This paper introduces new improvements to the modified version of the BIRECT (BI secting RECTangles) algorithm referred to as BIRECTv. We explore various approaches, by first including a grouping strategy for hyper-rectangles having almost the same sizes by categorizing them into different classes. Therefore constraining them not to exceed a certain pre-defined threshold (a small positive value to define the tolerance level). This approach allows for more efficient computation and can be particularly useful when dealing with a large number of hyper-rectangles with varying sizes. To avoid over-sampling, and preventing redundant or excessive sampling, at some shared vertices in descendant subregions, a particular vertex database is used to limit the number of samples taken within each subregion to two. The experimental investigation shows that these improvements have a positive impact on the performance of the BIRECTv(imp.) algorithm and the proposal is a promising global optimization algorithm compared to the original BIRECTv algorithm and its variants. Additionally, the BIRECTv(imp.) algorithm showed particular efficacy in solving high-dimensional problems.

Recently, considerable work has been directed at development of a ultra-compact X-ray free-electron laser based on emerging techniques in high field cryogenic acceleration, with attendant dramatic improvements in electron beam brightness, and state-of-the-art concepts in beam dynamics, magnetic undulators, and X-ray optics. A full conceptual design of a 1 nm XFEL with a length and cost over an order of magnitude below current XFELs has resulted from this effort. This instrument has been developed with an emphasis on permitting exploratory scientific research in a wide variety of fields in a university setting. Concurrently, compact FELs are being urgently developed for use as an instrument to enable next generation chip manufacturing through use as a high flux, few-nm lithography source. This new role suggests consideration of XFELs to addressed urgently emerging demands in this sector, as identified by recent national need studies, for new radiation sources aimed at chip manufacturing: a coherent hard X-ray source which enables frontier metrology methods. Indeed, it has been shown that one may use coherent X-rays to perform 10 nm-class resolution surveys of macroscopic, cm-scale structures such as chips, using ptychographic laminography. As the XFEL is a very promising candidate for realizing such methods, we present here an analysis of the issues and likely solutions associated with extending the UCXFEL to harder X-rays (above 7 keV), much higher fluxes and levels of coherence, and methods of applying such a source for ptychographic laminography to micro-electronic device measurements. We discuss the development path to move the concept to rapid realization of a transformative FEL-based application, outlining FEL and metrology system challenges.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a complex gastrointestinal disorder with a multifactorial etiology, including environmental triggers, autoimmune mechanisms, and genetic predisposition. Despite advancements in therapeutic strategies for IBD, its associated mortality rate continues to rise, which is often attributed to unforeseen side effects of conventional treatments. In this context, we explored the potential of Ecklonia cava extract (ECE) derived from an edible marine alga known for its anti-inflammatory and antioxidant properties in mitigating IBD. This study investigated the effectiveness of ECE as a preventive agent in a murine model of dextran sulfate sodium (DSS)-induced colitis. Our findings revealed that pretreatment with ECE significantly ameliorated colitis severity as evidenced by increased colon length, reduced spleen weight, and histological improvements demonstrated by immunohistochemical analysis. Furthermore, ECE significantly attenuated the upregulation of inflammatory cytokines and mediators and the infiltration of immune cells known to be prominent features of colitis in mice. Notably, ECE restored dysbiosis of intestinal microflora and aided in the recovery of damaged intestinal mucosa. Mechanistically, ECE exhibited protective effects against pathogenic colitis by inhibiting the NLRP3/NF-κB pathway known to be pivotal regulators in the inflammatory signaling cascade. These compelling results suggest that ECE holds promise as a potential candidate for IBD prevention. It might be developed into a functional food for promoting gastrointestinal health. This research sheds light on the preventive potential of natural compounds like ECE in the management of IBD, offering a safer and more effective approach to combating this challenging disease.

Celiac disease is an autoimmune disease triggered by oral ingestion of gluten, with certain gluten residues resistant to digestive tract enzymes. Within the duodenum, the remaining peptides incite immunogenic responses, including the generation of autoantibodies and inflammation, leading to irreversible damage. Our previous exploration unveiled a glutenase called Bga1903 derived from the Gram-negative bacterium Burkholderia gladioli. The cleavage pattern of Bga1903 indicated its moderate ability to mitigate the toxicity of pro-immunogenic peptides. The crystal structure of Bga1903, along with the identification of subsites within its active site, was determined. To improve its substrate specificity toward prevalent motifs like QPQ within gluten peptides, the active site of Bga1903 underwent site-directed mutagenesis according to structural insights and enzymatic kinetics. Among the double-site mutants, E380Q/S387L exhibits an approximately 38-fold increase in its specificity constant toward the QPQ sequence, favoring glutamines at the P1 and P3 positions compared to the wild type. Not only does the heightened specificity of E380Q/S387L improve the hydrolytic activity against pro-immunogenic peptides, but also holds this version of the enzyme as a promising candidate as an oral therapy enzyme for celiac disease.

The growing adoption of distributed energy production technologies, and the potential of energy underutilization when it is produced by non-connected groups, has raised interest in ‘sharing economy’ concepts in the electricity sector. We suggest that mechanisms, such as peer-to-peer (P2P) energy trading, will allow users to exchange their surplus energy for mutual benefits, stimulate the adoption of renewable energy, encourage communities to ‘democratically’ control their own energy supplies for local development, and improved energy efficiency, and create many other benefits This approach is receiving increasing attention across the world, particularly in Germany, the Netherlands and Australia. Nevertheless, the actual development and implementation of these platforms is slow and mostly limited to trial activities. This study investigates the challenges and barriers facing P2P energy trading developments based on previous academic and industry studies. We provide a comprehensive multidimensional barrier analysis through a PESTLE approach to assess the barriers from a variety of perspectives, including the political (P), economic (E), social (S), technological (T), legal (L), and environmental (E) aspects. This approach clarifies the many intersecting problem fields of P2P trading in renewable energy, and the paper identifies a list of such barriers, and discusses the prospects for addressing these issues. We also elaborate on the importance of incentive-based P2P market design.

Studies involving vortex in hybrid superconducting devices and their interaction with different components inside the sample are an important issue to reach higher values of their critical parameters in superconducting materials. The vortex distribution on each side of sample with different fundamental parameters, such as temperature T, penetration depth λ, coherence length ξ, electron mass m and the order parameter Ψ, may help to improve the superconducting properties. Thus, in this work, we used the modified Ginzburg-Landau theory to investigate hybrid superconductor (HS), but also to provide a highly tunable and adjustable theoretical tool to theoretically explain the experimental results involving HS, in order to study the vortex behaviour in superconductors of mesoscopic dimensions with extremely differences among their fundamentals parameters. Therefore, we evaluated the influence of HS on vortex configuration and their effects in the field-dependent magnetization. The results show that the during the increment of applied magnetic field H the diamagnetic response of HS, Meissner effect, include additional jumps of magnetization while diamagnetism continues its increase in the sample. In addition, the differences among parameters, create an interface between both components, two different magnitudes of supercurrent and vortex sizes producing a lower degradation of local superconductivity, which increase the upper critical field. On the other hand, this type HS with differences of parameters on both sides can be used to control the vortex movement in the selected superconducting region sample with more accuracy.

This paper investigates if the polar groups induced by a plasma treatment can increase the lap shear strength of laser joined metal and plastic hybrids. Optimal laser joining parameters for cold-rolled AISI304 – Polyamide 6.6 and sandblasted AISI304 - Polypropylene hybrids are developed. The OWRK-method was utilized to identify the change in surface free energy of a low-pressure plasma treatment. Plasma treated samples were joined and tested. The fractured surfaces were investigated via light microscopy and SEM. The arithmetic means of the plasma treated hybrids lap shear strength with polyamide 6.6 varied slightly but all measured values were within the range of the untreated samples. The lap shear strengths of the polypropylene hybrids were significantly reduced. This was attributed to an overaging and the development of low molecular weight oxidized materials which lead to a weak boundary layer. No correlation between surface free energy and the lap shear strength could be found.

The blood–brain barrier (BBB) plays pivotal roles in synaptic and neuronal functioning by sealing the space between adjacent microvascular endothelial cells. BBB breakdown is present in patients with mild cognitive impairment (MCI) or Alzheimer disease (AD). Claudin-5 (CLDN-5) is a tetra-spanning protein essential for sealing the intercellular space between adjacent endothelial cells in the BBB. In this study, we developed a blood-based assay for CLDN-5 and investigated its diagnostic utility by using 100 cognitively normal (control) subjects, 100 patients with MCI, and 100 patients with AD. Plasma CLDN-5 levels were increased in patients with AD (3.08 ng/mL) compared with controls (2.77 ng/mL). Plasma levels of phosphorylated tau (pTau181), a biomarker of pathological tau, were elevated in patients with MCI or AD (2.86 and 4.20 pg/mL, respectively) compared with control subjects (1.81 pg/mL). In patients with MCI or AD, plasma levels of CLDN-5—but not pTau181—decreased with age, suggesting some age-dependent BBB changes in MCI and AD. These findings suggest that plasma CLDN-5 may a potential biochemical marker for the diagnosis of MCI and AD.

Background: Malnutrition was associated with worse survival outcomes, impaired quality of life, and deteriorated performance status across various cancer types. We aimed to identify risk factors for malnutrition in patients with epithelial ovarian(EOC) and impact on survival. Methods: In our prospective study, we included the patients with primary and recurrent EOC, tubal or peritoneal cancer conducted. We assessed serum laboratory parameters, body mass index, nutritional risk index, nutritional risk screening score(NRS-2002), and bio-electrical impedance analysis. Results: We recruited a total of 152. Patients >65 years-old, with ascites of >500 ml, or with platinum-resistant EOC showed statistically significant increased risk of malnutrition when evaluated by NRS-2002(p-values = 0.014, 0.001, and 0.007, respectively). An NRS-2002<3 was an independent predictive factor for complete tumor resectability (p=0.009). The patients with NRS-2002≥3 had a median overall survival(OS) of seven months (95% CI=0-24 months), as compared to the patients with NRS-2002<3 where median OS was 46 months(p=0,001). Phase angle(PhAα)≤ 4.5 was the strongest predictor of OS. Conclusion: Malnutrition is an independent predictor of incomplete cytoreduction in study population. It is an independent prognostic factor for poor OS. Preoperative nutritional assessment is an effective tool in identification of high-risk groups within EOC characterized by poor clinical outcome.

Background: This study retrospective evaluates patients with stage IV melanoma treated with Nivolumab and Ipilimumab combination therapy from two regional oncology centers from Romania between the years of 2019 up to the end of 2022. Methods: The data were analyzed in SAS for Windows, V9.4. The survival curves were estimated using the Kaplan-Meier method, and survival distributions were compared with log-rank test. The effects of the main clinical and pathological variables on OS and PFS were investigated with Cox regression. Results: Kaplan-Meier curve of OS in all evaluable patients enrolled in the study resulted in a median OS of 346 days (95% CI: 150-NA) and a median PFS of 211 days (95% CI: 113-430). 45.3% of the patients experienced adverse events during the Nivolumab + Ipilimumab treatment with some of them having multiple organ systems involved. Discussion: The OS values were lower than that reported in approval clinical trials, but the results show a marked improvement when comparing to results obtained by chemotherapy regimens previously used in these scenarios. Conclusion: This study provides real-world insights into the survival data and safety profiles of combination therapy with anti-PD-1 antibodies and anti-CTLA-4 antibodies.

Band structure calculations using the spin-polarized relativistic Korringa-Kohn-Rostoker (SPRKKR) band structure method have been performed to determine the intrinsic magnetic properties (magnetic moments, magneto-crystalline anisotropy -MAE and Curie temperatures) of the Fe5-x-yCoxMySiB2 (M = Re, W) alloys. The general gradient approximation for ex-change-correlation potential and the atomic sphere approximation (GGA ASA) have been em-ployed. Previous studies showed that the Co doping is turning the in-plane into axial anisotropy for a certain doping range, whilst the 5d doping enables a strong spin-orbit coupling of Fe-3d and M-5d states which is needed to enhance the MAE. The theoretical calculations aim to find the dependence of the anisotropy constant K1 for combined Co and M doping, building a two-dimensional (2D) map of K1 for 0 ≤ x ≤ 2 and 0 ≤ y ≤ 1. Similar theoretical 2D maps for magnetization and Curie temperature vs. Co and M content (M = W and Re) have been built, allowing to select alloy compositions with enhanced values of uniaxial anisotropy, magnetization and Curie temperature. Magnetic properties of Fe4.1W0.9SiB2 alloy that meets the selection criteria for axial anisotropy K1 > 0.2 meV/f.u., Curie temperature Tc > 800 K determined by mean field approach and magnetization µ0Ms > 1 T are discussed.

Cancer remains as a worldwide cause of death. Investigational research efforts have included the administration of tumors-derived extracts to healthy animals. Having previously demonstrated that administration of non-transmissible, human cancers-derived homogenates induced malignant tumors in mice; we examined here the consequences of administering 50 or 100 µg of protein of crude homogenates from samples of mammary carcinoma, pancreatic adenocarcinoma, and melanoma. The protocol conceived six inoculations per week during three months. Concurrent control group received homogenates of healthy donor skin cosmetic surgery fragments. Mammary carcinoma homogenate administration did not provoke animals’ deterioration or mortality. Multiple foci of lung adenocarcinomas with broad expression of malignity histomarkers, coexisting with small cell-like carcinomas were found. Disseminated cells, positive to classic epithelial markers were detected in lymphoid nodes. Pancreas tumor and melanoma homogenates administrations severely deteriorated animals’ health. Pancreas tumor induced lung poorly-differentiated adenocarcinomas, as a remarkable pancreatic islets hyperplasia. Melanoma affected lungs with atypical adenomatous hyperplasia and solid pseudopapillary adenocarcinoma. Giant atypical hepatocytes with variegated nuclei were also observed. Kidney parenchyma exhibited dispersed foci of neoplastic cells within a desmoplastic matrix. A noticeable nuclear overlapping with hyperchromatic nuclei, mitotic figures, and prominent nuclear atypia was identified in epidermal cells. None of these changes were ever detected in any mouse of the control groups. This study confirms and extends our hypothesis that tumor homogenates contain and may act as a vector for “malignancy drivers”, which ultimately implement a carcinogenesis process in otherwise healthy mice.

.Celiac disease (CeD) is a chronic, autoimmune disorder triggered by the ingestion of gluten, affecting around 1% of the global population. It is a multifactorial disease involving both genetics and environ-mental factors. Nowadays, the only available treatment for CeD is a life-long gluten-free diet (GFD), which can cause a significant burden for patients, since symptoms and mucosal injury can persist de-spite apparent compliance with a GFD. That could also lead to psychological consequences and affect the quality of life of these patients. Thankfully, recent advances in understanding the pathogenesis of CeD and the availability of various targets have made it feasible to explore pharmaceutical treatments specific to CeD. Recently, the FDA has highlighted the unmet needs of adult patients on GFD who expe-rience ongoing symptoms attributed to CeD and also show persistent duodenal villous atrophy. This re-view will outline the limitations of a GFD, describe the targets of potential novel treatment of CeD and provide an overview of the primary clinical trials involving oral and injectable agents for a non-dietary treatment of CeD.

Accurate pathogenic detection in wastewater is critical for safeguarding public health and the environment. However, the presence of free nucleic acids in wastewater samples poses significant challenges to molecular detection accuracy. This comprehensive review explores the current status and future potential of pretreatment methods to remove free nucleic acids from wastewater samples. The study contributes a comprehensive analysis of the mechanisms, strengths, and limitations of various pretreatment approaches, including physical, chemical, and enzymatic processes. The effect of various factors on the removal efficiency of these pretreatment methods is also discussed. This review enhances our comprehension of pretreatment techniques and their vital role in achieving precise pathogenic detection in complex wastewater matrices. Furthermore, it outlines future perspectives and developments for improving the speed and effectiveness of pathogenic detection, contributing significantly to disease surveillance, early warning systems, and environmental protection.

In this study, Plasma-Activated Water (PAW) was synthesized using a coaxial Dielectric Barrier Discharge (DBD) reactor, benefiting from the elevated capacity of air-flow-assisted DBD discharges to enhance nitrogen-based species concentration. By manipulating operational parameters, including gas flow rate, activation time, and DI water volume, we achieved significant concentrations of Reactive Oxygen and Nitrogen Species (RONS). As a result, the PAW obtained displayed pronounced physicochemical attributes: a pH of 2.06, an ORP of 275mV, conductivity of 3mS/cm, and TDS of 1200 mg/L. A pivotal aspect of this research was the evaluation of the reactor's efficiency, as indicated by metrics like the specific input energy and ozone efficiency yield. The antimicrobial potential of the PAW was also assessed against pathogenic microbes, with remarkable reductions in viability for both Staphylococcus aureus and Escherichia coli (99.99%) and a more moderate decrease for Candida albicans (37%). These findings underscore the capability of the coaxial DBD reactor in crafting high-quality PAW with significant antimicrobial properties, necessitating further studies to validate its broad-spectrum and safe application.

Serologic measures of tissue transglutaminase (tTG) immunoglobulin A (IgA) and deamidated gliadin peptide (DGP) IgA and immunoglobulin G (IgG) are hallmark tests utilized when diagnosing individuals for celiac disease (CeD) and for monitoring adherence to a gluten-free diet (GFD), currently the only available treatment for CeD. We address two issues in this study: (i) the relapse to seropositivity for CeD patients who resume a gluten containing diet and (ii) the correlation between two different tTG-IgA assays near the upper limit of normal (ULN) designated thresholds. Regarding the first issue, often a suspected CeD individual is put back on a gluten diet to return to their serologic levels. However, we show it requires a substantial amount of gluten for serology to return to a positive level. For example, in one study of 22 patients treated with placebo and taking 84 g of gluten over 6 weeks, only 2 converted from seronegative to seroposi-tive for tTG-IgA. Regarding the second topic, we compare the relationship for different serologic assays, namely tTG-IgA AB (recombinant, ULN=4 Units/mL) vs. tTG-IgA (non-recombinant, ULN=20 Units). There is a strong correlation by both measurements as evidenced by a Pearson coefficient of R = 0.8584. However, we observed that the cross-correlation in terms of sensitivity and specificity improved substantially by using an ULN value of 3 instead of 4 for the tTG-IgA AB (recombinant) assay. This result suggests that assay thresholds used for initial diagnosis in patients who have not yet started a GFD may need to be adjusted for monitoring and in the setting of a diagnostic gluten challenge.

Central Nervous System (CNS) cancers pose a formidable challenge in the medical world, characterized by aggressive behaviors and limited therapeutic options. The emergence of nanomedicine has offered new hope in CNS cancer treatment. The COVID-19 pandemic has further accelerated the need for innovative therapeutic strategies, emphasizing the significance of nanomedicine in this era. This mini review explores the current status of nanomedicine in CNS cancer therapy, with a particular focus on the post-COVID-19 landscape. We discuss the unique challenges presented by CNS cancers, the potential of nanomedicine in overcoming these challenges, and the recent developments in the field. Additionally, we highlight the lessons learned from the pandemic and how they can be applied to improve CNS cancer therapeutics. We also shed light on the evolving regulatory landscape and the prospects of personalized nanomedicine in CNS cancer treatment. The integration of nanomedicine in CNS cancer therapy is becoming increasingly promising, and its role in the post-COVID-19 era is poised to shape the future of neuro-oncology.

The emergence of antimicrobial resistance remains one of the greatest public health concerns. Biofilm formation has been postulated as a mechanism of microbial pathogens to resist antimicrobial agents. Lactic Acid Bacteria (LAB) and their metabolites have been proposed to combat bacterial biofilms, due to their antimicrobial activity. In this vein, the aim of the present study was to investigate the biofilm removal potential of cell-free supernatant (CFS) of five wild-type Lacticaseibacillus rhamnosus LAB strains, isolated from Greek natural products, in comparison to the commercial available L. rhamnosus GG strain, formed by common foodborne pathogens (Salmonella Enteritidis, Salmonella Typhimurium, Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus). Biofilm removal activity of LAB was assessed on two-days mature biofilm using a microtiter plate-based procedure. Both non-neutralized and neutralized CFSs removed biofilms in a concentration-dependent manner. Biofilm removal activity of the non-neutralized CFSs was significantly higher compared to the neutralized CFSs, as expected, ranging 40 – 90% and 10 – 78%, respectively. Biofilm removal efficiency of L. rhamnosus OLXAL-3 was signifanctly higher among the wild-type L. rhamnosus strains tested (20 – 100% v/v). In conclusion, our results suggested the great potential of application of wild-type Lacticaseibacillus rhamnosus strains CFSs as effective natural agents against pathogenic bacterial biofilms.

In the aerospace sector, structural and non-structural components are usually subjected to a wide range of environmental conditions. Although lightweight, the use of composite parts for these applications is restricted, due to their poor performance in severe environmental conditions. Specifically, moisture can seriously damage the materials' performance, reducing their mechan-ical, thermal, electrical, and physical properties as well as the service time. A strategy to improve the materials’ resistance in humid environments is the use of protective lightweight barrier coatings to reduce the diffusion of gases and/or liquids in composites. Nanolamellar nanocom-posite characterized by the high in-plane orientation of nanoplatelets effectively works as barrier structures by generating tortuous paths for molecule diffusion. In this work, the effectiveness of protection against water uptake of nanocomposites reinforced with Graphite NanoPlatelets (GNPs) at high filler content (70, 80 and 90%wt) for Kevlar sandwich panels of a nacelle engine of an ATR42 aircraft has been investigated. Moisture uptake and Ground Air Ground (GAG) tests were carried out in an environmental chamber to reproduce temperature and relative humidity profiles representative of a real-scale application for a regional aircraft composite part. The high filler content of the graphene films ensures a high level of tortuosity by delaying and reducing moisture absorption by –71% compared to the unprotected panel, showing good barrier properties.

Aryl chlorides and bromides in the presence of NHC palladium hydroxo dimers of the type [{Pd(µ-OH)Cl(NHC)}2] (where NHC = IPr, SIPr, IMes, SIMes) undergo an efficient and selective Sonogashira cross-coupling with terminal acetylenes. For the coupling of 4-chlorotoluene with phenylacetylene TON = 560000 was observed. The procedure enables high-throughput and selective synthesis of a broad spectrum of unsymmetrically substituted 1,2-diarylacetylenes. Nearly a quantitative amount of HCl was detected within cross-coupling products. Water plays the role of the base and is regenerated in the process so that it does not have to be used in stoichiometric amounts (relative to the limiting reactant). Generation of the active Pd(0) complex proceeds via ethanol oxidation.

The farnesoid X receptor (FXR)/βKlotho/fibroblast growth factors (FGFs) pathway is crucial for maintaining the intestinal barrier and preventing colorectal cancer (CRC). We used an FXR ago-nist, GW4064, and FXR knockout (KO) mice to investigate the role of FXR/Klothos/FGFs pathways in lipopolysaccharide (LPS)-induced intestinal barrier dysfunction and colon carcinogenesis. The results showed that upregulation of FXR in enterocytes effectively ameliorated intestinal tight junction markers (claudin1, Zonula occludens-1), inflammation, and bile acid levels, thereby protecting mice from intestinal barrier dysfunction and colon carcinogenesis. GW4064 treatment increased FXR, αKlotho, βKlotho, FGF19, FGF21, and FGF23 in wild-type mice exposed to LPS, while FXR KO mice had decreased levels. FXR KO mice exhibited elevated colon cancer markers (β-catenin, LGR5, CD44, CD34, Cyclin D1) under LPS, underscoring the pivotal role of FXR in inhibiting the development of colon tumorigenesis. The varying gut microbiota responses in FXR KO mice versus wild-type mice post-LPS exposure emphasize the pivotal role of FXR in pre-serving intestinal microbial health, involving Bacteroides thetaiotaomicron, Bacteroides acidifaciens, and Helicobacter hepaticus. Our study validates the effectiveness of GW4064 in alleviating LPS-induced disruptions to the intestinal barrier and colon carcinogenesis, emphasizing the importance of the FXR/αKlotho/βKlotho/FGFs pathway and the interplay between bile acids and gut microbiota.

The work carried out first-principles calculations within the framework of density functional theory to study the structural stability of the CsSnI₃ compound and the influence of phase transitions on their electronic and optical properties. Using the GGA and SCAN functionals, the relaxed structures of the CsSnI₃ phases were obtained and their geometric characteristics were assessed. Using the Phonopy code based on VASP, calculations of phonon and thermodynamic properties were performed, and the temperatures of phase transitions of CsSnI₃ were determined. The temperature dependences of the thermodynamic parameters α-, β-, γ- and δ-phases of CsSnI₃ were analyzed. The trends in free energy, entropy, enthalpy, heat of formation energy and heat capacity were justified in terms of the pattern of changes in the total energy of the four phases of CsSnI₃ from VASP calculations. It is shown that at 0 K the non-perovskite structure of the CsSnI₃ compound (δ-CsSnI₃) is the most stable (followed by γ-CsSnI₃), and the tetragonal phase (β) is quite unstable, having the highest energy among the perovskite phases. It was revealed that at temperatures above 450 K the tetragonal phase becomes stable, and when the temperature drops, it transforms into the cubic phase (α-CsSnI₃). The phase transition between the β and γ phase of perovskite occurs in the range of 300-320 K, and at 320 K a black-yellow transformation of CsSnI₃ occurs in which the cubic phase (black perovskite) undergoes a phase transition to a non-perovskite conformation (yellow phase). The presence of temperature phase transitions between two orthorhombic phases of CsSnI₃ at 360 K was discovered, although direct transitions of the α⟷γ and γ⟷δ types have not yet been reported in any experiment, except for γ→δ transitions under the influence of moisture. Based on well-relaxed structures (from the SCAN calculations), the band gap widths for four CsSnI₃ phases were calculated and compared with experimental measurements. Electronic properties and Fermi level shifts as a result of phase transformations of CsSnI₃ were assessed using the HSE06 functional and machine learning prediction. The values of the complex dielectric constant and the refractive index of all phases of the CsSnI₃ were determined.

Effective sports training should be attuned to the athlete's specific conditionings and characteristics. In motor learning research, two often neglected factors that influence this resonance are the learner's athletic background and the structural diversity of exercises (e.g., relative similarity). This study examines the effects of three learning approaches (i.e., contextual interference (CI), differential learning (DL), and free-play control condition (CO)) on the parallel learning of Handball (HB), Volleyball (VB), and Basketball (BB) skills, considering participants' prior sport backgrounds. Forty-five males (15 HB, 15 VB, and 15 BB players) with a mean age of 22±1.4 years and at least 6 years of experience in the mastered discipline voluntarily participated in this study. A pre-post-retention test design including a 6-week-intervention program was employed. In terms of short-term (pre-post) gain, only the DL- group significantly improved their performance in both non-mastered disciplines (p=0.03 for the BB free-throw and p=0.05 for the HB shooting tests), with a trend (ES=0.53) towards an improvement in the performance of the mastered VB underarm-pass skill. In terms of relatively permanent gains, the CI group significantly improved their performances from pre- to retention-test only in the non-mastered BB free-throw skill (p=0.018). In contrast, the DL group significantly improved their performance at retention compared to the pre-test in both non-mastered BB (p=0.004) and HB (p=0.003) skills, with a trend (ES=0.4) towards improvement in the mastered VB test. In both short, and relatively permanent terms, higher composite score gains were observed in DL compared to CI (p=0.001 and 0.002) and CO (p=0.001 and <0.0001). In conclusion, the present findings provide additional support for the potential advantages of the DL model over those of CI. These findings can serve as the basis for tailored training and intervention strategies and provide a new perspective for addressing various issues related to individual and situational learning.

Dacomitinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor indicated for the treatment of patients with advanced non-small cell lung cancer (NSCLC) and EGFR-activating mutations. Proton pump inhibitors decreased dacomitinib exposure. This anal-ysis summarizes the effect of H2RA on dacomitinib exposure. A within-patient comparison of steady-state trough concentrations (Ctrough,ss) of dacomitinib and its active metabolite and active moiety with and without concomitant use of H2RA was conducted using a linear mixed effects model with pooled data from 11 clinical studies in patients with NSCLC. An oral absorption PBPK model was constructed and verified using clinical PK data after a single dose of dacomitinib in healthy volunteers to estimate the effect of gastric pH altered by an H2RA on dacomitinib PK. The adjusted geometric mean of dacomitinib Ctrough,ss of dacomitinib parent, metabolite and active moiety following co-administration with H2RA was approximately 86%, 104% and 100% relative to that following dacomitinib 45 mg administration without H2RA (P>0.05). The PBPK modeling showed negligible change in dacomitinib Cmax and AUC over 0-24 hours after H2RA administra-tion, when compared with those administered dacomitinib alone. Co-administration of an H2RA with dacomitinib is not expected to have any clinically relevant effect on dacomitinib exposure.

In the seasonally frozen regions, during the grouting of prestressed bridge ducts in low-temperature environments, incompletely cured grout materials undergo volumetric changes due to the freeze-thaw cycling, resulting in structural cracks along the prestressing ducts of the bridge, thereby diminishing the bridge's operational lifespan. To investigate the frost heaving characteristics of grout materials under freeze-thaw cycles and propose potential enhancements, this study was devised to conduct frost heaving stress tests on grout materials. Through this research, we gained insights into how various additives affect the frost heaving stress characteristics of grout materials under freeze-thaw cycles. Incorporating analyses of free water content, setting time, compressive strength, as well as macroscopic examinations such as XRD and SEM, this study delves into the mechanisms for enhancing frost heaving characteristics of grout materials. Furthermore, it proposes a research approach that utilizes multiple admixtures to improve the frost heaving properties of grout materials. Through frost heaving stress tests and other macroscopic experiments, the study investigates the influence of these combined admixtures on frost heaving stress in grout materials and elucidates the underlying improvement mechanisms. The results indicate that reducing the water-cement ratio, incorporating calcium formate, sulfoaluminate cement, air-entraining agents, and carbamide all have a positive impact on mitigating frost heaving stress in grout materials. However, the improvement mechanisms differ, and employing a single measure alone is insufficient to effectively reduce frost heaving stress while meeting performance criteria such as compressive strength, setting time, and flowability. Free water content emerges as a crucial indicator determining the magnitude of frost heaving stress in grout materials, with 11.5% of free water content representing the critical threshold for frost heaving in grout materials. Utilizing composite admixtures can simultaneously decrease free water content, lower the freezing point of free water, and alleviate frost heaving deformation, resulting in more efficient reduction of frost heaving stress. When the admixture content reaches 9.9%, frost heaving stress is eliminated, and the comprehensive performance parameters including compressive strength, setting time, and flowability meet the specified requirements.

This research investigates the utilization of human driving models in autonomous vehicles, particularly in scenarios with minimal or no interactions with other vehicles. Human driving models provide valuable insights into driver behavior and play a crucial role in shaping the behavior of autonomous vehicles, enhancing their performance and user experience. The primary focus of the study is the creation of a planning model for autonomous vehicles when navigating roundabouts in the absence of traffic. This model seeks to emulate human driving behavior, ensuring predictability, safety, optimization of traffic flow, and adaptation to various roundabout geometries. To achieve this, the research introduces a trajectory model that takes into account geometric attributes and speed variations within roundabouts. The model is calibrated using empirical data and generalizes parameters through statistical regression methodologies. This model is referred to as "MRoundabout" and is evaluated for its consistency in generating plans that closely mimic human driving behavior within roundabouts. While the study presents a promising approach, it acknowledges limitations related to the model's reliance on geometric attributes and its inability to account for external factors like weather conditions. This research underscores the importance of bridging the gap between theoretical research and practical application, with the aim of enhancing safety and the overall user experience in real-world driving scenarios.

Familial Exudative Vitreoretinopathy (FEVR), Norrie disease, and persistent fetal vascular syndrome (PFVS) are extremely rare retinopathies that are clinically distinct but are unified by abnormal retinal endothelial cell function – and subsequent irregular retinal vascular development and/or aberrant inner blood-retinal-barrier (iBRB) function. The early angiogenesis of the retina and its iBRB is a delicate process that is mediated by the canonical Norrin Wnt-signaling pathway in retinal endothelial cells. Pathogenic variants in genes that play key roles within this pathway such as NDP, FZD4, TSPAN12, and LRP5, have been associated with the incidence of these retinal diseases. Recent efforts to further elucidate the etiology of these conditions have not only highlighted their multigenic nature but have also resulted in the discovery of pathological variants in additional genes such as CTNNB1, KIF11, and ZNF408, some of which operate outside of the Norrin Wnt-signaling pathway. Recent discoveries of FEVR-linked variants in two other Catenin genes (CTNND1, CTNNA1) and the Endoplasmic Reticulum Membrane Complex Subunit-1 gene (EMC1) suggest that we will continue to find additional genes that impact the neural retinal vasculature, especially in multi-syndromic conditions. The goals of this review are to briefly highlight the current understanding of the roles of their encoded proteins in retinal endothelial cells to understand the essential functional mechanisms that can be altered to cause these very rare pediatric retinal vascular diseases.

Understanding the dynamic interaction between piles and surrounding soil under vehicular impacts is essential for effectively designing and optimizing soil-embedded vehicle barrier systems. The complex behavior of pile-soil systems under impact loading, attributed to the soil’s nonlinear behavior and large deformation experienced by both components, presents significant simulation challenges. Popular computation techniques, such as the Updated Lagrangian Finite Element Method (UL-FEM), encounter difficulties in scenarios marked by large soil deformation, e.g., impacts involving rigid piles. While mesh-free particle and discrete element methods offer another option, their computational demands for field-scale pile-soil impact simulations are considerable. We introduce the erosion method to bridge this gap by integrating UL-FEM with an erosion algorithm designed for simulating large soil deformations during vehicular impacts. Validation against established physical impact tests confirmed the method’s effectiveness for flexible and rigid pile failure mechanisms. Additionally, this method was used to investigate the effects of soil mesh density, soil domain sizes, and boundary conditions on the dynamic impact response of pile-soil systems. Our findings provide guidelines for optimal soil domain size, mesh density, and boundary conditions. This investigation sets the stage for improved, computationally efficient techniques for the pile-soil impact problem, leading to better pile designs for vehicular impacts.

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

BiFeO3/La0.7Sr0.3MnO3 (BFO/LSMO) epitaxial heterostructures were successfully synthesized by pulsed laser deposition on (001)-oriented SrTiO3 single crystal substrates with Au top electrodes. Stable bipolar resistive switching characteristics regulated by ferroelectric polarization reversal was observed in the Au/BFO/LSMO heterostructures. The conduction mechanism was revealed to follow the Schottky emission model, and the Schottky barriers in high resistance and low resistance states were estimated based on temperature-dependent current–voltage curves. Further, the observed memristive behavior was interpreted via the modulation effect on the depletion region width and the Schottky barrier height caused by ferroelectric polarization reversal, combining with the oxygen vacancies migration near the BFO/LSMO interface.

We presents results obtained from the numerical simulation of the gas-phase chemical kinetics in atmospheric pressure air non-equilibrium plasmas. In particular we have addressed the effect of pulsed operation mode of a planar dielectric barrier discharge. As it was conjectured, the large difference in the time scales involved in the fast dissociation of molecules in plasmas and their subsequent reactions to produce stable chemical species, makes the presence of a continuously repeated plasma production stage unnecessary and a waste of electrical power and efficiency. Results on NOx remediation, ozone production, water vapor and ammonia dissociation are discussed. A few comparisons with experimental findings in a dielectric barrier discharge reactor already used for applications is briefly addressed too. Our results clearly indicate a pattern for the optimization of the discharge using a carefully designed repetition rate and duty-cycle.

This article presents the possibilities of using ferrite absorption material for shielding rooms with medical devices in order to additionally protect them against the limits of the electric component of the E field, which are up to 61 V/m. These values may appear in connection with the currently launched 5G system operating in the high-band frequency range, i.e. 28 GHz and 38 GHz, and may cause negative effects on the operation of medical devices. The possibilities of using ferrite absorption material for shielding rooms with medical devices were determined based on the results of measurements of the electrical properties of the ferrite material performed using two methods: the reflection method and the free space method. In the article, the complex electrical permittivity and complex magnetic permeability were determined for a ferrite plate based on measurements of the reflection coefficient and the transmission (attenuation) coefficient. The presented calculation and measurement results were used to show the properties of the ferrite material in the frequency range from 15 GHz to 45 GHz and to show the possibility of using it for shielding rooms as a material absorbing electromagnetic waves in this frequency range.

Compared to tin lead alloys, lead-free tin alloys have lower toxicity, making them more widely used. In this study, Sn-20Bi-0.3Al-xY solders alloys were prepared. The effects of the addition of Y on its microstructure, micro-hardness, wettability and mechanical properties was investigated. The result showed that the addition of Y had significant effect on the refinement of Sn-20Bi-0.3Al-xY. From the spreading tests results, Y increased the wettability of the solders, however when the fraction of Y gradually increased, the wettability reduced. The ultimate tensile and hardness of Sn-20Bi-0.3Al-xY solders alloys were increased as the content of Y increasing.

Modern imaging strategies are paramount to studying living systems such as cells, bacteria, and fungi and their response to pathogens, toxicants, and nanomaterials as modulated by exposure and environmental factors. The need to understand the processes and mechanisms of damage, healing and cell survivability of living systems continues to motivate the development of alternative imaging strategies. Of particular interest is the use of label-free techniques that minimize interference of biological processes by foreign marking substances and reduce intense light exposure and potential photo-toxicity effects. This review focus on the potential synergic capabilities of atomic force microscopy (AFM) as a well-developed and robust imaging strategy with demonstrated applications to unravel intimate details in biomedical applications, with the label-free, fast, and enduring Holotomographic Microscopy (HT) strategy. We first review the operating principles that form the basis for the complementary details provided by these techniques regarding the surface and internal information provided by HT and AFM is essential and complimentary for the development of several biomedical areas studying the interaction mechanisms of nanomaterials with living organisms. First, AFM can provide superb resolution on surface morphology and biomechanical characterization. Second, the quantitative phase capabilities of HT enable superb modeling and quantification of the volume, surface area, protein content, and mass density of the main components of cells and microorganisms, including morphology of cells in microbiological systems. These capabilities result from directly quantifying refractive index changes without requiring fluorescent markers or chemicals. As such, HT is ideally suited for long-term monitoring of living organisms in conditions close to their natural settings. We present a case-based review of the principal uses of both techniques and their essential contributions to nanomedicine and nanotoxicology, emphasizing cancer and infectious disease control. The synergic impact of the sequential use of these complementary strategies provides a clear drive for adopting these techniques as interdependent fundamental tools.

Extracellular vesicles (EVs), including exosomes, microvesicles, and other lipid vesicles derived from cells, play a pivotal role in intercellular communication by transferring information between cells. EVs secreted by progenitor and stem cells have been associated with the therapeutic effects observed in cell-based therapies, and they also contribute to tissue regeneration following injury, such as in orthopedic surgery cases. This review briefly explores the involvement of EVs in tissue repair and nerve regeneration, their potential as drug carriers, and their significance in stem cell research and cell-based therapies. It underscores the importance for bioengineers to comprehend and manipulate EV activity to optimize the efficacy of tissue engineering and regenerative therapies.

While it is well known that 98-99% of the human genome do not encode proteins, but are nevertheless transcriptionally active and give rise to a broad spectrum of noncoding RNAs (ncRNAs) with complex regulatory and structural functions, specific functions have so far been assigned to only a tiny fraction of all known transcripts. On the other hand, the striking observation of an overwhelmingly growing fraction of ncRNAs, in contrast to an only modest increase in the number of protein-coding genes, during evolution from simple organisms to humans, strongly suggests critical but so far essentially unexplored roles of the noncoding genome for human health and disease pathogenesis. Research into the vast realm of the noncoding genome during the past decades thus lead to a profoundly enhanced appreciation of the multi-level complexity of the human genome. Here, we address a few of the many huge remaining knowledge gaps and consider some newly emerging questions and concepts of research. We attempt to provide an up-to-date assessment of recent insights obtained by molecular and cell biological methods, and by the application of systems biology approaches. Specifically, we discuss current data regarding two questions: (1) By which mechanisms could evolutionary recent ncRNAs with critical regulatory functions in a broad spectrum of cell types (neural, immune, cardiovascular) constitute novel thera-peutic targets in human diseases ? (2) Since noncoding genome evolution is causally linked to brain evolution, and given the pro-found interactions between brain and immune system, could human-specific brain-expressed ncRNAs play a direct or indirect (immune-mediated) role in human diseases? Synergistic with the remarkable recent progress regarding delivery, efficacy, and safety of nu-cleic acid-based therapies, the ongoing large-scale exploration of the noncoding genome for human-specific therapeutic targets is encouraging to proceed with the development and clinical evaluation of novel therapeutic pathways suggested by these research fields.

Objectives: This study aimed to assess the impact of a predictive model for detecting extracapsular extension on pathology (pECE+) on biochemical recurrence-free survival (BCRFS) within 4 years after robotic-assisted radical prostatectomy (RARP). Methods: Retrospective data analysis from a single center between 2015 to 2022. Variables under consideration included prostate-specific antigen (PSA) levels, patient age, prostate volume, MRI semantic features and Gleason score (GS). We also assessed the influence of pECE+ and positive surgical margins on BCRFS. using the Kaplan-Meier survival function and Cox regression model were assessed. Additionally, we analyzed the MRI features on BCR (biochemical recurrence) in low/intermediate risk patients. Results: 177 participants with a follow-up exceeding 6 months post-RARP were included. The 1-year, 2-year, and 4-year risks of BCR after curative prostatectomy were 5%, 13%, and 21%, respectively. The survival analysis showed that adverse MRI features as macroscopic ECE on MRI (mECE+), capsular disruption, high tumor capsular contact length (TCCL), GS≥8, positive surgical margins (PSM), and pECE+ on pathology were risk factors for BCR. In low/intermediate-risk patients (pECE- and GS &lt;(4+4)) the presence of adverse MRI features, has been shown to increase the risk of BCR. Conclusions: The study highlights the importance of incorporating predictive MRI features for detecting extracapsular extension pre-surgery in influencing early outcomes and clinical decision-making; mECE+, TCCL, capsular disruption, and GS≥8 based on pre-surgical biopsy were independent prognostic factors for early BCR. The presence of adverse features on MRI can assist in identifying low/intermediate-risk patients who would benefit from closer monitoring.

Background: Glioblastoma is the most common primary brain neoplasm in adults, with still a poor prognosis despite a constant effort to improve patients’ survival. Some neuroradiological volumetric parameters seem to play a predictive role on Overall Survival (OS) and Progression Free Survival (PFS). The aim of this study is to analyze the impact that the volumetric areas of contrast-enhancing tumor and perineoplastic edema have on survival of patients treated for glioblastoma; Methods: A series of 87 patients who underwent surgery was retrospectively analyzed; OS and PFS were considered as the end points of the study. For each patient a multidisciplinary revision was conducted in collaboration with the Neuroradiology and Neuro-Oncology board. A manual and semi-automatic measurement were adopted to perform the radiological evaluation: contrast Enhancement Preoperative (CE-PTV) and Postoperative Tumor Volume (CE-RTV), Edema/Infiltration Preoperative (T2/FLAIR-PV) and Postoperative Volume (T2/FLAIR-RV); necrosis volume inside the tumor (NV); total tumor volume, including necrosis (TV); Results: The median OS value was 9 months and the median PFS value was 4 m; the mean values were respectively 12,3 m and 6,9 m. Multivariate analysis showed that the OS related factors were: adjuvant chemo-radiotherapy (p &lt; 0,0001), CE-PTV &lt; 15 cm³ (p=0,03), surgical resection &gt; 95% (p=0,004) and the presence of a “pseudo-capsulated” radiological morphology (p=0,04); Conclusions: maximal safe resection is one of the most relevant predictive factors for patients’ survival. The semi-automatic pre-operative MRI evaluation could play a key role in prognostically categorizing these tumors.

Device-mediated, non-invasive drug delivery across the blood-brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is a tightly packed layer of endothelial cells that shields the brain from harmful substances in the blood, allowing necessary nutrients to pass through. It is a highly selective barrier, which poses a challenge to delivering therapeutic agents into the brain. Several non-invasive techniques and devices have been proposed or investigated to enhance drug delivery across the BBB. This paper presents the current state of the art and case studies that address the pharmacology, technology, delivery systems, regulatory approval, ethical concerns, and future possibilities.

Trans-arterial radioembolization (TARE) is a form of radiation therapy performed for hepatocellular carcinoma (HCC) via selective intra-arterial injection of Yttrium-90 loaded microspheres. This was a multicenter retrospective study of consecutive patients with HCC who underwent TARE between July 2009 and May 2019. Using pre-treatment computed tomography imaging, the total cross-sectional area (cm2) of the abdominal skeletal muscle at the third lumbar vertebra was measured. The skeletal muscle index (SMI) was calculated by normalizing the muscle area to patient height. In total, 347 patients (median age, 65 years; 284 male) were included in the study. A total of 108 (31.1%) patients had portal vein tumor thrombus (PVTT) and 126 (36.3%) were classified as sarcopenic. The median overall survival (OS) was 28.1 months (95% CI, 24.8-35.7) and median progression-free survival was 8.0 months (95% CI, 6.4-9.4). Multivariate Cox regression analysis revealed that sarcopenia (hazard ratio [HR], 1.36; 95% CI, 1.00-1.85, p = 0.05), PVTT (HR, 1.82; 95% CI, 1.33-2.49, p &lt; 0.01), alpha-fetoprotein (AFP) (≥200 ng/mL) (HR 1.41; 95% CI, 1.04-1.92, p = 0.03), and albumin-bilirubin grade (2-3) (HR 1.74; 95% CI, 1.24-2.43, p &lt; 0.01) were independently associated with poor OS. TARE provided favorable long-term outcomes for patients with advanced HCC. Pre-treatment sarcopenia independently associated with survival, suggesting its utility as a surrogate biomarker for identifying TARE candidates.

The blood-brain barrier (BBB) acts as a specialized structure separating the brain from peripheral blood circulation and plays an important role in brain function. Following an ischaemic stroke or cerebral ischaemia, the BBB is damaged leading to degraded proteins being released into blood circulation. However, little is known about cerebral ischaemia and reperfusion (I/R) induced BBB damage and changes in circulatory biomarkers. This study aims to use both immunohistochemistry and western blotting (WB) to examine neuronal death, glial cell alterations and changes in BBB tight junction (TJ) proteins such as zonula occludens-1 (ZO-1), Occludin and Claudin-5 in the hippocampus in a murine model of cerebral I/R. The changes in these proteins in the blood serum of this model were assessed by enzyme-linked immunosorbent assay. The results showed neuronal death and a significant increase in glial fibrillary acidic protein (GFAP), a protein primarily expressed in astrocytes and a significant decrease in TJ proteins, ZO-1, Occludin and Claudin-5 in the hippocampus of occluded mice as compared to sham-operated mice. These changes are associated with an increased level of these proteins in blood serum in ischaemic mice, suggesting that these proteins can be used as potential biomarkers for determining ischaemic stroke.

Alzheimer’s disease (AD) and vascular dementia (VaD) together contribute to almost 90% of all dementia cases leading to major health challenges of our time with a substantial global socioeconomic burden. While in Alzheimer’s disease, the improved understanding of Amyloid beta (Aß) mismetabolism and tau hyperphosphorylation as pathophysiological hallmarks has led to significant clinical breakthroughs, similar advances in VaD are lacking. We thus highlight here the importance of shared pathomechanisms found in AD and VaD: Endothelial damage, blood brain barrier (BBB) breakdown and hypoperfusion inducing oxidative stress, inflammation and demyelination and thus trophic uncoupling in the neurovascular unit. A dysfunctional endothelium and BBB lead to the accumulation of neurotoxic molecules and Aß through impaired clearance, which in turn leads to neurodegeneration. In this context we discuss possible neuropathological parameters, which might serve as biomarkers and thus improve diagnostic accuracy or reveal targets for novel therapeutic strategies for both forms of dementia.

Determination of the fetal gender in the first trimester is important in twin pregnancy cases of familial X-linked genetic syndromes and helps determine chorionicity. We assessed and compared the accuracy of first-trimester ultrasound scans, and circulating cell-free fetal DNA (cffDNA) performed by non-invasive prenatal screening (NIPS) in determining fetal gender in the first trimester of twin pregnancies. For this purpose, we enrolled prospectively pregnant women with twin during the first trimester, gestational week (GA) 11-13. The fetal gender was determined using both ultrasound scans and cffDNA screening. Both results were compared to the newborn gender at delivery. A total of 113 women with twin pregnancies were enrolled. There was 100% sensitivity and specificity in Y chromosome detection using cffDNA. The accuracy of gender assignment using ultrasound in any first-trimester scans was 79.7%. Accuracy level increased from 54.2% in CRL 45-54 mm to 87.7% in CRL 55-67 mm and 91.5% in CRL 67-87 mm. Male fetuses had significantly higher chances of a gender assignment error compared to female fetuses, odds ratio = 23.57 (CI 7.356 - 75.66). This is the first study that compared the accuracy of gender determination in the first trimester by cffDNA and by ultrasound scanning in twin pregnancy. It was concluded that the cffDNA is highly sensitive and specific in determining the presence of the Y chromosome in twin pregnancies in the first trimester. Between CRL 67-87 mm, ultrasound scanning offers a highly accurate determination of fetal gender in twin pregnancies. Larger cohorts of multi-center studies are warranted.

The amino acids (AAs) and vitamins imbalances are observed in celiac disease (CD). This study evaluated the plasma profile of vitamin A and AAs and the expression level of IL-2, IL-4, IL-10, IL-12 and TGFβ in CD patients. A total of 60 children and adults with CD and 40 healthy controls (HCs) were included. Plasma profile of Vitamin A and AAs and the mRNA expression levels of target genes were assessed. Active adult patients exhibited a decrease in Vitamin A levels (p=0.04) and an increase in IL-2 (p=0.008) and IL-12 (p=0.007) mRNA expression compared to HCs. Treated adult patients showed elevated Serine (p=0.003) and Glycin (p=0.04) levels, as well as increased IL-12 (P&lt;0.0001) mRNA expression, and a decrease in Tryptophan (p=0.04) levels relative to the controls. Additionally, treated adult patients had higher plasma levels of Threonine compared to both active (p=0.04) and control (p=0.02) subjects, and increased mRNA expression of IL-4 (p=0.01) in comparison to active patients. In active children with CD, IL-2 mRNA level was found to be higher than in controls (P&lt;0.0001) and in treated children (p=0.005). Treated children with CD exhibited decreased plasma levels of Tryptophan (p=0.01) and Isoleucine (p=0.01) relative to the controls, and increased mRNA expression of TGFβ (p=0.04) relative to active patients. Managing Retinoic acid levels is crucial to alleviate intestinal inflammation of CD patients. Threonine, tryptophan, and Isoleucine are potential therapeutic options for treating CD, and targeting serine, histidine, tyrosine, and aspartate may hold promise as therapeutic targets for CD patients.

Rollover prevention of partially-filled tank trucks is an industry teaser, with the core challenge being real-time perception and observation of the liquid state inside the tank. In order realize re-liable observation of sloshing liquid, this article firstly proposes a sloshing modeling method based on multi-degree-of-freedom pendulum model, and derives the double mass trammel pendulum model (DMTP, 2DOF) accordingly, which accurately reflects the sloshing dynamics under more pervasive working conditions. Secondly, a free surface fluctuation sensor is designed based on magnetostriction, capable of measuring the inclination and height of the liquid level inside tanks filled with hazardous chemical. Finally, the unscented Kalman filter (UKF) is utilized to synthesize the information of the two, establishing a credible real-time observation of the sloshing liquid. Verified through vehicle-fluid coupled co-simulation, under condition of con-secutive double lane change, observation error of the proposed method is only 25.9% that of the open-loop calculation, providing a secure guarantee for the observation of the state variables of the single pendulum model (SP) used for most kinds of anti-rollover controller.

Abstract: The ever-increasing use of motor vehicles causes a number of traffic safety and community issues, which are particularly severe in cities, accompanied with scarcity of parking spaces and challenges encountered in the road layout alteration projects. The commonly applied solutions include designation of through streets and implementation of on-street parking on residential streets and retrofitted traffic calming measures (TCMs). This article presents the results of the study conducted on a two-way street where Metered Parking System MPS was implemented together with diagonal and parallel parking spaces, refuge islands, horizontal deflection and lane narrowing by a single-sided chicane. The aim of this study was to identify those TCMs that effectively helped to reduce the island approach speed. Heuristic method was applied to assess the effect of the respective TCMs on reducing the island approach speed and the key speed reduction determinants were defined using cause and effect diagram and Pareto chart. Comparative analyses were carried out to rate the respective TCMs as effective, moderately effective or ineffective. Section 1 of this article presents the output of the literature review on urban parking analyses and TCM efficacy. Section 2 presents the study site and the applied heuristic method. The study results are presented in Section 3. Section 3 defines the determinants on the cause and effect diagram and analyses the determinants using the Pareto chart. The final conclusions and comments are given in Section 5. Although the study was limited to a single street in Poland, the findings may hold true in other countries where similar TCMs are used.

The necessity to reduce the effect of the greenhouse phenomenon imposed the turn of the food packaging technology to the use of biobased raw materials decreasing the carbon dioxide fingerprint. In this direction alginates derived from brown algae species are of the most promising biobased biopolymers, used for development of edible active coatings, capable to protect food from oxidation/bacterial spoilage. In this study sodium alginate, which was plasticized with glycerol and mixed with a biobased thymol/natural halloysite nanohybrid, was used to develop novel edible active coatings. Active nanocomposite coatings developed by mixing of pure halloysite with sodium alginate/glycerol matrix were produced for comparison purposes. X-Ray and Fourier Transform Infrared Spectroscopy indicated higher compatibility of thymol/halloysite nanohybrid with sodium alginate/glycerol matrix compared to the relevant of pure halloysite. This increased compatibility led to higher tensile properties, water/oxygen barrier properties, and total antioxidant activity. All coating samples were applied as edible active coatings for “tsalafouti” spreadable soft cheese, exhibited a reduction of mesophilic microbial population of more than one log10(cfu/g) unit comparing with uncoated cheese. Moreover, the reduction of mesophilic microbial population was increased by increasing halloysite and thymol content which indicates the sodium alginate/glycerol/thymol/halloysite as promising edible active coatings for “tsalafouti”.

Plastic materials have revolutionized modern life, particularly in the domain of food packaging, owing to their versatility, lightweight nature, and ease of processing. However, the environmental ramifications of non-degradable plastics have raised concerns. Polylactic acid (PLA), derived from renewable sources, presents a sustainable alternative due to its biodegradability and exceptional barrier, mechanical, and safety properties. Nevertheless, the high UV transmittance of PLA limits its use for photosensitive food and pharmaceutical packaging, where UV radiation can lead to nutritional loss and spoilage. Various methods have been explored to enhance the UV-blocking capabilities of PLA, including the integration of inorganic nanoparticles and surface coatings. Despite advancements, these approaches often compromise the inherent transparency of PLA. Incorporating large conjugated groups can maintain transparency but introduces additional challenges. This paper reviews modification methods to enhance PLA's UV-barrier properties and anticipates its expanded utility in food and drug packaging, promoting UV resistance and diversifying PLA's applications.

The unsupervised domain-adaptive vehicle reidentification approach aims to transfer knowledge from a labeled source domain to an unlabeled target domain, however there are knowledge differences between the target domain and the source domain. To reduce domain differences, existing unsupervised domain-adaptive rerecognition methods generally require access to the source domain data to assist in re-training the target domain model. But for security reasons, in many cases, data between different domains cannot communicate. To this end, this paper proposes an unsupervised domain-adaptive vehicle re-identification method based on source-free knowledge transfer. First, by constructing a passive domain knowledge migration module, the target domain is consistent with the source domain model output to train a generator to generate the "source-like samples". Then, it can effectively reduce the model knowledge difference and improve the model generalization performance. According to the experiment and testing of VeRi776 and VehicleID, two mainstream public data sets in this field, the rank-k and mAP indexes obtained are both improved, and are suitable for object re-recognition tasks without source data.

In this paper, we present an innovative technique that improves the convergence order of iterative schemes that do not require the evaluation of Jacobian matrices. Using this procedure, we achieve a remarkable increase in the order of convergence, raising it from p to p + 3 units, which results in a remarkable improvement in the overall performance. We have conducted comprehensive numerical tests in various scenarios to validate the theoretical results, showing the efficiency and effectiveness of the new Jacobian-free schemes.

In Philadelphia chromosome positive B-cell (Ph+) acute lymphoblastic leukemia (LLA), growing evidence has ac-cumulated about the efficacy of low-intensity and chemo-free regimens. Our objective was to analyze all recent trials evaluating these treatments and to compare them in terms of efficacy. We applied the Shiny method, an artificial intelligence technique, to analyze Kaplan-Meier curves and reconstruct patient-level data. Reconstructed patient data were then evaluated through standard survival statistics and subjected to indirect head-to-head treatment comparisons. The endpoint was progression-free survival (PFS). Based on 848 reconstructed patients, 9 trials were analyzed. The survival data from these trials were pooled into three types of treatments: i) treatments based on ty-rosine kinase inhibitors (TKIs) combined with reduced-intensity chemotherapy (denoted as TKICHE); ii) TKIs as-sociated to steroids with no chemotherapy (TKISTE); iii) chemotherapy-free combinations of blinatumomab plus TKIs (TKIBLI). According to the Shiny method, the three PFS curves were reported in a single Kaplan-Meier graph and subjected to survival statistics. In terms of PFS, TKIBLI ranked first, TKICHE second, and TKISTE third; the differences between these three regimens were statistically significant. This multi-treatment Kaplan-Meier graph, generated through the Shiny method, summarized the current evidence on these treatments in both qualitative and quantitative terms.

Neuroinflammation is considered to be a significant component in a range of neuropathologies. Unfortunately, whilst its role is well recognized, the options for therapeutic intervention are limited. As such, there is a need to identify novel targets in order to increase treatment options. Given its role as both a neurotransmitter and an immune modulator, substance P and its NK1 receptor have been widely studied as a potential therapeutic target. There is evidence that NK1 receptor antagonists may exert beneficial effects in a range of conditions, including traumatic brain injury and stroke. Blocking the NK1 receptor has been shown to reduce blood-brain barrier dysfunction, reduce cerebral oedema, and reduce the levels of pro-inflammatory cytokines. These actions are associated with improved survival and functional outcomes. The NK1 receptor has also been shown to be involved in the inflammatory reaction to CNS infection, and hence antagonist may have some benefit in reducing infection-driven inflammation. However, the NK1 receptor may also play a role in the host immune response to infection, and so here, the potential beneficial and detrimental effects need to be carefully balanced. As such, the purpose of this review is to provide a summary of the involvement of substance P in acute inflammation, particularly in the context of traumatic brain injury and stroke.

In the framework of mean field approximation, we consider a spin system consisting of two interacting sub-ensembles: spins interactions with in each sub-ensemble are ferromagnetic, while the inter-ensemble interactions are antiferromagnetic. We define the effective number of the nearest neighbors, and show that if the two sub-ensembles have the same effective number of the nearest neighbors, the classical form of critical exponents (, , , ) gives way to the non-classical form (, , , ), and the scaling function changes simultaneously. We demonstrate that this system allows for two second-order phase transitions and two first-order phase transitions. We observe that an external magnetic field does not destroy the phase transitions, but only shifts their critical points, allowing for control of the system’s parameters. We discuss the regime when the magnetization as a function of the magnetic field develops a low-magnetization plateau, and show that the height of this plateau abruptly rises to the value of one when the magnetic field reaches a critical value. Our analytical results are supported by a Monte Carlo simulation of a three-dimensional layered model.

The laser sintering process and modification of electrophoretic deposition (EPD) YSZ coatings on YSZ air plasma sprayed thermal barrier coatings (TBCs) were investigated. Ni-based superalloy was plasma sprayed using yttria-stabilized zirconia (YSZ) to perform thermal barrier coating with 400 μm thickness. The electrophoretic deposition (EPD) technique was used for depositing nanopowder of YSZ on the surface of YSZ TBCs. In this study, a technology of direct sintering the green EPD layer by laser beam was carried out. The best conditions of deposition YSZ overlay coating using DC current were obtained with applied voltage 40 V, deposition time 5 min, and suspension concentration 10 g/l. Iodine was added to the solutions as the stabilizing agent. To overcome the disadvantages of high sintering temperatures, laser sintering was taken as a new approach. Microstructures for all specimens were studied using Field Emission Scanning Electron Microscopy (FESEM) with EDS analysis. Surface roughness was investigated using AFM analysis and central line average (CLA). The results indicated that the morphology after the direct laser sintering of the EPD layer has a fine and controllable grain size, high hardness, and low roughness. Which is better than the direct laser on plasma-sprayed coatings.

Considering the aging society and budget constraints, a strategy for reforming public transportation welfare policies is essential for sustainability. Among the various transportation welfare policies, fare discount policies are provided to specific age groups, and most countries offer benefits to several public transportation. South Korea provides a fare-free policy limited to subways, and the need for policy modification is emerging due to sustainability problems caused by an aging society. Hence, the scope of the policy should be expanded to all travel modes, but the discount rate should be reduced, or the target group should be reduced in consideration of the budget. This study proposes a travel mode to focus on by city through the preference of the elderly. The latent class model is employed to classfy stated preference data collected from the survey. The estimation results show a significant preference heterogeneity depending on the level of subway supply by region, and a policy focused on subways would be more reasonable in cities with sufficient subway infrastructure. Hence, regarding sustainability, it may be more appropriate to focus on specific means than to provide the same discount policy for all public transport.

Background: Metastatic oral squamous cell carcinoma (OSCC) is associated with poor patient prognosis. Metastasis is a complex process involving various proteins, tumor cell alterations including changes caused by the epithelial-to-mesenchymal transition (EMT) process, and interactions with the tumor microenvironment (TME). In this study, we investigate a combined protein marker system consisting of connexin 43 (Cx43), EMMPRIN (CD147), E-cadherin and vimentin during the invasive metastatic process of OSCC and the possibility of using this system for prognosis prediction. Methods: The protein expression profiles of Cx43, EMMPRIN, E-cadherin and vimentin were investigated by immunohistochemistry in tissue samples from 24 OSCC patients. The metastatic process was mapped through different regions of interest (ROI) of adjacent healthy oral mucosa (OM), center of primary OSCC, invasive front (IF), and local cervical lymph node metastases (LNM). Disease-free survival (DFS) and overall survival (OS) were the primary clinical endpoints. Results: Significant changes in the expression profiles of the different marker proteins were detected between the different ROIs (all p values &lt; 0.05). Multivariable Cox regression analysis revealed a significant effect of increased EMMPRIN expression towards IF on DFS (p = 0.019) and OS (p = 0.023). The combined predictive analysis showed a significant predictive value of the marker system for DFS (p = 0.0017) and OS (p = 0.00044). Conclusions: The combined marker system was able to significantly predict patient prognosis. An increase in EMMPRIN expression towards IF showed the strongest effect and could be an interesting new antimetastatic therapy approach.

Andrographis paniculata leaves have been widely used in traditional medicine due to their rich content of phenolic compounds. In this study, we evaluated the total phenolic and flavonoid content of Andrographis paniculata leaf extracts (ALE), as well as its antioxidant activities against DPPH, ABTS, and hydrogen peroxide radicals. Additionally, we conducted cell viability assays, RT-PCR, and western blot analysis to investigate the biochemical effects of ALE on UVB-induced HaCaT cells. Our results revealed that ALE exhibited a high concentration of polyphenols and flavonoids, which were associated with potent abiotic antioxidant properties. Furthermore, ALE treatment effectively abrogated the damage caused by UVB radiation on key molecules such as hyaluronan synthase 1, Aquaporin 3, and loricrin in HaCaT cells. ALE also demonstrated the ability to reduce the overactivation of mitogen-activated protein kinases (MAPKs) and the expression of pro-inflammatory cytokines, including interleukin-6 and interleukin-1β in UVB-induced HaCaT cells. Additionally, ALE positively influenced the peroxisome proliferator-activated receptor alpha in these cells. Overall, our findings highlight the antioxidant and anti-inflammatory effects of ALE, as well as its significant role in modulating skin barrier functions. These results contribute to the growing body of evidence supporting the therapeutic potential of ALE in skincare and dermatological applications.

Background and Objectives: C-arm free MIS techniques can offer significantly reduced rates of postoperative complications such as blood loss and hospitalization time. Another advantageous long-term aspect is the notably diminished exposure to radiation which is known to cause ma-lignant changes. This study emphasizes that, in some cases of spinal conditions which require a procedural intervention, C-arm free MIS techniques hold stronger indications than open surgeries guided by image intensifier. Materials and Methods: In this research, a retrospective analysis and review of various cervical and thoracic spinal procedures, performed in our hospital, by applying C-arm free techniques. The course of the study explains the basic steps of the procedures and demonstrating postoperative or intra-operative results. For anterior cervical surgery, we performed OPLL resection, while for posterior cervical surgery, we performed posterior fossa decompression for Chiari malformation, minimally invasive cervi-cal pedicle screw fixation (MICEPS) and modified Goel technique with C1 lateral mass screw for atlantoaxial subluxation. Re-garding the thoracic spine, we performed anterior correction for Lenke type 5 scoliosis, and transdiscal screw fixation for DISH fractures. Results: C-arm free techniques are safe procedures that offer precise and high-quality postoperative results by offering sufficient spine alignment and adequate decompression depending on the case. Blood loss, postoperative pain and wound infection are other important aspects of spine surgery that must be always taken into consideration. Conclusions: Navigated C-arm free techniques are safe and precise procedures implemented in the treatment of surgically demanding conditions. They can significantly increase accuracy while decreasing the operative time. They represent the advancement in the field spine surgery and are hailed as the future of the same

Photosystem II (PSII) is a quinone-utilising photosynthetic system that converts light energy into chemical energy and catalyses the splitting of water. PsbA (D1) and PsbD (D2) are the core subunits of the reaction centre that provide most of the ligands to the redox-active cofactors and exhibit photooxidoreductase activities that convert quinone and water into quinol and oxygen. This analysis explored the putative uncoupled electron transfer pathways surrounding P680+ induced by far-red light (FRL) based on photosystem II (PSII) complexes containing substituted D1 subunits in Halomicronema hongdechloris. Chlorophyll f-synthase (ChlF) is a D1 protein paralog. Modelling PSII-ChlF complexes determined several key protein motifs of ChlF. The PSII complexes showed a dysfunctional Mn4CaO5 cluster if ChlF replaced the D1 protein. We propose the mechanism of chlorophyll f synthesis from chlorophyll a via free radical chemistry in an oxygenated environment created by over-excited pheophytin a and an inactive water splitting reaction due to an uncoupled Mn4CaO5 cluster in PSII-ChlF complexes. The role of ChlF in the formation of an inactive PSII reaction centre is under debate and the putative mechanisms of chlorophyll biosynthesis are discussed.

Maxillary sinus augmentation with a lateral approach (MSA) is a well-established treatment. In this prospective study, we evaluated risk factors for postoperative bone-graft displacement and report the clinical application of long-term resorbable GMEM-B-2 (L-lactic acid/-caprolactone [P(LA/CL)]) as a barrier membrane to cover the open window in the lateral wall in MSA. Twenty-four patients underwent MSA according to the relevant criteria; CT data obtained before and 1 week (1W) and 5–6 months (5M) post-MSA, bone height changes, bone height reduction rates at 1W and 5M post-MSA, bone-graft displacement measurements, and risk factors were examined. All patients showed bone height increments (p &lt; 0.005). However, no difference was observed between 1W and 5M post-MSA. Bone-graft displacement was observed in eight patients; the reduction rate from 1W to 5M post-MSA was 8.38% ± 4.88%. Sex, septa, maxillary sinus floor–palatal bone distance, and maxillary sinus floor–natural mouth distance were associated with bone-graft displacement (p &lt; 0.05). Height from the maxillary sinus floor to the palatal bone and the sinus angle influenced the augmentation amount (p &lt; 0.05). The L-lactic acid/ε-caprolactone [P(LA/CL)] membrane compared favourably with other membranes and may be useful as a barrier membrane for the MSA open window.

This research evaluated the role and feasibility of the granular nanocellulose particles (GNC) from sugarcane bagasse obtained from enzymatic hydrolysis in reducing lipid digestibility and permeability in the in vitro simulated gastrointestinal (GI) system. GNC concentration (0.02%, w/v) had significantly affected the released free fatty acid (FFA) reduction of approximately 20%. The Pick-ring emulsion of the GNC and olive oil simulation mixture revealed higher oil droplet size distribution and stability in the initial stage than the vortexed mixture formation. The difference in particle size distribution and zeta potential of the ingested GNC suspension and GNC-olive oil emulsion were displayed during the in vitro gastrointestinal simulation. GNC particles interacted and distributed surrounding the oil droplet leading to the interfacial emulsion. The GNC concentration (0.01-0.10%, w/v) showed low toxicity on the HIEC-6 cell, ranging from 80.0 to 99% of cell viability. The release of FFA containing the ingested GNC suspension and GNC-olive oil emulsion was about 30% reduction compared to without GNC digest solution. The FFA and triglyceride permeability through the HIEC-6 intestinal epithelium monolayer were deceased in the digesta containing the ingested GNC and emulsion. This work indicated that GNC represented a significantly critical role and properties in the GI tract and reduced lipid digestion and absorption. This GNC could be utilized as an alternative food additive or supplement in fatty food for weight control due to their inhibiting lipid digestibility and assimilation.

Wastewater contaminated with antibiotics is a major environmental challenge. We developed here the green synthesis of bio-graphenes by using natural precursors (Xanthan, Chitosan, Boswellia, Tragacanth). The use of these precursors can act as templates to create 3D doped graphene structures with special morphology. Also, this method is a simple method for in-situ synthesis of doped graphenes. The elements present in the natural polymers (N) and other elements in the natural composition (P, S) are easily placed in the graphene structure and improve the catalytic activity due to the structural defects, surface charges, increased electron transfers, and the high absorption. In this mechanism, O2 dissolved in water absorbs onto the positive charged C in doped graphenes to create oxygenated radicals, which enables the degradation of antibiotic molecules. Light irradiation increases the amounts of radicals and rate of antibiotic removal. The results have shown that the hollow cubic Chitosan-derived graphene has shown the best performance due to the doping of N, S, and P. The Boswellia-derived grapheme shows the highest surface area, but lower catalytic performance, which indicates the more effective role of doping in the catalytic activity. The effect of oxygen and light were also studied to accelerate the degradation process.

A scalable optical convolutional neural network (SOCNN) based on free-space optics and Koehler illumination was proposed to address the limitations of the previous 4f correlator system. Unlike Abbe illumination, Koehler illumination provides more uniform illumination and reduces crosstalk. SOCNN allows for scaling up of the input array and the use of incoherent light sources. Hence, the problems associated with 4f correlator systems can be avoided. We analyzed the limitations in scaling the kernel size and parallel throughput and found that SOCNN can offer a multilayer convolutional neural network with massive optical parallelism.

The acetylcholinesterase-inhibitory potential of the oleanane-type triterpenes and their glycosides from the Terminalia arjuna (Combreatceae) bark, i.e. arjunic acid, arjunolic acid, arjungenin, arjunglucoside I, sericic acid, and arjunetin, is presented. The studies are based on the in silico pharmacokinetic and biomimetic studies, the acetylcholinesterase (AChE) inhibitory activity tests, and the molecular docking research. Based on the calculated pharmacokinetic parameters, arjunetin and arjunglucoside I are indicated as able to cross the blood-brain barrier. The compounds of interest exhibit marked acetylcholinesterase inhibitory potential, which was tested in the TLC bioautography test. The longest time to reach brain equilibrium is observed for both the arjunic and arjunolic acids and the shortest one for arjunetin. All compounds exhibit high and relatively similar magnitude of binding energies, varying from ca. -15 to -13 kcal/mol. The superposition of the most favorable positions of all ligands interacting with AChE is analyzed. The correlation between the experimentally determined IC50 values and the steric parameters of the molecules is investigated. The inhibition of the enzyme by the analyzed compounds shows their potential to be used as cognition enhancing agents. For the most potent compound (arjunglucoside I; ARG), the kinetics of AChE inhibition is tested. The Michaelis–Menten constant (Km) for the hydrolysis of the acetylthiocholine iodide substrate was calculated to be 0.011 mM.

Astragaloside IV (AIV) – triterpenoid saponin from the Astragalus mongholicus roots with the proved acetylcholinesterase (AChE)-inhibitory capability was used as the substance with the potential to attenuate memory impairment. Scopolamine (SCOP), antagonist of muscarinic cholinergic receptors and lipopolysaccharide (LPS), neuroinflammation inducer were used to impair memory processes in the passive avoidance (PA) test in mice. This memory impairment in the SCOP-treated mice was attenuated by the earlier intraperitoneal (ip) administration of AIV in the dose of 25 mg/kg. The reduction of memory impairment by LPS was not observed, therefore AIV does not reverse memory impairments through the anti-inflammatory mechanisms. All the studied doses of AIV did not affect basic locomotor activity of mice. As a result of the post-mortem analysis of mice body tissues, the largest content of AIV was determined in the kidneys, then in the spleen, liver and the smallest one in brain by mass spectrometry.

Abstract: The brain endothelial cell (BEC) glycocalyx (ecGCx) is a BEC surface coating consisting of a complex interwoven polysaccharide (sweet husk) mesh-like network of membrane-bound proteoglycans, glycoproteins, and glycosaminoglycans (GAGs) covering the apical luminal layer of the brain endothelial cells. The ecGCx may considered as the 1st barrier of a tripartite blood-brain barrier (BBB) consisting of 1) ecGCx; 2) BECs; (3) extravascular compartment of pericytes, extracellular matrix, and perivascular astrocytes, Perturbations of this barrier allow for increased permeability in the postcapillary venule that will be permissive to both fluids, solutes, and proinflammatory peripherally-derived leukocytes into the perivascular spaces (PVS) to result in enlargement as well as increased neuroinflammation. The ecGCx is known to have multiple functions, which include its physical and charge barrier, mechanical transduction, regulation of vascular permeability, modulation of inflammatory response, and anticoagulation functions. This review discusses each of the listed functions in detail and utilizes multiple transmission electron micrographs and illustrations to allow for a better understanding of the ecGCx structural and functional roles as it relates to enlarged perivascular spaces (EPVS). This is the 5th review of a series quintet that discuss the importance of EPVS from the perspective of the cells of brain barriers. Attenuation and/or loss of the ecGCx results in brain barrier disruption with increased permeability to proinflammatory leukocytes, fluids and solutes, which accumulate in the postcapillary venule perivascular spaces. This accumulation results in obstruction and results in EPVS with impaired waste removal of the recently recognized glymphatic system. Importantly, EPVS are progressively being regarded as a marker of cerebrovascular and neurodegenerative pathology.

In this paper, we consider the one-dimensional Ising model (shortly, 1D-MSIM) having mixed spin-(s,(2t−1)/2) with nearest neighbors and the external magnetic field. We establish the partition function of the model by means of the transfer matrix. Under a null boundary condition, we compute certain thermodynamic quantities for the 1D-MSIM. We find some precise formulas to determine the model’s free energy, entropy, magnetization, and susceptibility. By examining the model’s associated iterative equations, we use the cavity approach to investigate the phase transition problem. We numerically determine the model’s periodicity.

Barrier coverage is a fundamental application in wireless sensor networks, which is widely used to protect a region through intruder detection for smart city. In this paper, we study a new branch of barrier coverage, named warning barrier coverage (WBC). Different from the classic barrier coverage, WBC has the inverse protect direction, which protects unexpected visitors by warning them away from the region enclosed by sensor barriers. The WBC holds a promising prospect in many danger keep out applications for smart city. For example, a WBC can enclose the debris area in the sea and alarm any approaching ships in order to avoid their damaging propellers. One special feature of WBC is that the target region is usually dangerous and its boundary is previously unknown. Hence, the scattered mobile nodes need to detect the boundary and form the barrier coverage themselves. It is challenging to form these distributed sensor nodes into a barrier because a node can sense only the local information and there is no global information of the unknown region or other nodes. To this end, we propose a novel solution AutoBar for mobile sensor nodes to automatically form a WBC for smart city. To pursue the high coverage quality, we theoretically derive the optimal distribution pattern of sensor nodes using convex theory. Based on the analysis, we design a fully distributed algorithm that enables nodes to collaboratively move towards the optimal distribution pattern. In addition, AutoBar is able to reorganize the barrier even any node is broken. To validate the feasibility of AutoBar, we develop the prototype of the specialized mobile node, which consists of two kinds of sensors: one for boundary detection and another for visitor detection. Based on the prototype, we conduct extensive real trace driven simulations in various smart city scenarios. Performance results demonstrate that AutoBar outperforms the existing barrier coverage strategies in terms of coverage quality, formation duration, and communication overhead.

The notion of quantum-mechanics-free subsystem (QMFS) was introduced by Tsang and Caves in 2012. They showed that it is possible to design the dynamics of coupled quantum systems in such a way that one can construct a subsystem in which a given classical dynamics is realized, thus avoiding the measurement back-action of quantum mechanics. Although they mention that the Heisenberg picture equations of motion for QMFS was first proposed by Koopman in 1931 as a formulation of classical Hamiltonian dynamics in Hilbert space, in fact the connection between QMFS and Koopmann-von Neumann mechanics is deeper. Namely, quantum-mechanics-free subsystem is nothing but the realization of Sudarshan's perspective on the Koopman-von Neumann mechanics.

Parametric form findings of free-form space structures and qualitative assessment of their aesthetics are among the concerns of architects. This study aims to evaluate the aesthetic aspect of these structures using ML algorithms based on the expert's experiences. First, various datasets of forms were produced using a parametric algorithm of free-form space structures written in Grasshopper. Then, three multilayer perceptron ANN models were adjusted in their most optimal modes using the results of the preference test based on the aesthetic criteria including simplicity, complexity, and practicality. The results indicate that the ANN models can quantitatively evaluate the aesthetic value of free-form space structures.

Most of the current methods for stabilizing electric arc furnace (EAF) slag are time-consuming and cannot be completely stabilized. In view of this, this study aimed to apply microbial‑induced calcium carbonate precipitation (MICP) technology in the stabilization of EAF reducing slag, and this was to be achieved by using the reaction between carbonate ions and free calcium oxide (f-CaO) in reducing slag to form a more stable calcium carbonate to achieve the purpose of stabilization. The test results showed that, when the EAF reducing slag aggregates (ERSAs) were immersed in Bacillus pasteurii bacteria solution or water, the f-CaO contained in it would react such that stabilization was achieved. The titration test results showed that the f-CaO content of the ERSAs immersed in the bacterial solution and water decreased. The expansion test results of the ERSAs that were subjected to hydration showed that the seven-day expansion of ERSAs after biomineralization could meet the Taiwan regulation requirement of a less than 0.5% expansion rate. The thermogravimetric analysis showed that both the experimental group and the control group might contain calcium carbonate compounds. The results of the X-ray diffraction analysis showed that the CaCO3 content in the ERSAs that were immersed in the bacterial solution was significantly higher than those that were immersed in water. Moreover, the compressive strength test results of concrete prepared with ERSAs showed that the compressive strength of the control group concrete began to decline after 28 days. In contrast, the experimental group concrete had a good stabilization effect, and there was no decline in compressive strength until the age of 180 days. At the age of 240 days, the surface cracks of the experimental group were particularly small, while the surface of the control group showed obvious cracks. These results confirmed that a mineralization reaction with B. pasteurii bacteria could be used as a stabilization technology for ERSAs.

Oriented object detection is a challenging task in scene text detection and remote sensing image analysis, which has attracted extensive attention in recent years with the development of deep learning. Currently, mainstream oriented object detectors are based on preset anchor boxes. This method increases the computational load of the network and cause a large amount of anchor box redundancy. To solve this problem, we propose anchor-free oriented object detection based on the Gaussian centerness(AOGC), a single-stage anchor-free detection method. Our method uses contextual attention FPN(CAFPN) to obtain the contextual information of the target. Then we design a label assignment method for oriented objects. Finally, we develop a Gaussian kernel-based centerness branch, which can effectively determine the significance of different anchors. AOGC achieves mAP of 74.30% on the DOTA-1.0 datasets and 89.80% on the HRSC2016 datasets, respectively. AOGC exhibits superior performance to other methods in oriented anchor-free object detection methods.

G-protein-coupled receptors (GPCRs) are ubiquitous sensors and regulators of cellular functions. Each GPCR exists in complex aggregates with multiple resting and active conformations. Designed to detect weak stimuli, GPCRs can also activate spontaneously, resulting in basal ligand-free signaling. Agonists trigger a cascade of events leading to an activate agonist-receptor-G protein complex with high agonist affinity. However, the ensuing signaling process can further remodel the receptor complex to reduce agonist affinity, causing rapid ligand dissociation. The acutely activated ligand-free receptor can continue signaling, as proposed for rhodopsin and  opioid receptors, resulting in robust receptor activation at low agonist occupancy with enhanced agonist potency. Continued receptor stimulation can further modify the receptor complex, regulating sustained ligand-free signaling - proposed to play a role in opioid dependence. Basal, acutely agonist-triggered, and sustained elevated ligand-free signaling could each have distinct functions, reflecting multi-state conformations of GPCRs. This review addresses basal and stimulus-activated ligand-free signaling, its regulation, genetic factors, and pharmacological implications, focusing on opioid and serotonin receptors, and the growth hormone secretagogue receptor (GHSR). Ligand-free signaling of intracellular 5-HT2A receptors could mediate therapeutic effects of psychedelic drugs. Research avenues are suggested to close gaps in our knowledge of ligand-free GPCR signaling.

In recent years, there has been a notable rise in the incidence of breast cancer among young patients, who exhibit worse survival outcomes and distinct characteristics compared to the intermediate and elder patients. Therefore, it’s imperative to identify identify the specific features unique to young patients, which could offer insights into potential therapeutic strategies and improving survival outcomes. In our study, we performed an integrative analysis of bulk transcriptional and genomic data from extensive clinical cohorts to identify prognostic factors. Additionally, we analyzed the single-cell transcriptional data and conducted in vitro experiments. Our work confirmed that young patients exhibited higher grading, worse disease-free survival (DFS), a higher frequency of mutations in TP53 and BRCA1, a lower frequency of mutations in PIK3CA, and upregulation of eight metabolic pathways. Notably, galactose metabolism pathway showed upregulation in young patients and was associated with worse DFS. Further analysis and experiments indicated that galactose metabolism pathway may regulate the stemness of cancer cells and ultimately contribute to worse survival outcomes. In summary, our finding identified distinct clinicopathological, transcriptional, and genomics features and revealed a correlation between galactose metabolism pathway, stemness, and poor disease-free survival of breast cancer in young patients.

In recent years, the number of open preservation surgeries for treatment of laryngeal Cancer has increased. The purpose of this surgery is to avoid the highly mutilating intervention of a total laryngectomy (TL) and to maintain laryngeal function while ensuring oncological radicality. The aim of this study was to assess the oncologic results of OPHL I and II and to identify prognostic factors that could impact patient survival and local failure rates. This study was conducted on 182 patients with laryngeal squamous cell carcinoma treated with OPHLs between 2005 and 2015. The survival rates of a group of patients treated with TL between 2004 and 2014 were taken into con-sideration to compare survival outcomes. The DSS in pT2 and pT3 tumors in relation to the type of surgery showed no statistically significant difference between OPHLs and TL (p=0.54 and p=0.63 respectively). The 5-years T-recurrence free survival showed that pT4 tumors, perineural/vascular positive invasion and OPHL IIb + ARY treated tumors were associated with a higher risk of tumor recurrence (p<0.0001, p=0.0005 and p=0.016 respectively). OPHLs represent an excellent alterna-tive to TL considering the characteristics of the tumor and the general conditions of the patient.

Neurodegenerative diseases encompass a broad spectrum of profoundly disabling disorders that impact millions of individuals globally. While their underlying causes and pathophysiol-ogy display considerable diversity and remain incompletely understood, a mounting body of evidence indicates that the disruption of blood-brain barrier (BBB) permeability, resulting in brain damage and neuroinflammation, constitutes a shared characteristic among them. Con-sequently, targeting the BBB has emerged as an innovative therapeutic strategy for address-ing neurological diseases. Within this review, we not only explore the neuroprotective, neu-rotrophic, and immunomodulatory benefits of mesenchymal stem cells (MSCs) in combating neurodegeneration but also delve into their recent role in modulating the BBB. We will delve into the cellular and molecular mechanisms through which MSC treatment impacts primary age-related neurological disorders like Alzheimer’s disease, Parkinson’s disease, and stroke as well as immune-mediated conditions such as multiple sclerosis. Our focus will center on how MSCs participate in the modulation of cell transporters, matrix remodeling, stabilization of cell-junction components, and restoration of BBB network integrity in these pathological con-texts.

This work introduces a novel numerical method designed to address three-dimensional unsteady free surface flows incorporating integral viscoelastic constitutive equations, specifically, the K-BKZ-PSM (Kaye–Bernstein, Kearsley, Zapas - Papanastasiou, Scriven, Macosko) model. The new proposed methodology employs a second-order finite difference approach along with the deformation fields method to solve the integral constitutive equation, and the marker-particle method (known as \emph{Marker-and-Cell}) to accurately capture the evolution of the fluid's free surface. The newly developed numerical method has proven its effectiveness in handling complex fluid flow scenarios, including confined flows and extrudate swell simulations of Boger fluids. Furthermore, a new semi-analytical solution for velocity and stress fields is derived, considering fully developed flows of a K-BKZ-PSM fluid in a pipe.

Roller milling of sorghum and quinoa seeds into flour fractions (course, middle, and fine) was investigated, chemically analysed and applied in the baking of gluten-free sourdough bread. Gap settings were adjusted to 0, 5, 8 and 10 for quinoa and 3, 5, and 7 for sorghum. The fine fractions reached values of up to about 41% (gap 8) for quinoa and around 20% for sorghum (gap 5). SEM pictographs illustrated clear separation of each fraction with chemical analysis showing high contents of protein, TDF (total dietary fibre) and IDF (insoluble dietary fibre) in the course fraction. Up to 77% starch content was obtained in the fine fraction with significant amounts of SDF (soluble dietary fibre) which has good health benefits. Increasing the dough moisture up to 90% helped in decreasing the bread crumb firmness, while low Avrami parameters and RVA pasting behaviour indicated slow bread staling rate for both sourdough breads.

One-Dimensional Solar Cell Capacitance Simulator (1D-SCAPS) and n-i-p planar configuration have been employed for the simulation of the caesium tin iodide (CsSnI₃)-based perovskite solar cell (PSC) with titanium (IV) oxide (TiO₂) and copper thiocyanate (CuSCN) as the electron and hole transport materials respectively. The results obtained for the initially modeled PSC compared well with similar devices in the literature but marred with high recombination rate. As such, the defect density in the CsSnI₃ absorber was varied from 10¹³ cm^-3 to 10¹⁷ cm^-3 and enriched with SnCl₂ (additive) and Br⁻(dopant) respectively. This strategy ensured a reduced concentration of Sn⁴⁺ vacancy (V_Sn) in the CsSnI₃ absorber with improved carrier lifetime and diffusion length beyond 0.05 ns and 1.1µm by a magnitude of the order of 10³ and 10² respectively for the enriched CsSnI₃ –based PSC. For the optimized PSC, we recorded V_OC=1.289 V, J_SC=32.60 mA.cm^-2, FF=83.56% and PCE=35.12%.

Objective: To evaluate the effect of care bundles on treatment compliance and intestinal barrier function in patients with refractory septic shock in the intensive care units (ICUs). Methods: In this retrospective study, the clinical data of 94 patients with refractory septic shock admitted to our hospital between June 2020 and April 2022 were collected. Patients with routine nursing were included in the routine group, and those with care bundles were assigned to the care bundles group, with 47 cases in each group. Outcome measures included nursing efficiency, treatment compliance, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE II) score, intestinal barrier function, inflammation factor level, treatment outcome and complications. Results: Care bundles resulted in significantly higher nursing efficiency and treatment compliance versus routine care (P<0.05). Patients receiving care bundles showed significantly higher SOFA scores and APACHE II scores than those receiving routine care (P<0.05). Intestinal fatty-acid binding protein (I-FABP), diamine oxidase (DAO), lactate, endotoxin, and intestinal dysfunction scores in the care bundles group were significantly lower than those in the conventional group after treatment (P<0.05). Care bundles were associated with significantly lower levels of procalcitonin (PCT) and hypersensitive C-reactive protein (hsCRP), shorter time to symptom relief, ICU treatment time, and duration of mechanical ventilation, and lower 28-d morbidity and mortality versus routine care (P<0.05). Patients in the care bundles group had a significantly lower incidence of complications than those in the routine group (P<0.05). Conclusion: Care bundles effectively enhance treatment compliance, improve intestinal barrier function and treatment outcomes, reduce the inflammatory response, and decrease the risk of SOFA score, APACHE II score, and complications in patients with refractory septic shock.

Various vestibuloplasty techniques have been reported to increase the attached mucosa (AM) and vestibular depth around dental implants. However, these surgical methods have disadvantages, such as limitations in manipulation, necessity of suturing, postoperative discomfort, swelling, and pain. This study aimed to evaluate the efficacy of laser-assisted periosteal fenestration (LA-PF) in treating a patient with a shallow vestibule and insufficient AM around dental implants. The LA-PF technique was performed using an Er:YAG laser. First, a partial-thickness apically positioned flap (APF) was performed. Horizontal periosteal fenestration was performed using an Er:YAG laser to expose the bones. Periosteal suturing was not required. After 12 months, sufficient AM and deepened vestibule were obtained and maintained. Thus, the LA-PF technique may be a simple and predictable treatment modality for vestibuloplasty around dental implants.

There exists a variety of studies about tumor-infiltrating lymphocytes (TILs) in cervical cancer, but their prognostic value in correlation to the histopathological subtype was never investigated. Therefore, the aim of this study was to quantify TILs in a panel of 250 sporadic cervical cancers and investigate the correlation with cervical cancer subtype and patient survival. TIL levels were significantly increased in the subgroup of squamous cell carcinomas in comparison to adenocarcinomas. In squamous cell carcinomas, TIL infiltration shows a negative correlation to age, FIGO stage and to the histone protein modification H3K4me3. Moreover, in adenocarcinomas, it was positively correlated to p16 and to the glucocorticoid receptor and inversely correlated to the MDM2 protein and to H3K4me3. Interestingly, immune infiltration was an independent positive prognosticator for disease free survival (DFS) in patients with squamous cell carcinomas, those bearing tumors with the strongest TIL infiltration showing the better DFS. Altogether, the present study provides a differentiated overview of the relations between TIL levels and prognosis in patients with cervix squamous cell carcinomas vs patients with cervix adenocarcinomas.

Proteins in biological systems function at the interface of single molecule and bulk chemistry and thus provide novel insights into the basic physical chemistry of scaling and emergent phenomena. For example, a binary mechanical model based on the chemistry of muscle contraction unifies molecular mechanics and thermodynamics and provides an explicit solution to the Gibbs paradox. Using the same model system, here I show that chemical activities of molecular states have no effect on chemical kinetics or energetics. Specifically, while the concentration or number of molecules in a molecular state is widely thought to contribute to reaction free energies, here I show that it is not the physical presence of molecules that pushes a reaction forward but the number of microstates, , accessible in a chemical state that pulls a reaction toward equilibrium with an entropic force down an entropic funnel. With the derivation of an entropic contribution to chemical kinetics, I develop a novel chemical kinetic formulation that fully describes the chemical thermodynamics of both equilibrium and non-equilibrium reactions in terms of an a priori system reaction energy landscape.

Objective: To evaluate the effect of care bundles on treatment compliance and intestinal barrier function in patients with refractory septic shock in the intensive care units (ICUs). Methods: In this retrospective study, the clinical data of 94 patients with refractory septic shock admitted to our hospital between June 2020 and April 2022 were collected. Patients with routine nursing were included in the routine group, and those with care bundles were assigned to the care bundles group, with 47 cases in each group. Outcome measures included nursing efficiency, treatment compliance, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE II) score, intestinal barrier function, inflammation factor level, treatment outcome and complications. Results: Care bundles resulted in significantly higher nursing efficiency and treatment compliance versus routine care (P<0.05). Patients receiving care bundles showed significantly higher SOFA scores and APACHE II scores than those receiving routine care (P<0.05). Intestinal fatty-acid binding protein (I-FABP), diamine oxidase (DAO), lactate, endotoxin, and intestinal dysfunction scores in the care bundles group were significantly lower than those in the conventional group after treatment (P<0.05). Care bundles were associated with significantly lower levels of procalcitonin (PCT) and hypersensitive C-reactive protein (hsCRP), shorter time to symptom relief, ICU treatment time, and duration of mechanical ventilation, and lower 28-d morbidity and mortality versus routine care (P<0.05). Patients in the care bundles group had a significantly lower incidence of complications than those in the routine group (P<0.05). Conclusion: Care bundles effectively enhance treatment compliance, improve intestinal barrier function and treatment outcomes, reduce the inflammatory response, and decrease the risk of SOFA score, APACHE II score, and complications in patients with refractory septic shock.

This study aimed to compare the prognosis and characteristics of patients with advanced hepatocellular carcinoma treated with first-line atezolizumab plus bevacizumab (AB) combination therapy and hepatic artery infusion chemotherapy (HAIC). We retrospectively assessed 179 and 72 patients treated with HAIC and AB combination therapy, respectively, between January 2018 and January 2023. The progression-free survival of patients treated with HAIC was significantly superior than that of patients treated with AB (P&lt;0.05), but there was no significant difference in overall survival and objective response rate (ORR) between the two groups (P=0.1056 and P=0.137, respectively). After propensity score matching (PSM), our data revealed that there was no significant difference in PFS between patients who received AB combination therapy and HAIC therapy (P=0.8888). However, patients who received AB combination therapy had significantly better overall survival than those who received HAIC therapy (P=0.0133). In addition, after PSM, significant differences in ORR and disease control rate were not observed. In conclusion, our propensity score study reveals that patients treated with AB therapy have a significantly longer OS than those treated with HAIC.

One of the hallmarks of microgravity-induced effects in several cellular models is represented by the alteration of oxidative balance with the consequent accumulation of Reactive Oxygen Species (ROS). It is well known that male germ cells are sensitive to oxidative stress and to changes of gravitational force even if published data on germ cell models are scarce. To gain more insights into the mechanisms of male germ cell response to altered gravity, a 3D cell culture model has been established from TCam-2 cells, a seminoma-derived cell line considered the only human cell line available to study in vitro mitotically active human male germ cells. TCam-2 cell spheroids were cultured for 24 hours under unitary gravity (Ctr) or simulated microgravity (s-microgravity) conditions, these last ones were obtained using the Random Positioning Machine (RPM). A significant increase in intracellular ROS and mitochondria superoxide anion levels has been observed after RPM exposure. In line with these results a trend of protein and lipid oxidation increase, and increased pCAMKII expression levels were observed after RPM exposure. The ultrastructural analysis by Transmission Electron Microscopy revealed that RPM-exposed mitochondria appeared enlarged and, even if seldom, disrupted. Notably, even the expression of the main enzymes involved in the redox homeostasis appears modulated by RPM exposure in a compensatory way, being GPX1, NCF1, and CYBB downregulated, whereas NOX4 and HMOX1 upregulated. Interestingly, HMOX1 is involved in the heme catabolism of mitochondria cytochromes, and therefore the positive modulation of this marker can be associated to the observed mitochondria alteration. All together, these data demonstrate TCam-2 spheroid sensitivity to acute SM exposure and indicate the capability of these cells to trigger compensatory mechanisms that allow to overcome the exposure to altered gravitational force.

A two-layer Fe-Cr-Al-Zr surface alloy was synthesized on a zirconium substrate by magnetron sputtering and subsequent low-energy high-current electron-beam (LEHCEB) processing. Thicknesses of the top Fe69Cr20Al11 (at.%) relatively large-grained (~1 µm) and transition Fe-Zr Cr-Al amorphous layers were about 0.7 and 0.6 µm, respectively. In turn, the amorphous layer consisted of two Fe64–54Zr8–22Cr21–17Al8–7 and Fe40–16Zr42–78Cr12–4Al6–2 (at.%) sublayers, differing in both zirconium and iron concentrations in wide ranges, which were separated by another nanocrystalline interlayer. The Fe-Cr-Al-Zr surface alloy serve as a diffusion barrier, preventing interaction of the zirconium substrate with oxygen from an environment. It was thermally stable up to ≈1173 K.

A topical challenge for algorithms in general and for automatic image categorization and generation in particular is presented with the aim of highlighting strengths and deficiencies of current Artificial Intelligence approaches while sketching a way forward. A general lack of encompassing symbol-embedding and (not only) -grounding in some bodily basis is made responsible for current deficiencies. A concomitant dearth of hierarchical organization of concepts follows suite. As a remedy for these shortcomings, it is proposed to take a wide step back and to newly incorporate aspects of cybernetics and analog control processes. It is claimed that a promising overarching perspective is provided by the Ouroboros Model with a valid and versatile algorithmic backbone for general cognition at all accessible levels of abstraction and capabilities.

Abstract: Filipendula ulmaria, commonly known as meadowsweet, is a wild herbaceous flowering plant widely distributed in Europe. A range of salicylic acid derivatives and flavonol glycosides have been previously associated with the antirheumatic and diuretic properties of F. ulmaria. In the present work, an hydroalcoholic extract of F. ulmaria aerial parts was extensively profiled using an efficient NMR-based dereplication strategy. The approach involves fractionation of the crude extract by centrifugal partition chromatography (CPC), ¹³C NMR analysis of the fractions, 2D-cluster mapping of the whole NMR dataset and finally, structure elucidation using a natural metabolite database, validated by 2D NMR data interpretation and liquid chromatography coupled to mass spectrometry. The chemodiversity of the aerial parts was quite broad, with 28 compounds unambiguously identified, belonging to various biosynthetic classes. The F.ulmaria extract and CPC fractions were screened for their potential to improve skin epidermal barrier function and also skin renewal properties using in vitro assays performed on Normal Human Epidermal Keratinocytes. Fractions containing quercetin, kaempferol glycosides, ursolic acid, pomolic acid, naringenin, β-sitosterol, and tellimagrandins I and II were found to be responsible for the up-regulation of genes related to skin barrier function, epidermal renewal and stress responses. This research is significant as it could provide a natural solution for improving hydration and skin renewal properties.

: In Philadelphia chromosome positive B-cell (Ph+) acute lymphoblastic leukemia (LLA), growing evidence has accumulated about the efficacy of low-intensity and chemo-free regimens. Our objective was to analyse all recent trials evaluating these treatments and to compare them in terms of efficacy. We applied the Shiny method, an artificial intelligence technique, to analyse Kaplan-Meier curves and reconstruct patient-level data. Reconstructed patient data were then evaluated through standard survival statistics and subjected to indirect head-to-head treatment comparisons. The endpoint was progression-free survival (PFS). Based on 562 reconstructed patients, 8 trials were analyzed. The survival data from these trials were pooled into three types of treatment: i) treatments based on tyrosine kinase inhibitors (TKIs) combined with reduced-intensity chemotherapy (denoted as TKICHE); ii) TKIs associated to steroids with no chemotherapy (TKISTE); iii) chemotherapy-free combinations of blinatumomab plus TKIs (TKIBLI). According to the Shiny method, the three PFS curves were reported in a single Kaplan-Meier graph and subjected to survival statistics. In terms of PFS, TKIBLI ranked first, TKICHE second, and TKISTE third; the differences between these three regimens were statistically significant. In conclusion, the multi-treatment Kaplan-Meier graph generated in this study has effectively summarized the current evidence on these treatments in comparative terms.

Caries are lesions caused by acidic compounds derived from the metabolism of bacteria such as streptococci. It is not merely the presence of acidogenic bacteria that causes caries but an imbalance in the oral biofilm microhabitat and its behavior. One factor underlying biofilm formation is quorum sensing (QS), that in gram-positives relies on peptidic molecules, whereas in gram-negatives is driven by small diffusible signals. Strategies based on QS inhibition have been proposed as alter-natives to antimicrobial therapies. Here, we investigate the antibiofilm potential of the lactonase enzyme Aii20J, previously reported as effective against biofilms of periodontal disease origin. We generated in vitro polymicrobial biofilms dominated by gram-positive taxa using supragingival samples from caries-free and caries-active children. The effect of Aii20J on the biofilms was evalu-ated regarding its biomass-reducing ability, as assessed with crystal violet assay, and its effects on the bacterial composition of the polymicrobial biofilms, as assessed by 16S community profiling. We describe significant biomass reductions upon Aii20J exposure without significant changes in bac-terial composition at the genus level. Our results support the use of Aii20J to prevent oral biofilm formation while highlighting the influence of the polymicrobial environment on bacterial commu-nities and their response to antibiofilm treatments.

Uzbekistan, as an emerging national economy, aims to attract foreign direct investment (FDI) to foster the development of its free economic zones (FEZs). While recent policy reforms have enhanced the country's appeal to investors and facilitated the inflow of international capital, challenges persist in attracting investment. This study employs an economic geographical approach to analyze and propose solutions to these obstacles. By examining the spatial patterns of FEZs and FDI through a comprehensive geographical lens, this research utilizes document analysis as an alternative to empirical analysis, considering the broader context rather than focusing on a specific FEZ. The findings reveal that the insufficiency of an innovation-driven environment, logistical systems, energy resource-related issues, among others, negatively impact the inflow of FDI into FEZs. Moreover, the study underscores the significance of economic geography in understanding these factors. Finally, relevant insights and recommendations are provided from an economic geographical perspective.

The Baltic Sea coast is one of the geographical areas of Europe most threatened by the current climate change. This issue concerns erosional processes, groundwater flows affecting sea-shore settings. Long term hydrological investigations within the western sector of the Łeba Barrier, northern Poland, based on a network of monitoring stations, coupled with the meteorology records of the past 12 years, revealed significant fluctuations in ground water fluxes from the Baltic Sea on the adjoining mainland. Groundwater resources are negatively affected by sea-level drops in the coastal areas along the southern Baltic coast. The low sea levels strengthen the effects of low precipitation and high temperatures, causing altogether the occurrence of hydrogeological drought in the coastal sandbar areas. Drought periods are characterized by lowering of water-tables in the Slowinski National Park. The obtained results have direct relevance to a long-term assessment of water resources, environmental protection of the climatically most susceptible ecosystems, as well as the tourism management of this popular visitors’ destination.

Coffee is not only a delicious beverage but also an important dietary source of natural antioxidants. We live in an oxidative world where it is impossible to avoid pollution, stress, food additives, radiation, and other sources of oxidants that eventually lead to severe health disorders. Fortunately, there are chemicals in our diet that counteract the hazards posed by the reactive species that trigger oxidative stress. They are usually referred to as antioxidants; some of them can be versatile compounds that exert such a role in various ways. This review summarizes, from a chemical point of view, the antioxidant effects of relevant molecules found in coffee. Their ways of action and trends in activity are analyzed, considering the data gathered so far from both theory and experiments. The influence of the media and pH in aqueous solution, and structure-activity relationships are discussed. The protective role of the explored compounds is examined. A particular section is devoted to derivatives of some coffee components, and another one to their bioactivity. The data used in the analysis come from theoretical anc computational protocols, which have been proven to be very usefull in this context. Hopefully, the information provided here will promote further investigations into the amazing chemistry contained in our morning cup.

Given the accelerating scientific, clinical and consumer interest in highly-prevalent functional gastrointestinal disorders, appropriate therapeutic strategies are needed to address the many aspects of digestive dysfunction. Accumulating evidence for the crucifer-derived bioactive molecule, sulforaphane in upstream cellular defence mechanisms highlights its potential as a therapeutic candidate in targeting functional gastrointestinal conditions together with systemic disorders. This article catalogues the evolution of and rationale for a hypothesis that utilises multifunctional sulforaphane as the initial step in restoring the ecology of the gut ecosystem; it does this primarily by targeting the functions of intestinal epithelial cells. A growing body of work has identified the colonocyte as the driver of dysbiosis, so that targeting gut epithelial function could provide an alternative to targeting the microbes themselves for remediation of microbial dysbiosis. The hypothesis discussed herein has evolved over several years and is supported by case studies showing the application of sulforaphane in gastrointestinal disorders, related food intolerance and several systemic conditions. To our knowledge, this is the first time the effects of sulforaphane have been reported in a clinical environment where several of its key properties within the gut ecosystem appear to be related to its nutrigenomic effects on gene expression.

Coffee is not only a delicious beverage but also an important dietary source of natural antioxidants. We live in an oxidative world where it is impossible to avoid pollution, stress, food additives, radiation, and other sources of oxidants that eventually lead to severe health disorders. Fortunately, there are chemicals in our diet that counteract the hazards posed by the reactive species that trigger oxidative stress. They are usually referred to as antioxidants; some of them can be versatile compounds that exert such a role in various ways. This review summarizes, from a chemical point of view, the antioxidant effects of relevant molecules found in coffee. Their ways of action and trends in activity are analyzed, considering the data gathered so far from both theory and experiments. The influence of the media and pH in aqueous solution, and structure-activity relationships are discussed. The protective role of the explored compounds is examined. A particular section is devoted to derivatives of some coffee components, and another one to their bioactivity. Hopefully, the information provided here will promote further investigations into the amazing chemistry contained in our morning cup.

This work aimed to develop an easy-to-use smartphone-based electrochemical biosensor to quickly assess coffee blend's total polyphenol (Phs) content at industrial and individual level. The device is based on a commercial carbon-based screen-printed electrode (SPE) modified with multi-walled carbon nanotubes (CNTs) and gold nanoparticles (GNPs). At the same time, the biotransducer, Laccase from Trametes versicolor, TvLac, was immobilized on the sensor surface by using glutaraldehyde (GA) as cross-linking agent. The platform was electrochemically characterized to ascertain the influence of the SPE surface modification on its performance. The working electrode (WE) surface morphology characterization was obtained by scanning electron microscopy (SEM) and Fourier-transform infrared (FT-IR) imaging. All the measurements were carried out with a micro-potentiostat Sensit Smart by PalmSens connected to a smartphone. The developed biosensor provided a sensitivity of 0.12 μA/μM, a linear response ranging from 5 to 70 μM, and a lower detection limit (LOD) of 2.99 μM. Afterwards, the biosensor was tested for quantifying the total Phs content in coffee blends, evaluating the influence of both the variety and the roasting degree. The smartphone-based electrochemical biosensor performance has been validated though the Folin-Ciocâlteu standard method.

In the last years, a recent growing line of research has been developed with fruitful results by using fractional and conformable derivatives in the iterative procedures of classical methods for solving nonlinear equations. In that sense, the use of conformable derivatives has shown better behavior than fractional ones, not only in the theory, but also in the practice. In this work, we adapt the approximation of conformable derivatives in order to design the first conformable derivative-free iterative schemes to solve nonlinear equations: a Steffensen’s type method and a Secant type method; the latter with memory. Convergence analysis is made, preserving the order of classical cases, and the numerical performance is studied in order to confirm the results in the theory. It is shown that these methods can present some numerical advantages versus their classical partners, with wide sets of converging initial estimations.

Post-translational modifications (PTMs) represent a cornerstone in the complexity of the proteome, significantly contributing to diversifying protein structure and function. PTMs can significantly influence protein function, stability, localization, and interactions with other molecules. Therefore, it is important when choosing a protein expression system to ensure the precise incorporation of PTMs during protein synthesis, which is paramount for producing biologically active proteins. Cell-free protein synthesis (CFPS) system has emerged as a powerful protein synthesis platform and research toolkit in synthetic biology. The open nature of the system allows the reaction environment to be tailored to any protein of interest to promote specific PTMs, thus allowing for the production of a protein with the desired modifications. This review presents various PTMs achieved in the CFPS systems, providing insights into the current challenges, successes, and future prospects.

With the intensive development of data transmitting and processing devices of the terahertz (THz) frequency range, an important part of which are integrated plasmonic components and communication lines, it becomes necessary to measure correctly the optical constants of their conductive surfaces. In the paper we describe a reliable method for determining the effective permittivity εm of a metal surface from the measured characteristics (refractive and absorption indices) of THz surface plasmon polaritons (SPPs). The novelty of the method is the conduction of measurements on a metal surface with a dielectric layer of subwavelength thickness, suppressing the radiative losses of SPPs, which are not taken into account by the SPP dispersion equation. The method was tested on a number of flat "gold sputtering - zinc sulfide layer - air" structures with the use of the THz radiation (λ0 = 141 μm) of the Novosibirsk free electron laser (NovoFEL). The SPP characteristics were determined from interferograms measured with a plasmon Michelson interferometer. It was found that the method allowed a significant increase in the accuracy of εm in comparison with measurements on the same metal surface without a dielectric layer.