from the plant cell wall. In this context, ultrasound-assisted herbal coffee prepared and their anti-diabetic, anti-Alzheimer, and antioxidant activities were measured while the LC/MS was used to determine the bioactive components from the herbal coffee infusion. A total of 95 secondary metabolites were putatively reported, including alkaloids, phenolic acids, and flavonoids, which we identified in the herbal coffee infusion. The total phenolic content (61.5 ± 5.1 mg GAE/g), total flavonoid content (19.3 ± 0.9 mg QE/g), and total condensed tannin (7.6 ± 0.7 mg CE/g) of herbal coffee infusion were observed to be highest of the two remaining samples. The herbal coffee extracts were used to determine all samples' antioxidant, anti-diabetic, and anti-Alzheimer activities. Using LC-MS/MS, we semi-quantified 19 phenolic metabolites. The results show numerous bioactive components in herbal coffee infusion with more potent antioxidant, antidiabetic, and anti-Alzheimer potential. Moreover, more studies must be conducted to confirm how the metabolomic profile of herbal coffee affects its flavor profile.

Interstitial lung disease (ILD) is one of the most serious extra-articular complications of rheu-matoid arthritis (RA), which increases the mortality of RA. Because the pathogenesis of RA-ILD remains poorly understood, appropriate therapeutic strategies and biomarkers have not yet been identified. Thus, the goal of this review was to summarize and analyze the reported data on the etiology and pathogenesis of RA-ILD. The incidence of RA-ILD increases with age, and is also generally higher in men than in women and in patients with specific genetic variations and eth-nicity. Lifestyle factors associated with an increased risk of RA-ILD include smoking and exposure to pollutants. The presence of an anti-cyclic citrullinated peptide antibody, high RA disease activity, and rheumatoid factor positivity also increase the risk of RA-ILD. We also explored the roles of biological processes (e.g., fibroblast–myofibroblast transition, epithelial–mesenchymal transition, and immunological processes), signaling pathways (e.g., JAK/STAT and PI3K/Akt), and the his-topathology of RA involved in RA-ILD pathogenesis based on published preclinical and clinical models of RA-ILD in animal and human studies.

Concrete contributes 8% of all global carbon emissions making the need to find substitute critical for environmental sustainability. Research has indicated the potential for recycled plastics to be used as concrete substitutes. This study extends existing research by investigating the use of polycarbonate (PC) in plastic sand bricks as a mechanical equivalent to concrete. PC has high compressive strength, durability, impact strength, thermal resistivity, clarity, fatigue resistance, and UV resistance. This work provides a method and mold to produce a matrix of sand-plastic sample compositions with dimensions adhering to ASTM D695 standard for compressive properties of rigid-plastic. Compositions of 0% (control), 20%, 30%, 40%, and 50% sand by weight were tested. Samples were tested for compressive strength until yield and stress-strain behaviors plotted. The results for 100% PC demonstrated an average and maximum compressive strength of 71 MPa and 72 MPa, respectively. The 50% PC and 50% sand composition yielded an average and maximum compressive strength of 71 MPa and 73 MPa respectively with an increase in compressive stiffness, and transition to shear failure resembling cement. With a composite density of 1.86 g/cm3 against concrete’s average 2.4 g/cm3, and a compressive strength exceeding commercial concrete demands of 23.3 MPa to 30.2 MPa, this lightweight alternative meets the strength demands of concrete, reduces the need for new construction materials, and provides an additional recycling opportunity for nonbiodegradable waste plastic.

Proposed fundamental laws of biology and a model of health and disease underscore the importance of the lymphatic system. The lymphatics are responsible for two of the laws of biology and the fulcrum of health and disease balancing proliferation with regeneration through the immune system. It is responsible for protection from the environment and repair of senile and damaged tissue. Life is constantly bombarded by forces that increase entropy. Lymphatics provide negative entropy to maintain health. Lymphatics help maintain cellular homeostasis removing products of metabolism. Using these principles, the role of lymphatics is investigated in salt sensitivity hypertension, cardiorenal system, the new pillar of heart failure and kidney disease - Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors, and brain diseases. The realization of organ lymphatics in maintenance of health and disease opens the avenue to new therapeutics. This is the unrealized potential of lymphatic study.

The objective of this research is to establish a better understanding of the current landscape of digital learning research and sustainable development by using CiteSpace. First, we retrieved published publications from the Web of Science (2004–2022). Following that, we examined the primary research strengths and important subjects of digital learning from two perspectives: collaboration networks (including collaborative networks across countries, institutions, and authors) and co-citation networks. We examined the co-citation network from three perspectives: cluster analysis, the most active citers, top references. Furthermore, referenced journals, popular themes, and rising trends were examined. These findings indicate the primary study subjects in the field of digital learning, the most intriguing research literature, and each period's emerging research hotspots. Finally, we proposed further study ideas for future paths.

In bone tissue engineering, ceramics have been the choice due to their excellent biological properties. But the paradigm changed with the discovery of bioactive glasses (BGs) in 1969 by Larry Hench and co-workers, due to their ability to bond to living tissues through the formation of an interfacial bone-like hydroxyapatite layer when the bioglass was put in contact with biological fluids in vivo. Among a number of tested compositions, the one exhibiting the highest bioactivity index is the well-known trademarked 45S5 Bioglass®. The topic received increasing attention particularly after 1985 when this material entered in the market of biomedical devices, inspiring many other investigations aiming at further exploring the in vitro and in vivo performances of this BG, or developing other related BG compositions. The research efforts gradually revealed a number of shortcomings of 45S5 Bioglass®, mostly derived from its high sodium content, initially intended to decrease the melting temperature and accelerating the degradation of the silicate network over time. But the extensive release of sodium from 45S5 Bioglass® in the biological fluids creates a high pH cytotoxic environment. Other serious drawbacks include a fast degradation rate, and a poor sintering ability, which hinders the reliable fabrication of porous scaffolds. Therefore, sol-gel was regarded as an attractive alternative to prepare alkali-free BG compositions. The process uses inorganic and/or organic precursors, which undergo hydrolysis and condensation at room-temperature, being less costly. When properly conducted, the sol-gel process might result in amorphous structures with all the components intimately mixed at the atomic scale. Moreover, developing new better performing materials for bone tissue engineering is a growing concern, as the ageing of the world’s population leads to lower bone density and osteoporosis. This work describes the sol-gel synthesis of a novel quaternary silicate-based BG with the composition 60 SiO2 – 34 CaO – 4 MgO – 2 P2O5 (mol%) was prepared using acidified distilled water as single solvent. By controlling the kinetics of the hydrolysis and condensation steps, an amorphous glass structure could be obtained. The results of XRD of samples calcined within the temperature range from 600-900 ºC demonstrated that amorphous nature was maintained until 800 ºC, followed by partial crystallization at 900 ºC. The specific surface area, an important factor in osteoconduction, was also evaluated over different temperatures, ranging from 160.6 ± 0.8 m2/g at 600 ºC down to 2.2 ± 0.1 m2/g at 900 ºC, being accompanied consistent changes in average pore size and agreeing pore size distribution. The immersion of the BG particles in simulated body fluid (SBF) led to the formation of an extensive apatite layer on its surface. These overall results indicate the proposed material is very promising for biomedical applications in bone regeneration and tissue engineering.

.With the increasing use of carbon fiber reinforced plastics in various area, carbon fiber composites based on prepregs have attracted attention in industries and academia research. However, prepreg manufacturing processes are costly, and the strength of structures varies depending on the orientation and defects (pores and delamination). For non-contact evaluation of internal defects, we proposed lock-in infrared thermography to investigate orientation angles after a compression test. We also conducted a drop-weight impact test to study the behaviour of the composites after impact according the fibers orientation for composite fabricated using unidirectional carbon fiber prepregs. Using CAI tests, we determined the residual compressive strength and confirmed the damage modes using a thermal camera. The results of the drop weight impact tests show that the specimen laminated at 0° suffered the largest damage because of susceptibility of the resin to impact. In contrast, the specimens oriented in of 0°/90° and +45°/–45° directions transferred more than 90% of the impact energy back to the impactor because of the lamination of fibers in the orthogonal directions. Furthermore, the specimens that underwent complete damage in the impact tests were subjected to the lock-in method and showed internal delamination and cut fibers. With the finite elements analysis, the damage of each ply could be observed. Moreover, the temperature differences in the residual compression tests were not significant.

Semisolid casting can provide excellent castings, but the nature of the pore-forming mechanisms has not been properly clarified. In the current communication, it was suggested that hydrogen precipitated during slurry making might have a decisive role in the formation of both gas and shrinkage porosity. Intensive stirring at the end of the slurry making process may act as a degassing step. Without the intense stirring, structures of primary slurry particles form around the hydrogen pores, strongly affecting pore formation and feeding during the intensification stage.

Infrared thermography has already been proven to be a significant method in non-destructive evaluation since it gives information with immediacy, rapidity and low cost. However, the thorniest issue for wider application of IRT is the quantification. In this work, we proposed a specific depth quantifying technique by employing the Gated Recurrent Units (GRU) in composite material samples via pulsed thermography (PT). Carbon Fiber Reinforced Polymer(CFRP) embedded with flat bottom holes were designed via Finite Element Method (FEM) modeling in order to precisely control the depth and geometrics of the defects. The GRU model automatically quantified the depth of defects presented in the CFRP material. The proposed method evaluated the accuracy and performance of synthetic CFRP data from FEM for defect depth predictions.

In the quest for more sustainable urban landscape development, the concept of ‘green infrastructure’ (GI) has become central in policy documents and as a multifunctional general planning tool. GI is not however a simple and unambiguous solution. While there in policy documents are claims for more and connected GI, actual urban development takes another direction. The densifying imperative is hard to combine with an increased and more connected GI. This paper argues for a critical and diversified approach to the concept of GI, to facilitate its implementation in urban planning and management. While GI most often is seen as a common asset and a public good, the actual land use negotiations and management responsibilities cannot be limited to a public service discourse, but should address more clearly a variety of actors. Linguistic as well as spatial definitions of the two relevant dichotomies of ‘green-grey’ and ‘public-private’ are crucial in GI location, design, construction and management, it is argued. Overarching representations of GI will be needed, but also – and linked to it – a spatial storm water plan and an overall plan for public space. The development over time will need an intersectorial implementation and management program. Thus some of the GI intentions may be implemented in planning processes, some through reorganisation and redesign of public space, and some by agreements with landowners.

Motivated by a common Mathematical Finance topic, this paper surveys several results concerning windings of 2-dimensional processes, including planar Brownian motion, complex-valued Ornstein-Uhlenbeck processes and planar stable processes. In particular, we present Spitzer's asymptotic Theorem for each case. We also relate this study to the pricing of Asian options.

In this data deposit, I describe a dataset that is the result of content mining 167,318 published articles for statistical test results. As a result of this content mining, 688,112 results from 50,845 articles were extracted. In order to provide a comprehensive set of data, the statistical results are supplemented with metadata from the article they originate from. The dataset is provided in a comma separated file (CSV) in long-format. For each of the 688,112 results, 20 variables are included, of which seven are article metadata and 13 pertain to the individual statistical results (e.g., reported and recalculated p-value). A five-pronged approach was taken to generate the dataset: (i) collect journal lists, (ii) spider journal pages for articles, (iii) download articles, (iv) add article metadata, and (v) mine articles for statistical results.

Chronic Hepatitis B Virus (HBV) infection remains a significant public health concern, particularly in Africa, where the burden is substantial. HBV is an enveloped virus, classified into ten phylogenetically distinct genotypes (A – J). Tests to determine HBV genotypes are based on full-genome sequencing or reverse hybridization. In practice, both approaches have limitations. Whereas diagnostic sequencing, generally using the Sanger approach, tends to focus only on the S-gene and yields little or no information on intra-patient HBV genetic diversity, reverse hybridization detects only known genotype-specific mutations. To resolve these limitations, we developed an Oxford Nanopore Technology (ONT)-based HBV diagnostic sequencing protocol suitable for clinical virology that yields both complete genome sequences and extensive intra-patient HBV diversity data. Specifically, the protocol involves tiling-based PCR amplification of HBV sequences, library preparation using the ONT Rapid Barcoding Kit, ONT GridION sequencing, genotyping using Genome Detective software, recombination analysis using jpHMM and RDP5 software, and drug resistance profiling using Geno2pheno software. We prove the utility of our protocol by efficiently generating and characterizing high-quality near full-length HBV genomes from 148 residual diagnostic samples from HBV-infected patients in the Western Cape province of South Africa, providing valuable insights into the genetic diversity and epidemiology of HBV in this region of the world.

Background/Objectives: Distance or urbanisation settings may affect active commuting to school (ACS). This study aimed to (i) detect home-school threshold distances of walking to school and (ii) predict walkable distances among adolescents in different urbanisation settings and both sexes, and (iii) to identify variables predicting adolescents’ ACS, in a central Spain region. Methods: The PACOyPACA (Spanish acronym for Pedal-and-Walk to School, Pedal-and-Walk Home) study evaluated adolescents attending urban, semi-urban and rural schools from Castilla-La Mancha region. The sample included 448 adolescents [48.9% females, mean age 14.80 (SD=0.60)] living closer than 5,100m from school. Distance was divided into deciles to detect which adolescents walked more. Most walkable distances within the whole sample, by sex and by urbanisation settings were predicted using Receiver Operating Characteristic (ROC) curves. Variables affecting ACS were found with binary logistic regression. Significance was set at p≤0.05. Results: Most adolescents walked to school (73.1%). Commuting modes differed significantly by urbanisation settings (p=0.001), but not by sex. Most walked when living around 1,400m from school or closer within the whole sample, in both sexes and in urban and semi-urban settings, and adolescents within rural settings did it until 750-900m. Walkable distances were 1,350m for the whole sample and both sexes, and 1,450, 1,350 and 800 within urban, semi-urban and rural settings, respectively. Distance was the only predictor of ACS (p&lt;0.001). Conclusions: Walkable home-school distances differed based on urbanisation settings, which may be due to the classification of urbanisation settings. This study addresses schools within scarcely populated areas.

Primary themes in intergenerational justice are a healthy environment, the perpetuation of Earth’s biodiversity, and the sustainable management of the biosphere. However, the current rate of species declines globally, ecosystem collapses driven by accelerating and catastrophic global heating and a plethora of other threats, preclude the ability of habitat protection alone to prevent a cascade of amphibian and other species mass extinctions. Reproduction biotechnologies, biobanking, and conservation breeding programs (RBCs), enabling species restoration, offer a critical transformative change that can economically and reliably perpetuate species irrespective of environmental targets. These capacities extend indefinitely into the future and satisfy humanities needs as the biosphere expands into space. Currently applied RBCs include the hormonal stimulation of reproduction, the collection and refrigerated storage of sperm and oocytes, sperm cryopreservation, in vitro fertilisation, along biobanking. Advanced biotechnologies such as assisted evolution and cloning for species adaptation or restoration have yet to be fully realised. We broaden our discussion to include genetic management, broad political and cultural engagement, and future applications. The development and application of RBCs, and particularly assisted evolution and species restoration, raise intriguing ethical, theological, and philosophical issues. We address these themes with amphibian models to introduce the MDPI Special Issue, The Sixth Mass Extinction and Species Sustainability through Reproduction Biotechnologies, Biobanking, and Conservation Breeding Programs.

Clostridioides difficile is a Gram-positive pathogen known for its toxin production and spore formation. It is primarily responsible for most cases of antibiotic-associated diarrhea. Bacterial persisters are a small subset of the population that exhibits transient tolerance to bactericidal substances, and they are of significant medical concern due to their association with the emergence of antibiotic resistance and difficult-to-treat chronic or recurrent infections. Vancomycin, the predominant antibiotic utilized in the management of C. difficile infection, is extensively applied in the realm of clinical practice. Previous studies have demonstrated a persister-like phenotype with treatments involving this antibiotic. However, the mechanism in C. difficile remains largely unknown, primarily due to the challenge of isolating this small population at any given time. To better characterize C. difficile persister cells, we present a study that enables the enrichment and characterization of persister cells from bacterial cultures in both exponential and stationary phases. Moreover, we could differentiate between triggered (induced by antibiotics, such as vancomycin) and spontaneous (stochastic) persister cells. Additionally, we observed the involvement of toxin-antitoxin systems and Clp proteases in persister cell formation.

Objective: To analyse the association between maternal risk factors such as age, body mass index (BMI) and cigarette smoking, with perinatal outcomes. Materials and Methods: This a retrospective analysis from prospectively collected data performed at Hospital Universitario de Torrejón (Madrid, Spain), between September 2017 and December 2019. All pregnant women with singleton pregnancies and non-malformed live fetuses attending their routine ultrasound examination at 11+0 to 13+6 weeks' gestation were invited to participate. Association between preeclampsia, preterm birth, gestational diabetes mellitus (GDM), small for gestational age (SGA) or fetal growth restricted (FGR) neonates and type of delivery according to maternal age, BMI, and cigarrete smoking was studied. Logistic mixed models were used to analyze the data. Results: 1921 patients were included in the analysis. Women of 40 years old had a significantly higher risk of having GDM (Odds Ratio (OR) 1.61, 95% Confidence Interval (CI) 1.08 to 2.36), and SGA neonates (OR 1.54, 95% CI 1.00 to 2.37). Women with a BMI &lt;18 had an increased rate of birth SGA and FGR neonates (OR 3.28, 95% CI 1.51 to 7.05, and OR 3.73, 95% CI 1.54 to 8.37, respectively), whereas women with a BMI ≥35 had a higher risk of GDM (OR 3.10, 95% CI 1.95 to 4.89). Smoking increased the risk of having SGA and FGR neonates (OR 1.83, 95% CI 1.36 to 2.46, and OR 1.91, 95% CI 1.29 to 2.78). Conclusions: Advanced maternal age, low or high BMI, and smoking status are significant risk factors for pregnancy complications. Both clinicians and society should concentrate their efforts on addressing these factors to enhance reproductive health.

Cytomegalovirus (CMV) is the leading infectious cause of brain defects and neurological dysfunctions, including sensorineural hearing loss (SNHL). A targeted screening in neonates failing the hearing screen is currently recommended in Italy according to national guidelines. However, SNHL may not be present at birth; also, congenital CMV (cCMV) may manifest with subtle signs other than SNHL. Therefore, inclusion of additional criteria for cCMV screening appears clinically valuable. Starting January 2021, we have implemented an expanded targeted cCMV screening at our center, with testing in case of maternal CMV infection during pregnancy, inadequate antenatal care, maternal HIV infection or immunosuppression, birthweight and/or head circumference.

Alzheimer's disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords GB in AD and dementia yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show Ginkgo biloba has promising potential in these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a specific subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1's mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was safe and well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is safe and well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest.

The present study aimed at investigating the in vitro and in vivo susceptibility of malaria parasites to crude extracts and fractions from Polyalthia suaveolens, Uvaria angolensis, and Monodora tenuifolia. The ethanolic extracts were prepared by maceration, and were further partitioned using water, dichloromethane, hexane, and methanol. The most promising fraction was subjected to column chromatography and the sub-fractions tested for activity in vitro. The antiplasmodial effect of extracts and fractions was tested against the Chloroquine resistant (PfK1) strain in 96 wells microtiter plate format using SYBR green florescence assay. The promising fraction was further assessed for cytotoxicity and acute toxicity in Swiss albino mice and subsequently against the rodent malaria parasite, P. berghei. Qualitative phytochemical screening was also performed on the promising fraction. The methanol fractions exerted the overall better effect with that of the twigs of P. suaveolens (PStw(Ace)) showing the highest potency with a IC50 value of 3.24 µg/mL followed by the fractions of leaf of M. tenuifolia (MoTel(Ace), IC50= 3.84 µg/ml) and stem bark of P. suaveolens (IC50= 4.90 µg/ml). The phytochemical screening showed the presence of alkaloids, lactones, and phenols in the more active fraction of P. suaveolens (PStw(Ace)). The chromatographic fractionation of this fraction led to 12 sub-fractions with PS8 sub-fraction being the most active (IC50= 4.42 µg/mL). In vivo, oral administration of 2000 mg/kg b.w of fraction PStw(Ace) in mice showed no signs of toxicity. Also, fraction PStw(Ace) at 400 mg/kg b.w exerted the highest suppressive effect against P. berghei strain B throughout the 4 days experiment (% parasitaemia below 5.2%). Overall, the results achieved supported the use of the three plants in the traditional treatment of malaria in Cameroon. More interestingly, the methanolic fraction of the twigs extract from P. suaveolens might be of interest in future development of an antimalarial phytodrug.

Cationic Antimicrobial Peptides (AMPs), also called Host Defence Peptides have established antimicrobial and anticancer activities. Conjugation of an AMP to a bioactive molecule with complementary activity can address some of the clinical limitations of the peptide candidate. This approach has been particularly applied in antimicrobial applications of AMPs, but remains relatively less explored in the generation of anticancer candidates. Herein, two usnic acid derivatives, based on hydrazinothiazole and benzylidenefuranone pharmacophore moieties, respectively, have been conjugated to L-K6, a lysine/leucine rich AMP, through a new pyrazole ligation intrinsically driven by the cargo molecule. Both components, the usnic acid derivative and the peptide, are selectively active against cancer cells, by targeting the human DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) and through DNA damage, respectively. The two conjugates, based on a hydrazone linkage, exhibited pleiotropic effects, ranging from, overall, reduction of the activity from the parent drugs to their conservation or even enhancement. Notably, the conjugates retain some anti-TDP1 activity and display intermediate, or even higher, cytotoxicities against glioblastoma cells, compared to their individual components.

Background and objectives: Chronic Kidney Disease and Mineral Bone Disorders (CKD-MBD) are frequently associated with an increased risk of both Vascular Calcifications (VCs) and bone fractures (BFs). The complex pathogenesis of VCs and BFs involves various factors such as calcium overload, phosphate imbalance, and secondary hyperparathyroidism. Key players, such as the vitamin K-dependent proteins (VKDPs) matrix Gla protein (MGP) and osteocalcin (BGP), have pivotal roles both for VCs and BFs. The Vitamin K Italian (VIKI) dialysis study, highlighted that hemodialysis patients treated with calcimimetics had higher levels of total BGP and MGP as compared to those untreated, suggesting a potential protective effect of these drugs on BFs and VCs, beyond the beneficial effect to reduce PTH levels. Methods: ETERNITY-ITA is a multi-center, comparative effectiveness, observational, longitudinal study that will enroll 160 hemodialysis patients (80 patients treated with Etelcalcetide and 80 age and sex-matched patients treated with Calcitriol or vitamin D analogs). Nephrologists will tailor the target dose of Etelcalcetide on individual level to achieve the KDIGO PTH target. In the Etelcalcetide-treated group, the addition of calcitriol will be allowed when required by clinical practice (for correction of hypocalcemia). Conclusion: The study will evaluate the real-world effect of Etelcalcetide on VKDP levels, such as BGP and MGP, at 3, 9, and 18 months from baseline. The resulting preservation of vascular and bone health will be assessed for the first time by examining aortic and iliac artery calcifications and vertebral fractures, respectively. Keywords: bone fractures; etecalcetide; hemodialysis; vascular calcification; vitamin K

Sarcoglycanopathies are among the most frequent and severe autosomal recessive forms of limb-girdle muscular dystrophies /LGMD/ with childhood onset. Mutations in , , and sarcoglycan genes lead to various kinds of LGMD. We present the clinical variability of LGMD 2C/R5 among a genetically homogeneous group of 56 patients, belonging to 35 pedigrees. Molecular genetic analysis showed thаt all 57 patients were homozygous for C283Y variant. The muscles of the pelvic girdle and the trunk were early and more severely affected, followed by the the shoulder girdle. Macroglossia, hypertrophy of the calves, scapular winging and lumbar hyperlordosis were common in the ambulatory phase. A great variability in the clinical presentation of LGMD 2C/R5 was observed both intra and interfamilial, despite the same underlying molecular defect. Females demonstrated a relatively milder clinical course, compared to males. Mean CK levels were 20 times above normal values. Muscle CT of MRI showed earlier and more severe involvement of the flexor proximal limb muscles in comparison to the extensor ones.

Vascular impairment, muscle atrophy, and cognitive decline are important age-related conditions that have a significant impact on health. Vascular impairment directly disrupts the flow of blood, leading to the decline of muscle mass associated with aging (sarcopenia) and the decline of neuronal functions (neurodegeneration). Our inadequate understanding of the complex relationships between these conditions impedes precise diagnosis and effective treatment. This review analyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on oxidative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sarcopenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, inflammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can enhance therapeutic strategies and lead to better outcomes for patients. Here, we highlight the intricate relationship among vascular dysfunction, degenerative muscle, and cognitive decline, underscoring the need for multidisciplinary approaches to treatment. Progress in this field can result in improved diagnosis, more potent therapeutic options, and enhanced preventative measures, all of which can contribute to an improved quality of life for the aging population.

In the pursuit of functional foods that promote health, nanoliposomal carriers have been used to enhance the stability and functionality of dairy products such as yogurt, promising therapeutic benefits. This study aimed to evaluate the impact of fucoxanthin-loaded nanoliposomes in yogurt on its antioxidant, physico-chemical, and rheological properties under cold storage (21 days). Fucoxanthin-loaded nanoliposomes were prepared using the ultrasonic film dispersion technique and added at concentrations of 0%, 5% and 10% at the yogurt (Y-C, Y-FXN-5, Y-FXN-10). Homogeneous and uniform nanoliposomes (98.28 nm) were ob-tained, preserving their integrity and functionality, and ensuring prolonged release and bioavailability of fucoxanthin. Y-FXN-10 maintained the highest antioxidant activity according to the DPPH (52.96%), ABTS (97.97%), and FRAP (3.16 mmol ET/g) methods. This formulation exhibited enhanced erythroprotective potential, inhibiting hemolysis, photohemolysis, and heat-induced hemolysis, thereby preventing lipid pe-roxidation. However, viscosity and firmness decreased, affecting the texture and appearance. Sensory properties such as color, flavor, aftertaste, texture, and overall acceptance improved with the 10% fuco-xanthin-enriched yogurt formulation. These results suggest that nanoliposomal are suitable for carries fuco-xanthin, their incorporation into food matrices is key to developing functional foods. Regulatory approvals and consumer perceptions regarding nanotechnology-based products must be addressed, emphasizing their safety and health benefits.

Background: Preserving health and physical fitness is critical to ensure independent living across the lifespan. Lower levels of physical fitness are associated with age-related cognitive decline and a higher prevalence of mild cognitive impairment (MCI). Thus, this study investigates the influence of a six-month dance intervention on selected measures of physical fitness in older adults with MCI. Methods: In this randomized controlled trial 55 patients with MCI were randomized into a sportive dance training (IG; n=26; Age: 70.7 +/- 5.6 years; 62% female) or an inactive control group (CG; n=24; Age: 69.1 +/- 6.8 years; 46% female).The dance group received two 90-minute dance training sessions per week over a duration of six-months, which focused on learning dance movement patterns. During the training sessions, heartrate was measured to control exercise intensity. Physical fitness was assessed using cardiopulmonary exercise testing (CPET), lower limb functional fitness via sit-to-stand test, handgrip strength and heart rate variability (HRV). Results: We observed that the dance intervention preserved the cardiorespiratory fitness as measured by maximal oxygen uptake (VO2max) during CPET, which decreased in the CG. Furthermore, participants in the IG demonstrated increases in leg and handgrip strength although not statistically significant. HRV displayed a nonsignificant decrease following the intervention. Conclusion: The results of this randomized controlled trial suggest that sportive dance training can preserve physical fitness in older adults with MCI. Although improvements in the other parameters were statistically non-significant, likely due to the small sample size, stabilizing muscular fitness and preventing age-related decline in older adults with MCI is important for maintaining functional independence.

Our study aimed to identify predictors for the effectiveness of tumor regression in lung cancer patients undergoing neoadjuvant treatment and cancer resections. Patients admitted between 2016 and 2022 were included in the study. Based on the histology of the tumor, patients were categorized into lung adenocarcinoma group (LUAD), and squamous cell carcinoma group (SQCA). Ninety-five patients with non-small cell lung cancer were included in the study. Fifty-eight (61.1%) and 37 (38.9%) patients were included in the LUAD and SQCA groups, respectively. Nine (9.5%), 56 (58.9%), and 30 (31.6%) patients were categorized with a tumor regression score of I, II, and III respectively. In multivariable analyses, histology of the primary tumor (SQCA), lymph node size in the preoperative CT scan (>1.7cm) and absolute tumor size reduction after neoadjuvant treatment (>2.6 cm) independently predict effectiveness of tumor regression (OR, [95% Confidence interval, p-value] of 6.88 [2.40-19.77, p70 years, extended resection >one lobe, and tumor recurrence or metastasis were identified as significant independent predictors of reduced overall survival. Assessment of tumor size before and after neoadjuvant treatment might help to identify high-risk patients with decreased survival and to improve patient management and care.

Background: The incidence of metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC) is increasing annually with a rise in the incidence of obesity and metabolic syndrome. Based on preliminary reports regarding the potential association of HCC and periodontitis, this study aimed to analyze the involvement of periodontal bacteria as well as the oral and intestinal bacterial flora in MASH-related HCC (MASH-HCC). Methods: Forty-one patients with MASH and 19 with MASH-HCC who completed survey questionnaires, underwent periodontal examinations, and subjected to sample collection (saliva, mouth-rinsed water, feces, and peripheral blood) participated in the study. Bayesian network analysis was used to analyze the causation between various factors, including MASH-HCC, examinations, and bacteria. Results: The occupancy rate of the genus Fusobacterium in the intestinal bacterial flora was significantly higher in in the MASH-HCC group than in the MASH group (p = 0.002), whereas that of Butyricicoccus (p = 0.022) and Roseburia (p &lt; 0.05) was significantly lower. Bayesian network analysis revealed the absence of periodontal pathogenic bacteria and enteric bacteria affecting HCC. However, HCC directly affected the periodontal bacterial species Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in the saliva, as well as the genera Lactobacillus, Roseburia, Fusobacterium, Prevotella, Clostridium, Ruminococcus, Trabulsiella, and SMB53 in the intestine. Furthermore, P. gingivalis in the oral cavity directly affected the genera Lactobacillus and Streptococcus in the intestine. Conclusion: MASH-HCC directly affects periodontal pathogenic and intestinal bacteria, and P. gingivalis may affect the intestinal bacteria associated with gastrointestinal cancer.

The mystery phenomenon of fungal bioluminescence has always captivated human curiosity, although more attempts need to be made, particularly to bring the new species to the surface. In this study, we devoted considerable space to the taxonomy of these fungi while discussing their biogeography, evolution, bioluminescence mechanism, and potential ecological roles. We provide a detailed explanation of how these fungi produce light, including the role of the enzyme luciferase and luciferin. We also discussed their applications. Here, we presented an updated list of 122 bioluminescent fungi identified from five distinct evolutionary lineages viz. Armillaria, Eoscyphella, Lucentipes, Mycenoid, and Omphalotus worldwide, mainly in tropical and subtropical areas. The bioluminescent fungi descended from the last common ancestor of the mycenoid and the marasmioid clades of Agaricales, which have been maintained for at least 160 million years of evolution. We highlighted the need for further research to understand the ecological role of bioluminescent fungi. Applying bioluminescent fungi in various areas (e.g., environmental and medicinal) demonstrates their validity.

Approximately 30% of steroid-resistant nephrotic syndromes are attributed to monogenic disorders that involve 27 genes. Mutations in KANK family members have also been linked to nephrotic syndrome; however, the precise mechanism remains elusive. To investigate this, podocyte-specific Kank1 knockout mice were generated to examine phenotypic changes. In the initial assessment under normal conditions, Kank1 knockout mice showed no significant differences in the urinary albumin-creatinine ratio, blood urea nitrogen, serum creatinine levels, or histological features compared to controls. However, following kidney injury with adriamycin, podocyte-specific Kank1 knockout mice exhibited a significantly higher albumin-creatinine ratio and a significantly greater sclerotic index than control mice. Electron microscopy revealed more extensive foot process effacement in the knockout mice than in control mice. In addition, KANK1-deficient human podocytes showed increased detachment and apoptosis following adriamycin exposure. These findings suggest that KANK1 may play a protective role in mitigating podocyte damage under pathological conditions.

World Health Organization recommends adjusting the salt intake as a part of the nine global targets to reduce premature mortality from non-communicable chronic diseases as priority and most cost-effective intervention. In 2006. the main aim of the Croatian Action on Salt and Health was to decrease salt intake for 16% because of its critical intake and consequences on human health. We have organized educative activities for increasing awareness on salt harmfulness, defined food categories of prime interest, collaborate with industries and determine salt intake (24h urine-sodium excretion). It was determined that the proportion of salt in ready-to-eat baked bread should not exceed 1.4%. In the period 2014 –2022, salt in the semi-white bread was reduced 14%, in bakery 22% and in largest meat industry in Croatia 25%. Awareness of the harmfulness of salt on health increased from 65.3% in 2008 to 96.9% in 2023 and salt intake was reduced 15.9%-1.8 grams/day (22.8% men, 11.7% women). In last 18 years a significant decrease in salt intake was achieved in Croatia, awareness of its harmfulness increased, collaboration with food industry established and regulatory documents launched. However, salt intake is still very high underlying the need for continuation of efforts and even stronger activities.

Background/Objectives: Concurrent opioid (OPI) and benzodiazepine (BZD) use may exacerbate falls/fractures risk compared to no use or use alone. Yet, patients may need concurrent OPI-BZD use for co-occurring conditions (e.g., pain and anxiety). Therefore, we examined the association between longitudinal OPI-BZD dosing patterns and subsequent injurious falls risk. Methods: We conducted a retrospective cohort study including non-cancer fee-for-service Medicare beneficiaries initiating OPI and/or BZD in 2016-2018. We identified OPI-BZD use patterns during the 3 months following OPI and/or BZD initiation (i.e., trajectory period) using group-based multi-trajectory models. We estimated time to first injurious fall within 3 months post-trajectory period using inverse-probability-of-treatment-weighted Cox proportional hazards models. Results: Among 622,588 beneficiaries (age≥65=84.6%, female=58.1%, White=82.7%; having injurious falls=0.45%), we identified 13 distinct OPI-BZD trajectories: Group(A):Very-low OPI-only (early discontinuation)(44.9% of the cohort); (B):Low OPI-only (rapid decline)(15.1%); (C):Very-low OPI-only (late discontinuation)(7.7%); (D):Low OPI-only (gradual decline)(4.0%); (E):Moderate OPI-only (rapid decline)(2.3%); (F):Very-low BZD-only (late discontinuation)(11.5%); (G):Low BZD-only (rapid decline)(4.5%); (H):Low BZD-only (stable) (3.1%); (I):Moderate BZD-only (gradual decline)(2.1%); (J):Very-low OPI (rapid decline)/Very-low BZD (late discontinuation)(2.9%); (K):Very-low OPI (rapid decline)/Very-low BZD (increasing)(0.9%); (L):Very-low OPI (stable)/Low BZD (stable)(0.6%); and (M):Low OPI (gradual decline)/Low BZD (gradual decline)(0.6%). Compared with Group(A), 6 trajectories had increased 3-month injurious fall risks: (C): HR, 95%CI=1.78, 1.58-2.01; (D): 2.24, 1.93-2.59; (E): 2.60, 2.18-3.09; (H): 2.02, 1.70-2.40; (L): 2.73, 1.98-3.76; and (M): 1.96, 1.32-2.91. Conclusions: Our findings suggest that 3-month injurious fall risk varied across OPI-BZD trajectories, highlighting the importance of considering both dose and duration when assessing fall risks of OPI-BZD use among older adults.

Opuntia ficus-indica (L.) Mill. belongs to the Cactaceae family and the genus Opuntia; it is a succulent plant that adapts to extreme climatic conditions. The aerial part of the plant consists of the cladodes, morphological changes of branches that appear green, are covered with thorns, and are essential to reduce excessive perspiration of water. The composition of cladodes is very varied, and the main constituents are water, fibers, polysaccharides, proteins, fatty acids, vitamins, sterols, minerals, and polyphenols. Polyphenols are responsible for many beneficial activities for human health, such as antioxidant, anti-inflammatory, antitumor, and nutritional properties. The purpose of this manuscript was to compare the properties of cladodes belonging to the same plant but with different stages of maturity. Relative extracts were tested both in vitro and on a cell line and antioxidant and anti-apoptotic properties were found. The antioxidant activity was tested by the ORAC test, the DPPH test, and the measurement of cellular accumulation of ROS. Anti-apoptotic activity was evaluated by the annexin/PI assay and measurement of caspases 9 and 3 expression. The results obtained have shown that the extracts considered possess antioxidant and anti-apoptotic properties. However, the different stages of maturity of cladodes are essential for the performance of both functions. In addition, important variations have been made in the dissolution of extracts that have brought greater safety in their use. In conclusion, this manuscript provides further information on cladodes of Opuntia ficus-indica, which can be used as adjuvants in many human pathologies.

Hypofunction of the glutamate system in the brain is one of the pathophysiological hypotheses for schizophrenia. Accumulating animal and clinical studies show that sarcosine (N-methylglycine), a glycine transporter-1 inhibitor, is effective for ameliorating the negative and cognitive symptoms of schizophrenia. The aims of the present study were to observe the effects of sarcosine on neuronal activity in the dorsal CA1 (dCA1) hippocampal neurons within an NMDA receptor hypofunction model induced by MK801. We applied in vivo calcium imaging to observe the dynamics of fluorescence from the dCA1 hippocampal neurons when the mice were exploring in an open field. Using this tool, we directly measured and compared neuronal properties between sarcosine-treated and untreated mice. At the same time, the physiological function of the neurons was also quantified by measuring their place fields. Our data demonstrated that MK-801 (0.2 mg/kg) diminished the fluorescence intensity of dCA1 neurons that had been genetically modified with a calcium indicator. MK-801 also significantly increased the correlation coefficient between the fluorescence dynamics of pairs of cells, a feature that may be linked to the symptom of disorganization in human patients with schizophrenia. The spatial correlations of place fields in the mice were impaired by MK-801 as well. Injected sarcosine (500 mg or 1000 mg/kg) significantly alleviated the abovementioned abnormalities. Our data provide evidence to support the use of sarcosine to alleviate symptoms of schizophrenia, especially hippocampus-related functions.

Limited evidence on hepatitis A seroprevalence among HIV-exposed uninfected (HEU) children compared to their HIV infected (HIV) and unexposed uninfected (HUU) counterparts compromises rational vaccine decision-making. This study comprised of a retrospective health facility-based population of children aged 1 month – 12 years. Archival sera were tested for markers of acute (anti-HAV IgM) or past (total anti-HAV) HAV infection. Subgroup analysis was conducted based on HIV exposure or infection status. Of 513 participants, 54% (277) were male and the median age was 10 (IQR: 4 – 25) months. The median maternal age was 29 (IQR: 25 – 34) years. An anti-HAV seropositivity of 95.1% (117/122 [95% CI 90.2-98.4]) was found among those ≤6 months of age, indicative of the rate of transplacental antibody transfer. Among 1–12-year-olds, hepatitis A seroprevalence was 19.3% (37/192 [95% CI 14.1-25.7]), while 1.1% (2/188 [95% CI 0.12-2.76]) had evidence of acute infection. Compared to HIV-exposed subgroups (HIV=60%, 6/10 [95% CI 27.4-86.3] and HEU=45%, 9/20 [95% CI 23.8-68]), hepatitis A seroprevalence among HUU children was low (29.2%, 47/161 [95% CI 22.4-37.0]). Natural immunity among HIV -exposed and -unexposed children in South Africa is insufficient to protect against severe liver complications associated with HAV infection later in adulthood.

The global aging population has experienced rapid growth in recent decades, leading to an increased prevalence of psychiatric disorders, particularly depression, among older adults. Depression in the elderly is often compounded by chronic physical conditions and various psychosocial factors, significantly impacting their quality of life. This paper explores the epidemiology of geriatric depression, highlighting the influence of gender, race, and socio-economic status on its prevalence. The classification and diagnosis of geriatric depressive disorders, based on ICD-11 and DSM-5 criteria, reveal the complexity of managing these conditions in older adults. Personalized Medicine (PM) emerges as a promising approach, focusing on tailoring treatments to the individual’s genetic, clinical, and environmental characteristics. However, the application of PM in this demographic faces challenges, particularly in the context of pharmaceutical forms. The need for age-appropriate drug delivery systems is critical, given the prevalence of polypharmacy and issues such as dysphagia among the elderly. This study emphasizes the importance of developing patient-centric formulations to enhance the effectiveness of personalized therapy in geriatric patients.

Salmonella species are important foodborne pathogens worldwide. Salmonella pathogenicity is associated with multiple virulence factors and enhanced antimicrobial resistance. To determine the molecular characteristics and genetic correlations of Salmonella, 24 strains of Salmonella isolated from different sources (raw poultry, human stool, and food) in the Wenzhou area were investigated to determine the distribution of antimicrobial resistance and virulence determinants using whole-genome sequencing (WGS). Aminoglycoside-resistance genes were detected in all samples. Over half of the samples found antimicrobial resistance genes (ARGs) and point mutations for several clinically frequently used antibiotic, β-lactamases, tetracyclines, and fluoroquinolones. Of these strains, 62.5% were predicted to be multidrug-resistant (MDR). The quinolone-modifying enzyme gene aac(6')-Ib-cr, detected in five samples (S1–S4 and S10), were located on integrons. Analysis of Salmonella pathogenicity island (SPI) profiles suggests that serotypes with close genetic relationships share the same distribution of virulence factors, revealing a link between genotype and SPI profiles. CgMLST analysis indicated that five isolates S14–S18 were closely related to strains originating from the UK, suggesting that they may have been introduced from the UK. Data from this study may enrich the molecular traceability database for Salmonella and provide a basis for effective public health policies.

Clathrate hydrate-based technologies have been considered as promising and sustainable alternatives for the effective management of the climate change risks related to emissions of carbon dioxide, produced by human activities. This work presents a combined experimental and computational investigation of the effects of the operational procedures and characteristics of the experimental configuration, on the phase diagrams of CO2-H2O systems and CO2 hydrates formation, growth and dissociation conditions. The operational modes involved (i) the incremental (step-wise) temperature cycling and (ii) the continuous temperature cycling processes, in the framework of an isochoric pressure search method. Also, two different high pressure PVT configurations were used, of which one encompassed a stirred tank reactor and the other incorporated an autoclave of constant volume with magnetic agitation. The experimental results implied a dependence of the subcooling, (P, T) conditions for hydrate formation and dissociation and thermal stability of the hydrate phase on the applied temperature cycling mode, and the technical features of the utilized PVT configuration. The experimental findings were complemented by a thermodynamic simulation model and other calculation approaches, with the aim to resolve the phase diagrams including the CO2 dissolution over the entire range of the applied (P, T) conditions.

Due to global climate change, cold temperatures have significantly impacted rice production, resulting in reduced yield and quality. In this study, we investigated two traits related to cold tolerance (CT) of 1992 diverse rice accessions at the seedling stage. Geng accessions exhibited higher levels of CT compared to xian accessions, with the GJ-tmp subgroup displaying the strongest CT. However, extreme CT accessions were also identified within the xian subspecies. Through GWAS analysis based on survival rate (SR) and leaf score of cold tolerance (SCT), a total of 30 QTLs associated with CT at the seedling stage were identified, among which four QTLs (qSR3.1a, qSR4.1a, qSR11.1x and qSR12.1a) were found to be important. Furthermore, five candidate genes (LOC_Os03g44760, LOC_Os04g06900, LOC_Os04g07260, LOC_Os11g40610 and LOC_Os12g10710) along with their favorable haplotypes were identified through gene function annotation and haplotype analysis. Pyramiding multiple favorable haplotypes resulted in a significant improvement in CT performance. Subsequently, three selected accessions (CX534, B236, and IRIS_313-8565), carrying different superior alleles for CT, were selected and recommended for molecular breeding for CT using marker-assisted selection (MAS). The findings from this study provide valuable resources for enhancing rice's ability for CT while laying a foundation for future cloning of novel genes involved in conferring CT.

Equine herpesvirus type 1 (EHV-1) causes rhinopneumonitis, abortion and neurological outbreaks (equine herpesvirus myeloencephalopathy, EHM) in horses. EHV-1 also causes lethal encephalitis in laboratory small animals such as mice and hamsters experimentally. EHV-1 ORF76 is a homologue of HSV-1 US9, which is a herpesvirus kinase. Starting with an EHV-1 bacterial artificial chromosome clone of neuropathogenic strain Ab4p (pAb4p BAC), we constructed an ORF76 deletion mutant (Ab4p∆ORF76) by replacing ORF76 with the rpsLneo gene. Deletion of ORF76 had no influence on replication, cell-to-cell spread in cultured cells or replication in primary neuronal cells. In western blots of EHV-1-infected cell lysates, an EHV-1 Us9-specific polyclonal antibody detected multiple bands ranging from 35 to 42-kDa. In a CBA/N1 mouse infection model following intranasal inoculation, the parent and Ab4p∆ORF76 revertant caused the same histopathology in the brain and olfactory bulbs. The parent, Ab4p∆ORF76 and revertant mutant replicated similarly in the olfactory mucosa, although Ab4p∆ORF76 was not transported to the olfactory bulbs and was unable to infect the CNS. These results indicated that the ORF76 (US9) plays an essential role in the anterograde spread EHV-1.

Increasing awareness of the potential health risks associated with microplastics (MPs) presence in the environment has led to significant rise in research focused on these particles over the past few years. This review focuses on research on MPs presence and spread, pathways of exposure and toxicological effects on human health and legal framework related to MP challenges. Several research projects have aimed to assess their potential harm to human health. Toxicological effects have been noticed at high concentrations of MPs, specifically polystyrene, the most widespread typical MP, but only short-term effects have been mostly studied. Significant quantities of consumed MP have been discovered to have diverse detrimental effects, posing a threat to human welfare. The exact concentrations of microplastics that are inhaled and swallowed and then build up in the human body are still not known. Further investigation is necessary to evaluate the impact of MP contamination at minimal concentrations and for prolonged durations.

Background: Ventilatory strategies in acute respiratory distress syndrome patients aim to mitigate the risk of acute lung injury (ALI). However, prolonged utilization of these strategies may precipitate alveolar carbon dioxide elevation and pH reduction. This scoping review endeavors to present extant knowledge concerning hypercapnia effects in experimental models, with or without ALI, specifically focusing on delineating the immunologically mediated pulmonary tissue damage; Methods: A systematic exploration encompassing PubMed, Web of Science, ScienceDirect, Cochrane Reviews, and Scielo databases was undertaken. Articles published between January 1, 2008, and December 31, 2022, were screened for their elucidation of hypercapnia's immunological impact on lung tissue, utilizing experimental or biological models, irrespective of ALI presence; Results: Following duplicate removal and predefined criteria filtering, 30 pertinent articles scrutinizing hypercapnia's influence on pulmonary epithelium were identified. It was observed that hypercapnia induces perturbations in innate immune response gene transcription, mediated via Nuclear Factor-kappa B attenuation. Furthermore, a compromised innate immune response against injurious agents was noted. Concurrently, disruption and subsequent resealing of alveolar epithelial cells were evidenced, primarily through Na/K-ATPase endocytosis, impeding fluid reabsorption at the alveolar epithelium level; Conclusions: In experimental settings, with or without ALI, hypercapnia's immunomediated mechanisms exacerbate innate immune system impairment and disrupt the respiratory epithelium's repair and healing processes.

Groundwater flow and transport models are essential tools for assessing and quantifying the mi-gration of organic contaminants at polluted sites. Uncertainties in the hydrodynamic and transport parameters of the aquifer have a significant effect on model predictions. Uncertainties can be quantified with advanced sensitivity methods such as Sobol’s High Dimensional Model Reduction (HDMR) and Variogram Analysis of Response Surfaces (VARS). Here we present the application of VARS and HDMR to assess the global sensitivities of the outputs of a transient groundwater flow model of the Gállego alluvial aquifer which is located downstream the Sardas landfill in Huesca (Spain). The aquifer is subject to the tidal effects caused by the daily oscillations of the water level in the Sabiñánigo reservoir. Global sensitivities are analysed for hydraulic heads, aquifer/reservoir fluxes, groundwater Darcy velocity and hydraulic head calibration metrics. Input parameters in-clude aquifer hydraulic conductivities and specific storage, aquitard vertical hydraulic conductiv-ities, and boundary inflows and conductances. VARS, HDMR and graphical methods agree to identify the most influential parameters which for most of the outputs are the hydraulic conduc-tivities of the zones closest to the landfill, the vertical hydraulic conductivity of the most permeable zones of the aquitard, and the boundary inflow coming from the landfill. The sensitivity of heads and aquifer/reservoir fluxes with respect to specific storage change with time. The aquifer/reservoir flux when the reservoir level is high shows interactions between specific storage and aquitard conductivity. VARS and HDMR parameter rankings are similar for the most influential parameters. However, there are discrepancies for the less relevant parameters. The efficiency of VARS was demonstrated by achieving stable results with a relatively small number of simulations.

Considering animal welfare, the free-range laying hen farming model is increasingly gaining attention. However, in some countries, large-scale farming still relies on the cage-rearing model, making the focus on the welfare of caged laying hens equally important. To evaluate the health status of caged laying hens, a dataset comprising visible light and thermal infrared images was established for analyses, including morphological, thermographic, comb, and behavioural as-sessments, enabling a comprehensive evaluation of the hens' health, behaviour, and population counts. To address the issue of insufficient data samples in the health detection process for indi-vidual and group hens, a dataset named BClayinghens was constructed containing 61,133 images of visible light and thermal infrared images. The BClayinghens dataset was completed using three types of devices: smartphones, visible light cameras, and infrared thermal cameras. All thermal infrared images correspond to visible light images and have achieved positional alignment through coordinate correction. Additionally, the visible light images were annotated with chicken head labels, obtaining 63,693 chicken head labels, which can be directly used for training deep learning models for chicken head object detection and combined with corresponding thermal infrared data to analyze the temperature of the chicken heads. To enable the constructed deep-learning object detection and recognition models to adapt to different breeding environ-ments, various data enhancement methods such as rotation, shearing, colour enhancement, and noise addition were used for image processing. The BClayinghens dataset is important for ap-plying visible light images and corresponding thermal infrared images in the health detection, behavioural analysis, and counting of caged laying hens under large-scale farming.

Background. Respiratory distress syndrome (RDS) is the primary cause of respiratory failure in preterm infants, but it also affects 5-7% of term infants. Dysfunctions in pulmonary surfactant metabolism, resulting from mutations of the lung surfactant genes, are rare diseases, ranging from fatal neonatal RDS to interstitial lung disease, associated with increased morbidity and mortality. This study aims to clarify the clinical significance of ABCA3 variants found in a specific family case, as existing data in the literature is inconsistent. Material and methods: A family case report was conducted; targeted panel genetic testing identified a variant of the SFTPB gene and two variants of ABCA3 genes. Comprehensive research involving a systematic review of PubMed, Google Scholar databases, and genome browsers was used to clarify the pathogenicity of the two ABCA3 variants found in the index patient. Advanced prediction tools were employed to assess the pathogenicity of the two ABCA3 variants, ensuring the validity and reliability of our findings. Results: The index case exhibited fatal neonatal RDS. Genetic testing revealed the presence of the SFTPB p.Val267Ile variant, not previously reported, a benign variant based on family genetic testing and history. Additionally, two ABCA3 gene variants were identified: c.697C&gt;T, not yet reported, and c.838C&gt;T. These variants were found to affect ABCA3 protein function and were likely associated with neonatal RDS. Prediction tools and data from nine other cases in the literature supported this conclusion. Conclusions: Based on in silico predictors, analysis of the presented family, and cases described in the literature, it is reasonable to consider reclassifying the two ABCA3 variants identified in the index case as pathogenic/pathogenic. Reclassification will improve genetic counseling accuracy and facilitate correct diagnosis.

Isolation of new plant-derived lactic acid bacteria (LAB) is highly prioritized in developing novel starter cultures for plant-based fermentation. This study explores the diversity of LAB in Danish flowers and their potential use for plant-based food fermentation. 46 flower samples under 34 genera were collected for LAB isolation. By introducing an enrichment step, in total of 61 LAB strains were isolated and identified by using MALDI-TOF and 16S rRNA sequencing. These strains represent 24 species across 9 genera, predominantly Leuconostoc mesenteroides, Fructobacillus fructosus, Apilactobacillus ozensis, and Apilactobacillus kunkeei. Phenotypic screening for exo-cellular polysaccharide production revealed that 40 strains exhibited sliminess or ropiness on sucrose containing agar plate. HPLC analysis confirmed that all isolates produced exo-cellular polysaccharides containing glucose, fructose or galactose as sugar monomer. Therefore, the strains were glucan, fructan and galactan producers. The suitability of these strains for plant-based fermentations was characterized by using almond, oat and soy milk. The results showed successful acidification in all three types of plant-based matrices but only observed texture development in soy by Leuconostoc, Weissella, Lactococcus, Apilactobacillus, and Fructobacillus. The findings highlight the potential of flower-derived LAB strains for texture development in soy-based dairy alternatives.

Cholesterol homeostasis is pivotal for cellular function. Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1), also abbreviated as SOAT1, is an enzyme catalyzing the storage of excess cholesterol to cholesteryl esters. ACAT1 is an emerging target to treat diverse diseases including atherosclerosis, cancer, and neurodegenerative diseases. F12511 is a high affinity ACAT1 inhibitor. Previously, we developed a stealth liposome-based nanoparticle to encapsulate F12511 to enhance its delivery to the brain and showed its efficacy in treating a mouse model for Alzheimer’s disease (AD). In this study, we introduce F26, a close derivative of F12511 metabolite in rats. F26 was encapsulated in the same DSPE-PEG2000/phosphatidylcholine (PC) liposome-based nanoparticle system. We employed various in vitro and in vivo methodologies to assess F26's efficacy and toxicity compared to F12511. Results demonstrate that F26 is more effective and durable than F12511 in inhibiting ACAT1, in both mouse embryonic fibroblasts (MEFs) and in multiple mouse tissues including the brain tissues, without exhibiting any overt systemic or neurotoxic effects. This study demonstrates the superior pharmacokinetic and safety profile of F26 in wild-type mice, and suggests its therapeutic potential against various neurodegenerative diseases including AD.

Background: Medication errors often stem from incomplete or incorrect transfer of drug information during reviews. To enhance medication review processes, a collaborative healthcare team, including a pharmacist in the surgical ward, is essential. This study aimed to identify the frequency and the kind of intentional and unintentional discrepancies related to the prescriptions within two surgical wards. Methods: A prospective observational study was conducted among adult patients admitted to two surgical settings. The patients were selected between May 30th and November 30th, 2021. The study followed a three-phase structure: patient selection, medication review to identify discrepancies and DRPs, and the detection of any such issues in the discharge letter. Results: The most frequent types of discrepancies collected were substitutions (60.9%) for the Endocrinological Surgery and omissions for General Surgery (53.4%). In Endocrinological Surgery, 45.9% of cases exhibited class C drug interactions. In General Surgery, class D drug interactions were predominantly observed (54.1%), with 93.3% attributed to drugs carrying an elevated risk of prolonging the QT interval. Conclusions: Frequently, the medication review process is superficially carried out, introducing errors that may adversely affect patient health. This study explores the potential positive impact of involving the clinical pharmacist in identifying and managing discrepancies and DRPs.

Objectives: To compare the effects of high-velocity resistance training to slow-velocity re-sistance training on neuromuscular and functional parameters and to analyze the relationship between changes in walking speed and improvements in neuromuscular parameters following intervetions. Methods: 40 participants were randomly assigned to either a high-speed resistance training group (GHS, n = 18; age = 80.41 ± 10.12 years; BMI = 23.81 ± 3.45 kg/m²) or a low-speed resistance training group (GLS, n = 22; age = 82.89 ± 5.32 years; BMI = 23.81 ± 3.45 kg/m²). Before and after the interventions, gait speed (m/s) was assessed using a 10-minute walking test, and relative maximal force (Relative F max, N/kg) was evaluated during maximal voluntary isometric con-traction of the plantar flexors. From the force-time curve, early (0 – 50 ms) and late (100 – 200 ms) rates of force development (RFD) were extracted from the linear slopes (Δ force / Δ time). Results: Gait speed significantly improved in both groups (p < 0.05). However, the improvement was more pronounced in the GHS compared to the GLS (p < 0.05). Relative Fmax showed a more significant increase in the GLS than in the GHS (p < 0.05). Moreover, a significant 10% increase in early RFD in the GLS and a 20.1% increase in the GHS were observed (p < 0.05). The improvement in early RFD was greater in the GHS (p < 0.05). Additionally, late RFD improved significantly only in the GHS (+20.4%, p < 0.05). Conclusion: High-velocity resistance training appears particularly effective in improving the ability to rapidly generate force, which is essential for many daily activities re-quiring explosive movements and quick responses.

For quantitative determination of honokiol (HNK) and metformin hydrochloride (M-HCl) by HPLC from formulations and from dissolution studies, a QbD approach using three factors - three levels design was implemented to optimize the chromatographic conditions. To study the impact of each variable on the peak area of both compounds and retention time of last compound eluted, the 3D response surface plots were developed. HNK and M-HCl were separated on a Thermoscientific ODS Hypersyl TM (250 x 4.6 mm, 5 μm) column mantained at 30 C, using 0.02 M acetate buffer (pH = 3) / methanol (15 / 85, v / v) as mobile phase with a flow rate of 1 mL/min. The injected volume was 20 L, and the detection wavelengths were 256 nm for HNK and 236 nm for M-HCl. The validation of proposed method showed a linearity range of 4 – 1200 μg/mL for M-HCl (r2 = 0.9992) and 1 – 300 μg/mL for HNK (r2 = 0.9998), good precision (RSD &lt; 2% for both HNK and M-HCl, in intra- and inter-day studies) and accuracy (mean recovery = 100.09% in the range 99.80 – 100.43% for M-HCl and mean recovery = 100.12% in the range 99.70 – 100.38% for HNK). The environmentally friendly nature of the method was confirmed by the evaluation of the method’s greenness. The proposed method was applied for the determination of HNK and M-HCl from oral dosage forms and in dissolution studies.

Blood vessels are essential for maintaining tumor growth, progression, and metastasis, yet the tumor vasculature is under a constant state of remodeling. Since the tumor vasculature is an attractive therapeutic target, there is a need to predict the dynamic changes in intratumoral fluid pressure and velocity which occur across the tumor microenvironment (TME). The goal of this study is to get insight into perfusion anisotropy within lung tumors. To achieve this goal, we used the perfusion marker Hoechst 33342 and vascular endothelial marker CD31 to stain tumor sections from C57BL/6 mice harboring Lewis Lung Carcinoma tumors on their flank. Vasculature, capillary diameter, and permeability distribution were extracted at different time points along the tumor growth curve. A computational model was generated applying a unique modeling approach based on the smeared physical fields (Kojic Transport Model, KTM). KTM predicts spatial and temporal changes in intratumoral pressure and fluid velocity within the growing tumor. Anisotropic perfusion occurs within two domains - capillary and extracellular space. Anisotropy in tumor structure causes nonuniform distribution of pressure and fluid velocity. These results provide insights regarding local vascular distribution for optimal drug dosing and delivery to better predict distribution and duration of retention within the TME.

The objective of this paper was to study the expression pattern of the GLOD4 gene in the testis and its regulatory effect on testicular cells. Currently, the regulated mechanism through are unclear. Here, we explored how GLOD4 functions in goat leydig cells to enhance our understanding of spermatogenesis and improve reproduction in breeding rams. In this study, we demonstrated that the localization of GLOD4 in testicular cells using immunohistochemistry and subcellular localization analyses. Subsequently, we analyzed the GLOD4 expression pattern in 4 age-based groups (0, 6, 12, and 18 months old) using real-time quantitative polymerase chain reaction (qRT‒PCR) and protein blotting. Finally, we performed GLOD4 gene silencing and overexpression studies in testicular cells from goats and explored the effects of GLOD4 on cell proliferation, the cell cycle, steroid hormone secretion and the expression of candidate testosterone hormone-regulated genes. GLOD4 was mainly expressed in testicular leydig cells, and the subcellular localization results showed that the GLOD4 protein was mainly localized in the cytoplasm and nucleus. Silencing of GLOD4 significantly suppressed the mRNA expression levels of the testosterone secretion-related genes CYP11A1, 3β-HSD and CYP17A1 and the mRNA expression levels of cell-cycle related genes CDK6, PCNA, and Cyclin E. Moreover, the cell cycle was blocked at the G2/M phase after GLOD4 silencing, which significantly suppressed testosterone secretion. In contrast, GLOD4 overexpression significantly increased the mRNA expression levels of the testosterone secretion-related genes CYP11A1, 3β-HSD, and CYP17A1 and increased the expression of the cell-cycle related genes CDK6, PCNA, and Cyclin E. Moreover, GLOD4 overexpression promoted the cell cycle from G0/G1 phases to enter the S phase and G2/M phases,promoted the secretion of testosterone. Taken together, our experimental results indicate that GLOD4 may affect the development of cells in Qianbei Ma goats of different ages by influencing the cell cycle, Proliferation and testosterone hormone synthesis. These findings enhance our understanding of the functions of GLOD4 in the cells of goats.

Fish kills in Southeast Asia are frequently associated with harmful algal blooms (HABs) and cause significant ecological and economic impacts. This paper serves as a review of fish kill events with focus on those related to HABs within the region. It examines the causative algal species, known mechanisms of fish mortality, and socio-economic consequences. Fish kills have been reported across multiple countries within Southeast Asia, with notable hotspots in the Philippines, Malaysia, Singapore, Indonesia, and Thailand. The common harmful microalgal species span a diverse group including dinoflagellates (Karenia spp., Karlodinium spp., Margalefidinium polykrikoides, Noctiluca scintillans), raphidophytes (Chattonella spp.), diatoms (Skeletonema spp. and Chaetoceros spp.), and cyanobacteria (Trichodesmium spp.). These microalgae lead to fish kills through mechanisms such as hypoxia, physical gill damage, and ichthyotoxin production. Freshwater fish kills linked to HABs have also been documented for the Philippines, but there is no or limited information for the region. Our review highlights the widespread and recurring nature of fish kills, their impact on fisheries and aquaculture, and challenges in managing and mitigating their effects. There are efforts at enhancing management and mitigation using clay and early-warning systems. However, it is essential to further improve monitoring efforts, the development and deployment of early-warning systems, and viable and holistic mitigation strategies to protect the region’s aquatic resources and dependent communities, especially as aquaculture and coastal development are increasing concurrent with a changing climate that can exacerbate the risks of fish kills and HABs in Southeast Asia.

Background: The study was conducted to investigate if the mRNA vaccine technology could be adapted for the ectothermic vertebrate Atlantic salmon (Salmo salar). The lipid nanoparticle (LNP) technology has been developed and optimized for mRNA vaccines in mammals, stabilizing mRNA and facilitating delivery into cells. However, its utility at the temperature and specific biological environment in ectotherms remains unclear. In addition, it is unknown if modified mRNA containing non-canonical nucleotides can correctly translate in salmonid cells. Methods: We used an mRNA transcript coding for enhanced green fluorescence protein, flanked by the untranslated regions of the hemagglutinin-esterase gene of infectious salmon anemia virus, and a 120-base-long poly(A) tail. The mRNA was generated by in vitro transcription where uridine residues were replaced with N1-methyl-pseudouridines, and then encapsulated in LNPs. Results: When transfected into the salmonid cell line CHH-1, the mRNA-LNP construct induced expression of EGFP. Furthermore, when mRNA-LNPs were injected intramuscularly into salmon, in vivo protein expression was demonstrated by immunohistochemistry. EGFP was observed in cells infiltrating the space between the muscle cells in a focal inflammatory response. Conclusion: The results indicate that the N1-methyl-pseudouridine modified mRNA encapsulated in LNPs can be used to express antigens of interest in salmonid fish.

The growing interest in Kv7.2/7.3 agonists originates from the involvement of these channels in several brain hyperexcitability disorders. In particular, Kv7.2/7.3 mutants have been clearly associated with epileptic encephalopathies (DEE) as well as with a spectrum of focal epilepsy disorders, often associated with developmental plateauing or regression. Nevertheless, there is a lack of available therapeutic options, considering that retigabine, the only molecule used in clinic as broad-spectrum Kv7 agonist, has been withdrawn from the market in the late 2016. This is why several efforts have been made both by both academia and industry in the search for suitable chemotypes acting as Kv7.2/7.3 agonists. In this context, in silico methods have played a major role, since the precise structures of different Kv7 homotetramers have been only recently disclosed. In the present review the computational methods used for the design of Kv.7.2/7.3 small molecule agonists and the underlying medicinal chemistry are discussed in the context of their biological and structure-function properties.

In this study, the mechanical and piezoresistive properties of mortars reinforced with carbon nanotubes (CNTs) and carbon micro fibers (CMFs) are determined. Silica fume as well as a polymer with polyalkylene glycol graft chains were used as dispersant agents for the CNTs and CMFs incorporation into the cement paste. The mechanical properties of the mortar composites were investigated in respect to their flexural and compressive strength. A four-probe method was used for the estimation of their piezoresistive response. The test outcomes revealed that the combination of the dispersant agents along with a low content of CNTs and CMF by weight of cement (bwoc) result in the production of a stronger mortar with enhanced mechanical performance and durability. More specifically, there was an increase in flexural and compressive strength up to 38% and 88%, respectively. Moreover, the piezoresistive response of the reinforced cementitious materials was attributed to the variation of electrical resistivity due to tunneling transport of electrons stemming from two different mechanisms due to the incorporation of the conductive admixtures (CNTs and CMF). This work aims to contribute to the progress acceleration in the field of developing structural materials with self-sensing and electrical actuation related properties.