There has been a growing call for reform of the U.S. biomedical community in recent years. As a community, we face a growing list of issues including excessive waste, reproducibility, bias, inadequate training, and the absence of sustainable long-term planning that detract from the overall goal of advancing human health. In response to this debate, biomedical stakeholders have taken positive steps forward to remedy these issues. However, we must continually improve upon these steps to promote the long-term stability of the biomedical enterprise. Given the widespread interest of the scientific community in addressing these issues, there exists a unique opportunity to come together and create a new era of biomedical discovery. The completion of this exciting task requires reflection on our view and management of the system, and what the best route to sustainable change may be. Importantly, a coordinated approach that considers the collective make-up of the biomedical system and how processes and people influence collective output and create value for patients is needed. Here, these three areas and the concepts of systems theory, total quality management, and organizational development and their contribution to the management and effectiveness of biomedical discovery are discussed. Importantly recommendations are made concerning overall management strategy, process efficiency and quality research, administrative tasks, organizational cultural challenges, individual and team development, and funding strategy.

In this paper, we present a novel Two-Echelon Ground Vehicle and Its Mounted Unmanned Aerial Vehicle Cooperated Routing Problem (2E-GUCRP). The 2E-GUCRP arises in the field of Unmanned Aerial Vehicle (UAV) Routing Problem such as those encountered in the context of city logistics. In a typical cooperated system, the UAV is launched from the Ground Vehicle (GV) and automatically flies to the designated target. Meanwhile, acting as a mobile base station, the GV can charge or change the UAV’s battery on the designated landing points to enable the UAV to continue its mission. The objective is to design efficient GV and UAV routes to minimize the total mission time while meeting the operational constraints. A Mixed Integer Programming (MIP) model, which could be solved by commercial software, is constructed to describe this problem. In order to quickly solve the medium-scale problems, two existing heuristics to solve 2E-VRP are improved. The computational experiments are set up to compare our model with the 2E-VRP. The results indicate that the 2E-GUCRP obtains a better efficiency. Further discussion of the practical instance points out that the increase in efficiency is related to the speed relationship between the GV and the UAV.

The co-circulation of duck hepatitis A virus subtypes 1 (DHAV-1) and 3 (DHAV-3) in ducklings has resulted in significant economic losses. Because ducklings infected with DHAV-1 or DHAV-3 show similar clinical signs and gross lesions, it is important to discriminate these subtypes as early as possible for better clinical management. On the basis of multiple alignments of the 5′-noncoding region sequences of strains DHAV-1 and DHAV-3, universal and type-specific primers were designed and synthesized. Using the primers in a one-tube reverse transcription-PCR (RT-PCR) assay, reference strains of DHAV-1 and DHAV-3 (isolated over a span of 60 years and covering many different countries) were successfully amplified, indicating that the primer sequences were completely conserved. The amplicon sequences results and the sizes of amplicons from reference DHAV-1 and DHAV-3 isolates correlated completely with their genotypes. Moreover, with this one-tube RT-PCR system, the amplicon sizes of liver samples of reference DHAV-1- or DHAV-3-infected birds matched perfectly with their respective genotypes, as determined by virus isolation and neutralization tests. No other RNA viruses of duck origin were detected with the synthesized primers. The sensitivity of viral RNA detection was 10 pg. With this system, 20% genotype 1, 45% genotype 3, and 9% co-infection of the two genotypes were detected in 55 clinical samples. This novel approach could be used for the rapid genotyping DHAV-1 and/or DHAV-3 infection in routine clinical surveillance or epidemiologic screening.

The purpose of this study was to identify different adolescent profiles identified by their use tobacco/alcohol and violent behavior repertoires as well as to analyze the extent to which they show impulsivity traits. Participants were selected by cluster random sampling. There was a total of 822 high school students in the sample aged 13 to 18 years with a mean of 14.84 (SD=.87). A cluster analysis with the following variables was done to form the groups: Use of tobacco, Use of alcohol, Physical aggression, Verbal aggression, Anger and Hostility. Three groups of adolescents resulted from these five variables. The multivariate comparison demonstrated the existence of significant between-group differences, and individual analysis for each of the dependent variables (impulsivity dimensions) showed that the relationship was statistically significant in all cases. In conclusion, analysis of factors possibly associated with adolescent’s risk behavior makes possible and orients intervention in different stages of development for sustainable consumption in adolescents.

The current energy policy recommends the idea of energy efficiency over fossil energy as a primary matter for the coming years. The kingdom of Morocco requires restructuring of its power equipment by increasing the percentage of renewable energy supplies, optimizing their systems and power storage. Therefore, increasing energy efficiency is an as important obligation as reducing the overall energy consumption. The purpose of this research is to present the energy transition in Morocco towards renewable energies and to assess the diversity of available marine natural resources. Recent research in conversion of ocean thermal energy, wave energy, tidal energy, offshore wind energy, and osmotic energy into power supply has started to encourage different technologies. This research has led to commercial deployment in some cases such as our 550 km long Mediterranean coast and 3000 km long Atlantic. This does not only result in fossil energies independency but also provides advantages like less cost and no pollution.

The total, soluble and insoluble oxalate contents of fresh and wok-fried fat hen (Chenopodium album) leaves were extracted and measured using HPLC chromatography. The total oxalate content of the raw leaves was 1112.4 mg/100 g dry matter (DM), and the levels were significantly reduced by boiling (682.8 mg/100 g DM) or cooking the leaves in a wok (883.6 mg/100 g DM). The percentages of soluble oxalate contents in the total oxalates of the raw and boiled leaves were similar (mean 75%), while the proportion of soluble oxalate content in the wok-fried leaves were reduced to 53.4% of the total, giving a significant increase in the insoluble oxalate content of the wok-fried leaves. The percentage of insoluble calcium in the total calcium was significantly reduced (P < 0.05) when the leaves were boiled but the insoluble oxalate content significantly increased (67.2%) in the wok-fried leaves when compared to the content of the original raw leaves. Processing the cooked leaves into pesto or extracting the juice gave final products that contained significantly reduced total and soluble oxalate contents. The addition of calcium chloride to the juice made a very small reduction in the soluble oxalate content in the juice.

Leaves of Rubus idaeus are a raw material, ingredients of herbal blend and a source of antioxidants. There are no data concerning histochemistry of trichomes and little is known about the leaves structure of this species. The aim of this study was to determine the histochemistry of active compounds and the structure of glandular trichomes, micromorphology, anatomy and ultrastructure of leaves as well as content of elements. To determine the histochemistry of glandular trichomes different chemical compounds were used. The leaves structure was analysed using light, scanning, and transmission electron microscopes. The content of elements was determined with atomic absorption spectrometry and the microanalysis of the epidermis ultrastructure was carried out with transmission electron microscope equipped with a digital X-ray analyser. In glandular trichomes: polyphenols, terpenes, lipids, proteins, and carbohydrates were identified. The main elements in the ultrastructure of the epidermis were: Na, S, Ca, Mg, B, Mo, and Se. In dry matter of leaves K, Mg, Ca, P, and Fe were dominant. Infusions from leaves are safe for health in terms of the Cd and Pb concentrations. Leaves can be a valuable raw material. Non-glandular trichomes prevent clumping of mixed raw materials in herbal mixtures.

Background: The prognostic value of erythrocyte levels of the n-6 fatty acids (FAs) for total mortality and cardiovascular disease (CVD) outcomes remains an open question. Methods: We examined CV outcomes and death in 2500 individuals in the Framingham Heart Study Offspring cohort without prevalent CVD (mean age 66 years, 57% women) as a function of baseline levels of different length n-6 FAs (18 carbon, 20 carbon and 22 carbon) in the erythrocyte membranes. Clinical outcomes were monitored for up to 9.5 years (median follow up, 7.26 years). Cox proportional hazards models were adjusted for a variety of demographic characteristics, clinical status and RBC n-6 and long chain n-3 FA content. Results: There were 245 CV events, 119 CHD events, 105 ischemic strokes, 58 CVD deaths, and 350 deaths from all causes. Few associations between either mortality or CVD outcomes were observed for the n-6 FAs, with those that were observed becoming non-significant after adjusting for n-3 FA levels. Conclusions: Higher circulating levels of the marine n-3 FA levels are associated with reduced risk for incident CVD and ischemic stroke and for death from CHD and all-causes, however in the same sample, little evidence exists for association with n-6 FAs. Further work is needed to identify a full profile of FAs associated with cardiovascular risk and mortality.

In a two-year field trial, the effect of nitrogen (N) and sulfur (S) fertilization was investigated on grain yield, grain quality parameters, formation of acrylamide (AA), and the precursor free asparagine (Asn) in organically and conventionally produced winter wheat cultivars. In both production systems, different types, amounts, and temporal distributions of N were tested. While the effect of S fertilizer types and amounts on free Asn was only tested in the conventional farming system. Within both cropping systems, grain yield and baking quality were significantly influenced by N treatment while the effect on free Asn was only minor. Especially within the organic farming system, increasing N fertilization levels did not increase free Asn significantly. A slight trend of increasing free Asn levels with an intensified N supply was observed, especially in the presence of crude protein contents of 14% or higher. But only N amounts of 180 kg N ha⁻¹ or higher increased the probability of high free Asn contents considerably, while N supply below that amount led to free Asn values similar to the unfertilized controls. The results indicated that good baking quality can be achieved without significantly increasing free Asn levels. In addition, cultivars affected the levels of free Asn significantly. Compared to cv. “Bussard” and “Naturastar”, cv. “Capo” exhibited the lowest AA formation potential at an N supply of 180 kg N ha⁻¹ while simultaneously reaching a crude protein content > 15% (conventional) and > 12% (organic). Thus, it seems that cultivars differ in their ability to store and incorporate free Asn into proteins. Over all trials, a correlation of free Asn and AA was shown by R² = 0.77, while a relation of free Asn and protein was only R² = 0.36. Thus, lowering free Asn by adjusting N treatments should not necessarily affect baking quality. S nutrition within conventional farming did not change free Asn amount or crude protein significantly, probably due to the fact that soil was not sulfate-deficient. In summary, it was evident that free Asn amounts in wheat varied widely both within cultivars and between cropping systems. In order to clearly unravel genotypic differences and their interaction with environmental factors and especially N fertilization, further research is needed.

Novel multifunctional fluorescent chemosensors composed of electrospun (ES) nanofibers with high sensitivity toward pH, mercury ions (Hg²⁺), and temperature were prepared from poly(N-Isopropylacrylamide-co-N-methylolacrylamide-co-rhodamine derivative) (poly(NIPAAm-co-NMA-co-RhBN2AM)) by employing electrospinning process. NIPAAm and NMA moieties provide hydrophilic and thermo-responsive properties (absorption of Hg²⁺ in aqueous solutions), and chemical cross-linking sites (stabilization of the fibrous structure in aqueous solutions), respectively. The fluorescent probe, RhBN2AM is highly sensitive toward pH and Hg²⁺. Synthesis of poly(NIPAAm-co-NMA-co-RhBN2AM) with different compositions were carried on via free-radical polymerization. ES nanofibers prepared from sensory copolymers with a 71.1:28.4:0.5 NIPAAm: NMA: RhBN2AM ratio (P3 ES nanofibers) exhibited significant color change from nonfluorescent to red fluorescence while sensing pH or Hg²⁺, and high reversibility of on/off switchable fluorescence emission when Hg²⁺ and ethylenediaminetetraacetic acid (EDTA) were sequentially added. The P3 ES nanofibrous membranes had a higher surface-to-volume ratio to enhance their performance than did the corresponding thin films. In addition, the fluorescence emission of P3 ES nanofibrous membranes exhibited second enhancement above the lower critical solution temperature. Thus, the ES nanofibrous membranes prepared from P3 with on/off switchable capacity and thermo-responsive characteristics can be used as multifunctional sensory devise for specific heavy transition metal (HTM) in aqueous solutions.

Imperatorin is a chemical compound belong to Linear furan coumarins. Imperatorin is attracting considerable attention because of its anti-tumor, antibacterial, anti-inflammatory, anticoagulant and inhibition of myocardial hypetrophy and other pharmacological efficacy. However, imperatorin has limited water solubility and preferable lipid solubility, we decided to design and synthesize imperatorin lipid microsphere, to optimize preparation conditions. The aim was to develop and formulate imperatorin lipid microsphere through nano emulsion technology and apply the response surface-central composite design to optimize the imperatorin lipid microsphere formulation. Influence of content of amount of egg lecithin(A), amount of poloxamer188(B), soybean oil for injection accounted for the total percentage of oil phase(C) were investigated. Integrated effect of dependent variables including particle size(Y₁), polydispersity index(Y₂), Zeta potentials(Y₃), drug loading(Y₄), encapsulation efficiency(Y₅). Data of overall desirabiities were fitted to a second-order polynomial equation, through which three dimensional response surface graphs were described. Optimum experimental conditions were calculated by Design-Expert 8.06. Results indicated that the optimum preparation conditions were as follows: egg lecithin amount 1.39 g, poloxamer188 amount 0.21 g, soybean oil for injection amount 10.57%. Preparation of imperatorin lipid microsphere according to the optimum experimental conditions resulted in an overall desirability of 0.7286, while the particele size (168±0.54) nm, polydispersity index (PDI) (0.138±0.02), Zeta potentials (−43.5±0.5) mV, drug loading (0.833±0.27) mg·mL⁻¹, encapsulation efficiency (90±1.27)%. The difference between observed and predicted values of the overall desirability of the optimum formulation was in range from 2.4% to 4.3%. Subsequently, using the Scanning electron microscopy to observe the micromorphology of imperatorin lipid microsphere, the result shows that round globular of relatively uniform and sizes within 200nm.The proliferation study of imperatorin lipid microsphere on MDA-MB-231 was investigated by MTT method. Furthermore, pharmacokinetics in Sprague Dawley rats were evaluated using orbital bleeding. A sensitive and reliable liquid chromatography with High Performance Liquid Chromatography (HPLC) method was established and validated for the quantification of imperatorin in rat plasma samples. The data were calculated by DAS (Drug and statistics) pharmacokinetic software version3.2.6 (China). Results demonstrated that imperatorin lipid microsphere can significantly enhance the bioavailability of imperatorin and can significantly inhibit MDA-MB-231 cell proliferating. In conclusion, our results suggersted that the response surface-central composite design is suitable for the optimized lipid microspere formulation. Imperatorin Lipid microsphere can improve the bioavailability of imperatorin and inhibit the proliferation of MDA-MB-231 than that of imperatorin.

Bioenergy produced from perennial feedstocks such as woody biomass could serve as an opportunity to strengthen local and regional economies and also jointly produce various environmental services. In order to assess the potential for biomass- based bioenergy, it’s essential to characterize the interest that potential biomass suppliers have in such an endeavor. In the U.S. Great Plains region, this largely means assessing relevant perceptions of farmers and ranchers. We conducted a series of farmer and rancher oriented focus groups in North Dakota, South Dakota, Nebraska and Kansas to qualitatively explore opinions about the role that trees can play in agriculture and interest in woody biomass systems within existing Northern Great Plains (NGP) farms and ranches. Our findings suggest that farmer and ranchers generally value the role that trees, or tree-based practices like windbreaks can play in agriculture particularly on marginal farmland in terms of conservation or crop protection. Yet relative to the potential of trees as a biomass crop there is a distinct lack of knowledge and skepticism. Farmers and ranchers also noted variable degrees of risk concern and uncertainty regarding investing in tree-based systems, as well as a number of perceived external market related constraints to integrating trees within their managed systems. Most of the participants recognized that if biomass production or an increase in tree planting and management in general were to expand in the NGP region, government programs would likely be required to provide much needed technical guidance and financial incentives. As the NGP regional bioeconomy continues to emerge and expand, private and public investment relative to niche bioenergy feedstocks such as woody biomass should address the type of information needs that farmers and ranchers have relative to integrating biomass production into existing farm and ranch systems.

We investigate the ammonium removal abilities of natural and synthetic zeolites, which have distinct Si/Al ratios and various surface areas, to study how adsorption and ion-exchange processes in zeolites perform under different ammonium concentrations and different temperatures. Five zeolites including natural mordenite, chabazite, erionite, clinoptilolite and synthetic merlinoite were immersed in 20 mg/kg, 50 mg/kg and 100 mg/kg ammonium solutions. The results demonstrate that zeolites under high ammonium concentrations (100 mg/kg) possess higher physical adsorption capacity (0.398–0.468 meq/g), whereas those under lower ammonium concentrations (20 mg/kg) possess greater ion-exchange property (64–99%). The ion-exchange ability of zeolites are extremely dependent on the cation content of the zeolites, and the cation content is affected by the Si/Al ratio. The surface area of zeolites also has a partial influence on its physical adsorption ability. When the surface area is less than 100 m²/g, the adsorption ability of zeolite increases obviously with surface area; however, adsorption ability is saturated as the surface area becomes larger than this critical value of 100 m²/g. When we carried out the zeolites in 50 mg/kg ammonium concentration at different temperatures (5~50 ℃), we found that zeolites exhibit the highest ammonium removal ability at 30°C and the potassium release was enhanced at 30~40 ℃.

The Canal of Aragon and Catalonia (CAC) is 134 km long and irrigates 105,000 ha (131 irrigation user communities) and it is own by the River Ebro’s Water Agency. The aqueducts are located between km 67 and 71 of the canal and were designed by the Civil Engineer Félix de los Ríos Martín in 1907. The cross-section of both aqueducts, Coll de Foix and Capedevila, was extended within the framework of the project by Fernando Hué Herrero in 1962 in order to reach design flows of 26.1 m3/s and 25.7 m3/s, respectively. The structural performance of the aqueducts has been satisfactory, nevertheless the hydraulic capacity has reduced over the years. As a result, the irrigation user communities have expressed the need to extend the cross-section of the aqueducts to meet the irrigation demands. Given the age of the structure and the different design considerations at the time, it is paramount to verify the structural reliability of the aqueducts in the new load configuration. Therefore, the objective of the paper is to present the structural safety analysis conducted and describe the new extended cross-section for both aqueducts (maintaining the original structural typology).

Genetic testing has expanded out of the research laboratory into medical practice and the direct-to-consumer market, and rapid analysis of the resulting genotype data can now have significant impact. We present a method for summarizing personal genotypes as ‘genotype fingerprints’ that meet these needs. Genotype fingerprints can be derived from any single nucleotide polymorphism (SNP)-based assay, and remain comparable as chip designs evolve to higher marker densities. We demonstrate that they support distinguishing types of relationships among closely related individuals and closely related individuals from individuals from the same background population, as well as high-throughput identification of identical genotypes, individuals in known background populations, and de novo separation of subpopulations within a large cohort through extremely rapid comparisons. While fingerprints do not preserve anonymity, they provide a useful degree of privacy by summarizing a genotype in a way that prevents reconstruction of individual marker states. Genotype fingerprints are therefore well-suited as a format for public aggregation of genetic information to support ancestry and relatedness determination without revealing personal health risk status.

Versatile hybrid organic polymers are prepared using two active intermediates such as cynuric chloride and chitosan derivatives. The prepared chalcones are characterized by using FT-IR, UV, and proton NMR, thermal analysis and Minimum inhibitory Concentration. Thermal stability of the synthesized hybrid polymer is found using TGA and the hybrid chitosan derivative chalcone is thermally stable up to 270 °C. The antimicrobial activity of the prepared chitosan containing chalcone moiety are find out using Minimum Inhibitory Concentration (MIC) method. The synthesized versatile chalcone shows excellent antimicrobial activity against gram-negative bacteria such as Pseudomonas aeruginosa; and Gram-positive bacteria Chalcone containing halogen moiety shows high activity (MIC 7.8 µg/mL) than the hydroxyl containing chalcone. Cytotoxicity activity of the synthesized composites shows high activity.

This paper highlights the impact of financial inclusion on individuals’ borrowing and saving decisions in the United States and the United Arab Emirates. It does so, using data from the 2014 Global Financial Inclusion database, and an empirical strategy consisting of first testing the significance of the joint bivariate model over its binary conterparts using the Lagrange multiplier test, followed by a contrast between the fully-parametric and semi-parametric specifications of the saving and borrowing equations. Based on model performance measures, the semi-parametric bivariate probit specification is identified as a better framework for describing the two processes of saving and borrowing, with a correlation coefficient of 12.3%. Although no significant difference exists between UAE and US residents in borrowing behavior, we find that US residents are 31.4% more likely to save than their UAE counterparts. In addition, and in line with the Permanent Income Hypothesis, the results reveal the absence of an income based saving or borrowing gradient in the two countries. Conversely, we found the prevalence of a gender based saving (12.4%) and borrowing (13.8%) inequality in favor of the male gender. Furthermore, access to a bank account and a debit card, companies policy of direct wage and salary transfer, and government transfer programs with direct deposit options are all financial inclusion strategies that are found to significantly raise the likelihood of saving and borrowing. As such, companies with payroll practices based on cash or physical paycheck issuing, especially in the US, should revise such policy to create more financial inclusion, and thereby more saving potential which in turn would contribute to further borrowing, investment and growth of the national economy.

While over half of all spinal cord injuries (SCIs) occur in the cervical region, the majority of preclinical studies have focused on models of thoracic injury. However, these two levels are anatomically distinct—with the cervical region possessing a greater vascular supply, grey-white matter ratio and sympathetic outflow relative to the thoracic region. As such, there exists a significant knowledge gap in the secondary pathology at these levels following SCI. In this study, we characterized the systemic plasma markers of inflammation over time (1, 3, 7, 14, 56 days post-SCI) after moderate-severe, clip-compression cervical and thoracic SCI in the rat. Using high-throughput ELISA panels, we observed a clear level-specific difference in plasma levels of VEGF, leptin, IP10, IL18, GCSF, and fractalkine. Overall, cervical SCI had reduced expressions of both pro- and anti-inflammatory proteins relative to thoracic SCI, likely due to sympathetic dysregulation associated with higher level SCIs. However, contrary to the literature, we did not observe level-dependent splenic atrophy with our incomplete SCI model. This is the first study to compare the systemic plasma-level changes following cervical and thoracic SCI using level-matched and time-matched controls. The results of this study provide the first evidence in support of level-targeted intervention and also challenge the phenomenon of high SCI-induced splenic atrophy in incomplete SCI models.

With the availability of wearable health monitoring sensor modules like 3-Lead Electrocardiogram (ECG), Pulse Oximeter (SpO2), Galvanic Skin Response (GSR), Hall effect sensor (for measuring Respiratory Rate), Blood Pressure and Temperature measuring and sensing elements, it has now become possible to device a composite health status monitoring kit that can measure vital signs and other physiological parameters pertaining to human health in real time. Traditionally, the physiological parameters along with vital signs related examination was possible only in a hospitalized or ambulatory environment, however due to advances in sensing and embedded system technology and miniaturization of data acquisition and processing elements health monitoring has become possible even when individuals remain engaged in their day to day activities at the convenience of space and location. The patients or individuals subject to monitoring may suffer from a traumatic experience due to their medical condition and may need emergent incidence response and the critical care team may have to prepare for the treatment only after the patient arrives, which often is too late, as in case of cardiac arrests or severe injuries. The research focused on real-time health status monitoring and trauma scoring using standard physiological parameters along with standard telemetry protocols to make the critical care team aware of an emergent situation and prepare for a medical emergency. Vital signs and physiological parameters (heart rate, temperature, respiratory rate, and blood pressure, SpO2) were measured in real time from human subjects non-invasively. In order to enable monitoring of the patients engaged in day to day activities, errors due to the motion were removed using stationary wavelet transform correction (correlation coefficient of 0.9 after correction) and signals from various sensors were denoised, filtered and were encoded in a format suitable for further data analysis. A composite sensor kit capable of monitoring vital signs and physiological parameters can be very useful in incident response when an individual undergoes a traumatic experience related to stroke, cardiac arrest, fits or even injury, as along with monitoring information the kit can calculate scores related to trauma like the Injury Severity Score (ISS), National Early Warning Signs (NEWS), Revised Trauma Score (RTS). Trauma Injury Severity Score (TRISS), Probability of Survival (Ps) score. An open access database of vital signs and physiological parameters from Physionet, MIMIC 2 Numerics (mimicdb/numerics) database was used to calculate NEWS and RTS and to generate correlation and regression models using the vital signs/physiological parameters for a clinical class of patients with respiratory failure and admitted to Intensive Care Unit (ICU). NEWS and RTS scores showed no significant correlation (r = 0.25, p<0.001) amongst themselves, however together NEWS and RTS showed significant correlation with Ps (blunt) (r = 0.70, p<0.001). RTS and Ps (blunt) scores showed some correlation (r = 0.63, p<0.001) and NEWS score showed significant correlation (r = 0.79, p<0.001) with Ps (blunt) scores. Furthermore, since individuals have to be monitored regardless of location, these kits have to have a built-in capability to locate the individual so that the incident response team can locate the individual based on Global Positioning System coordinates (GPS). A Quantum GIS (Geographical Information System) application using real-time GPS coordinates (OpenStreetMap coordinates) was used to calculate the shortest path using QGIS Network Analysis tool to demonstrate the calculation of shortest path and direction to locate the nearest service provider in shortest time. Along with locating the nearest healthcare service provider, it would help if the critical care team could be made aware of the physiological parameters and trauma scores using standard protocols accepted across the globe. The physiological parameters from the sensors along with the calculated trauma scores were encoded according to a standard Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) coding system and International Code of Diseases (ICD) codes and the trauma information was logged to Electronic Health Records (EHR) using Fast Health Interoperability Resources (FHIR) servers. FHIR servers provided interoperable web services to log the event information in real time. It could be concluded that analytical models trained on existing datasets can help in analyzing a traumatic experience or an injury and the information can be logged using a standard telemetry protocol as a telemedicine initiative. These scores enable the healthcare service providers to estimate the extent of trauma and prepare for medical emergency procedures and find applications in general and military healthcare.

The application of graph theory in chemical and molecular structure research far exceeds people's expectations, and it has recently grown exponentially. In the molecular graph, atoms are represented by vertices and bonded by edges. In this report, we study the silicon-carbon Si₂C₃-I[p,q] and Si₂C₃-II[p,q]. We compute several Zagreb polynomials and Redefined Zagreb indices of these silicon-carbons.

Site environments and instrumental characteristics of carbon dioxide (CO₂) measurements operated by local governments in the Kanto Plain, the center of which is Tokyo were summarized for this study. The observation sites were classified into environments of three types: urban, suburban, and woodland. Based on a few decades of accumulated hourly data, the diurnal and seasonal variations of CO₂ concentrations were analyzed as a composite of anomalies from annual means recorded for each site. In urban areas, the highest concentrations appear before midnight in winter. The second peak corresponds to the morning rush hour and strengthening of the inversion layer. Suburban areas can be characterized as having the highest concentration before dawn and the lowest concentration during the daytime in summer in association with the activation of respiration and photosynthesis of vegetation. In these areas, concentration peaks also appear during the morning rush hour. Woodland areas show background features, with the highest concentration in early spring: higher than the global background by about 5 ppmv.

This paper explores as a case study the development of e-cigarette use and smoking within small friendship group (n=8) in Glasgow, Scotland. Interviewed twice at six months apart these 16/17 year olds reported substantial change in their use of and attitudes towards e-cigarettes and tobacco. At time 1 vaping generated much excitement and interest, with 6/8 having their own vape device. At time 2 only two young people still vaped, with the others no longer professing any interest in continued vaping. The two regular smokers, who had been smoking before they first vaped, now only vaped privately and to reduce their tobacco intake. This small case study illustrates plasticity in the use of electronic cigarettes; just as young people can initiate using these devices so too can they more away from their use- with such changes in actual use occurring within a relatively short period of time. These findings demonstrate more than anything else the volatility in young peoples’ substance use behaviour. If we are to better understand these behaviours we require both quantitative and qualitative research studies that are capable of both monitoring changes in individual and group behaviour over time but which are also able to elucidate the nuance of individual behaviour differentiating between long term, frequent, consistent use and more episodic, experimental and infrequent use by young people.

Although ladybirds of European Russia and the Caucasus have been the subject of numerous ecological and faunistic investigations, there is an evident lack of appropriate identification key for them. All previous keys have been published in Russian. The most modern key was published more than 50 years ago and included only about 60 % of species. Guides for identification of Coccinellidae of other countries are not appropriate for European Russia, since do not include many species occurring in the regions. New, original key to subfamilies, genera, and species of ladybirds (Coccinellidae) of the European Russia and Russian Caucasus is presented. All native species recorded in the region and all alien species introduced to this region are included. Some species from the adjacent regions are added. In total, 110 species are keyed and illustrated with line drawings. Photographs of rare and endemic species are provided. Information on the distribution of species within the region under consideration is provided. Synonymy of Chilocorus kuwanae with Ch. renipustulatus is presented and discussed.

Environmental deterioration factors are constantly increasing, causing unwanted aesthetic changes to stone artworks due to exposure to various physical and chemical deterioration factors. Inorganic nanoparticle-filled polymer composites have extended their multiple functionalities to various applications, including cultural heritage conservation. Therefore, this study has examined the effects of clay, SiO2, Ca(OH)2 and CaCO3 nanomaterials in the enhancement of the physicomechanical properties of limestone monuments, the aim of the present work being to evaluate comparatively the effectiveness of nanoparticles as consolidation and protection material for limestone artworks. The nanoparticles were added to an acrylic-based copolymer (polyethylmethacrylate (EMA)/methylacrylate (MA) (70/30), in order to improve its physiochemical and mechanical properties, and produced a significant improvement in the ability of the polymers to consolidate and protect the stone. The synthesis process of nanoparticles/polymer nanocomposite has been prepared by an in situ emulsion polymerization system. The nanocomposites contained poly (EMA/MA) with a solid content of 3% [poly (EMA/MA)] in the absence and presence of 5% nanoparticles (0.15 g nanoparticles). Samples were subjected to artificial aging by relative humidity/temperature and acid/salt crystallization weathering to show the optimum conditions of durability and the effectiveness of the nano-mixture in improving the physical and mechanical properties of the stone material. To ensure that the treatment had no negative effects on the physical characteristics of the limestone, the properties of the treated limestone samples were evaluated comparatively before and after artificial aging by the conduct of microstructural (phase morphology studied by means of scanning electron microscopy) and aesthetic (colour and lightness measured by spectrophotometry) analyses. Also used were measurement of static contact angle of water droplets on the surface of the samples, total immersion water absorption, compressive strength, and abrasion resistance test. Results demonstrated that the addition of nanoparticles to an acrylic-based polymer enhanced its capability to consolidate and protect the limestone samples.

Energy conversion and distribution (heat and electricity) is characterized by long planning horizons, investment periods and depreciation times, and it is thus difficult to plan and tell the technology that optimally fits for decades. Uncertainties include future energy prices, applicable subsidies, regulation, and even the evolution of market designs. To achieve higher adaptability to arbitrary transition paths, a technical concept based on integrated energy systems is envisioned and described. The problem of intermediate steps of evolution is tackled by introducing a novel paradigm in urban infrastructure design.It builds on standardization, modularization and economies of scale for underlying conversion units. Building on conceptual arguments for such a platform, it is then argued how actors like (among others) municipalities and district heating system operators can use this as a practical starting point for a manageable and smooth transition towards more environmental friendly supply technologies, and to commit to their own pace of transition (bearable investment/risk). environmental friendly supply technologies. Merits are not only supported by technical arguments but also by strategical and societal prospects like technology neutrality and availability of real options.

Hydrothermal pyrite is an important source of thallium (Tl) but this rare element can be also detected in the secondary iron goethite-lepidocrocite and jarosite ores, associated to hydrothermal kerogen, manganese oxides, accessorial potassium minerals and tiny Tl-bearing clusters shielded in quartz masses. We studied Tl-bearing samples collected from Fe-Mn ores hosted in dolostone rocks sited along ca. 15 km of fossil thermal springs following a geological fault in the Lodares surroundings. Samples were analyzed by environmental scanning electron microscopy and energy dispersive spectroscopy (ESEM-EDS), electron probe micro-analysis (EPMA), inductively coupled plasma-mass spectroscopy (ICP-MS), X-ray diffraction analysis (XRD), Tl LIII-edge X-ray absorption near-edge structure (XANES) spectroscopy, Micro-Raman and Fourier transform infrared spectroscopy (FTIR). We found epithermal pyrite, sphalerite, galena and baryte and secondary gypsum, jarosite, scorodite, anglesite, goethite, epsomite and elemental sulfur produced by both hydroxylation and bacterial processes. The highest Tl contents were found in hydrothermal pyrite (200 mg kg-1), kerogen (13 mg kg-1), manganese ores (27 mg kg-1) and iron sulfate-hydroxides (142 mg kg-1). The aquatic kerogen was formed in a marine environment and later heavily carbonized during the hydrothermal processes. The Lodares outcrops exhibit interesting details on the geochemical cycle of Tl in a genetic frame of epithermal formation of pyrite and kerogen.

Bipolar neutrosophic set is an important extension of bipolar fuzzy set. This set is a hybridization of bipolar fuzzy set and neutrosophic set. Every element of a bipolar neutrosophic set consists of three independent positive membership functions and three independent negative membership functions. In this paper, we develop cross entropy measures of bipolar neutrosophic sets and prove its properties. We also define cross entropy measures of interval bipolar neutrosophic sets and prove its properties. Thereafter, we develop two novel multi-attribute decision making methods based on the proposed cross entropy measures. In the decision making framework, we calculate the weighted cross entropy measures between each alternative and the ideal alternative to rank the alternatives and choose the best one. We solve two illustrative examples of multi-attribute decision making problems and compare the obtained result with the results of other existing methods to show the applicability and effectiveness of the developed method. In the end, the main conclusion and future scope of research are summarized.

This paper considers two types of Protestant ethnic groups of some areas of Urals and Western Siberia. The first type consist of representatives of members of different ethnic groups consisting of well-educated professionals, incorporated into industrial society and associated with the intellectualism of Protestantism. The second type is represented by the indigenous peoples of the Polar Urals and Western Siberia, who use the Protestant religious organizations as tool for restoring life-sustaining elements of the native peoples’ traditional economy. I employed the inductive approach and the comparison method; during the fieldwork I used ethnographic participant observations, sociological structured interviews and closed-ended questionnaires. The empirical data have been collected in the Southern, Middle and Polar Urals and Western Siberia.

Assessment of the trends of land cover and vegetation dynamics (VD) using remote sensing (RS) and indicators such as anthropogenic activities and the socio-demographic information is essential in order to make proper planning for sustainable management. This paper attempts to evaluate land cover change (LCC) and VD in Kebbi State, Nigeria using historical Landsat data from 1986-2016 by means of remote sensing. The Driver-Pressure-State-Impact-Response (DPSIR) framework was later employed using both primary and secondary data for a better understanding of the drivers, the state of the environmental condition, the causes as well as the impact of the change. The images were classified into five thematic land cover classes as Dense Vegetation, shrubs/built area, farmland, bare/grassland and water body by means of Maximum likelihood supervised classification technique in accordance with Anderson classification scheme level 1, with acceptable accuracy. Pre-classification and post-classification change detection (CD) methodologies were executed using Normalized difference vegetation index (NDVI) and Image differencing respectively. The study illustrates a steady decline in dense vegetation and shrubs/build areas while farmland and bare/grassland increases, however, water bodies remain unchanged. The DPSIR pin-point that the major drivers of change in the study area have been the pressing need for farming land as the population grows and socioeconomic demands including fuelwood consumption and endemic poverty. Expansion of Farming land, fuelwood consumption and the need for construction materials are identified as the main key elements exerting pressure for the change. The state of the condition indicates a steady decline in dense vegetation and shrubs areas while farmland and bare/grassland are increasing significantly. The impacts include land degradation, the decline in the provision ecosystem goods and services, biodiversity loss through loss of habitats. The study, however, noted that many international and national policies in response to land degradation are channelled toward land restoration and remediating of the environment, through afforestation programs and improving the livelihood of the rural people through providing alternative income sources since they depend heavily on land for sustenance. However, the state governments, communities and individual commonly organized annual tree planting campaign with the main purpose of environmental protection.

The review is devoted to the physical, chemical and technological aspects of the breath-figures self-assembly process. Main stages of the process and the impact of the polymer architecture and physical parameters of the breath-figures self-assembly on the eventual pattern are covered. The review is focused on the hierarchy of spatial and temporal scales inherent for the breath-figures self-assembly. Multi-scale patterns arising from the process are addressed. The characteristic spatial lateral scales of patterns vary from nanometers to dozens of micrometers. The temporal scales of the process span from micro-seconds to seconds. The qualitative analysis performed in the paper demonstrates that the process is mainly governed by the interfacial phenomena, whereas the impact of inertia and gravity is negligible. Characterization and applications of polymer films manufactured with breath-figures self-assembly are discussed.

A series of novel N-n-butyl-1,8-naphthalimide derivatives were synthesized via a three-step reaction involving nucleophilic substitution and acylation. All of the compounds were characterized by IR, ¹H NMR, ¹³C NMR, MS, and elemental analysis, and the crystal structure of N-n-butyl-4-[N’,N’-bis(2`,4`-dichlorobenzoyl)ethylamino]-1,8-naphthalimide was determined. The π-π stacking interactions and hydrogen bonds between the two molecular core planes (naphthalimide ring) and the van der Waals forces between the flexible n-butyl groups resulted in a 3D long-chain structure. The UV-vis and fluorescence properties of the title compounds were investigated. The results indicated that the monosubstituted 1,8-naphthalimide derivatives bearing an electron-donating group on the benzene ring or a structure with a larger conjugative effect exhibited enhanced fluorescence properties.

Recently emerging data-driven citizen sciences need to harness increasing amount of massive data with varying quality. This paper develops essential theoretical frameworks and example models and examine its computational complexity for interactive data-driven citizen science within the context of guided self-organization. We first define a conceptual model that incorporates quality of observation in terms of accuracy and reproducibility, ranging between subjectivity, inter-subjectivity, and objectivity. Next, we examine the database's algebraic and topological structure in relation to informational complexity measures, and evaluate its computational complexities with respect to exhaustive optimization. Conjectures of criticality are obtained on self-organizing processes of observation and dynamical model development. Example analysis is demonstrated with the use of biodiversity assessment database, the process that inevitably involves human subjectivity for the management in open complex systems.

To study the influence of Latin dance and Tai Chi on knee joint proprioception and balance. Method: All experiments were performed in the Beijing Normal University School of Physical Education and Sport Biomechanics Laboratory. An isokinetic test system (Biodex system 4, BS4) and a balance testing system (Biodex Balance System, BBS)from the United States Biodex medical system were used to test related indexes. Results: In the LOS test, the overall score of Latin group is much better than sedentary group. In the ASL test, Latin group have a better balance ability in anterior and posterior direction and overall score than sedentary group(p＜0.05); TAI CHI group have a better balance ability than sedentary group in anterior and posterior direction(p＜0.05)and right and left direction (p＜0.01). When the knee joint was at 15, 30, and 45degree positions, the Tai Chi exercise group was much better than sedentary group (P < 0.05), and the 45 degree position in the Tai Chi group was much better than that in the Latin dance group (P < 0.01).When the knee joint was at the 30 degree position, the quadriceps force sense was significantly better in the Tai Chi group than in the Latin dance and sedentary groups. In a test of the four angles, the hamstring force sense in the Tai Chi exercise group was obviously better than that in the sedentary group (P < 0.05); at the 15 degree position, the Tai Chi group was significantly better than the Latin group (P < 0.05); and at 30 degree position, the hamstring force sense of the Latin group was obviously better than that of the sedentary group (P < 0.05).

In this study, we evaluated the physicochemical and microbial qualities of source and stored household waters in some communities in Southwestern Nigeria using standard methods. Compared parameters include physicochemical constituents; Temperature (T), pH, Total Dissolved Solids (TDS), Total Hardness (TH), Biological Oxygen Demand (BOD), Magnesium ion (Mg²⁺) and Calcium ion (Ca²⁺) and microbiological parameters included Total Coliform Counts (TC), Faecal Coliform Counts (FC), Fungal Counts (Fung C), Heterotrophic Plate Counts (HPC). Comparing Stored and Source samples, the mean values of some physicochemical parameters of most of the stored water samples significantly (P<0.05) exceeded that of Sources and ranged in the following order: T (15.3±0.3^oC - 28.3±0.5^oC), pH (6.4±0.1 - 7.6±0.1), TDS (192.1±11.1 ppm - 473.7±27.9 ppm), TH (10.6±1.7 mg/L - 248.6±18.6 mg/L), BOD (0.5±0.0 mg/L - 3.2±0.3 mg/L), Mg²⁺ (6.5±2.4 mg/L - 29.1±3.2 mg/L) and Ca²⁺ (6.5±2.4 mg/L - 51.6±4.4 mg/L). The mean microbial counts obtained from microbial comparison of different points (Stored and Source) of collection showed that most of the stored water had counts significantly exceeding (P<0.05) those of the source water samples (cfu/100 mL) which ranged as follows: TC (3.1±1.5 - 156.8±42.9), FC (0.0±0.0 - 64.3±14.2) and HPC (47.8±12.1 - 266.1±12.2) across all sampled communities. Also, the predominant isolates recovered from the samples were identified as Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Enterobacter aerogenes, Aspergillus spp, Mucor spp, Rhizopus spp and Candida spp. The presence of these pathogenic and potentially pathogenic organisms in the waters and the high counts of the indicator organisms suggest the waters to be a threat to public health.

Crystal structures of simple metals and binary alloy phases based on the face-centered cubic (fcc) structure are analyzed within the model of Fermi sphere – Brillouin zone interactions to understand the stability of original cubic structure and derivative structures with distortions, superlattices and vacancies. Examination of the Brillouin-Jones configuration in relation to the nearly-free electron Fermi sphere for several representative phases reveals significance of the electron energy contribution to the phase stability. Representation of complex structures in the reciprocal space clarifies their relationship to the basic cubic cell.

Propionibacterium acnes and Staphylococcus epidermidis are the major skin bacteria that cause the formation of acne. The present study was conducted to investigate antibacterial activity of ethanolic extract of cinnamon bark, honey and their combination against acne bacteria. The antibacterial activity of extract of cinnamon bark and honey were investigated against P. acnes and S. epidermidis using disc diffusion method. Minimum Inhibitory Concentration (MIC) and minimal bactericidal concentration (MBC) were performed using Clinical and Laboratory Standard Institute (CLSI) methods. The interaction combination between extract of cinnamon bark and honey was determined by using a checkerboards method. The results showed that he MIC of extract of cinnamon bark and honey against P. acne were 256 µg/mL and 50% v/v, respectively, while against S. epidermidis were 1024 µg/mL and 50% v/v, respectively. The MBC of extract of cinnamon against P. acnes and S. epidermidis were more than 2048 µg/mL, whereas the MBC for honey against P. acnes and S. epidermidis were 100%. The combination of cinnamon bark extract and honey against against P. acnes and S. epidermidis, showed additive activity with the FICI value 0.625. Therefore, the combination of extract of cinnamon bark and honey has potential activity against acne causing bacteria.

This study explores the relationship between job satisfaction, employee loyalty and two types of flexible employment arrangements; teleworking and flexi-time. The analysis relies on data derived by the Workplace Employee Relations Survey (WERS) in 2004 and 2011. A propensity score matching and least squares regressions are applied. Furthermore, Bayesian Networks (BN) and Directed Acyclic Graphs (DAGs) are employed in order to confirm the causality between employment types explored and the outcomes of interest. Finally, an instrumental variables (IV) approach based on the BN framework is proposed and applied in this study. The results support that there is a positive causal effect from these employment arrangements on job satisfaction and employee loyalty.

The interplay between wildfires and drought stress has significantly limited forest recovery in the Mediterranean ecosystem of central Chile. Since 2010, the region has faced a prolonged 'Mega Drought,' which intensified into a 'Hyper Drought' in 2019, with record-low precipitation and high temperatures, further constraining forest recovery amidst increasing wildfire frequency. This study evaluates short-term vegetation recovery across drought gradients in three sclerophyllous evergreen forests, analyzing Landsat time series (1987–2022) for 42 wildfires. Using the LandTrendr algorithm, we assessed post-fire forest recovery based on NDVI changes between pre-fire values and subsequent years. The results revealed significant differences in recovery across drought gradients and fire severity interactions. After five years, the xeric forest dominated by Quillaja saponaria and Lithrea caustica showed 89% recovery during the Mega Drought and 34% during the Hyper Drought. In contrast, the mesic forest dominated by Cryptocarya alba and Peumus boldus exhibited 28% recovery during the Mega Drought and 43% during the Hyper Drought. Degraded thorny shrublands showed the lowest recovery, averaging 23% under Hyper Drought and medium fire severity. These findings underscore the critical role of prolonged, severe drought in shaping forest recovery dynamics and highlight the need to understand these patterns to improve future forest resilience under increasingly arid conditions.

Aβ1-42 (amyloid beta) oligomers, the major neurotoxic culprits in Alzheimer's disease, initiate early pathophysiological events, including neuronal hyperactivity, that underlie aberrant network activity and cognitive impairment. Although several synaptotoxic effects have been extensively studied, neuronal hyperexcitability which may also contribute to cognitive deficits is not fully understood. Here, we found several adverse effects of in vivo injection of Aβ1-42 oligomers on contextual memory and intrinsic properties of CA1 pyramidal neurons. Male rats underwent behavioral and electrophysiological studies 1 week after microinjections into the dorsal CA1 region, followed by histological analysis. After 1 week, Aβ1-42 oligomers impaired contextual learning without affecting basic physiological functions and triggered training-induced neuronal excitability. Furthermore, riluzole, a persistent sodium current (INaP) blocker, dose-dependently reduced Aβ1-42 oligomer-induced hyperexcitability. Congo red staining, which detects insoluble amyloid deposits, further identified labeling of CA1 pyramidal neurons while immunohistochemistry with lecanemab, which detects soluble Aβ oligomers, revealed immunoreactivity of both pyramidal and non-pyramidal cells in the target area. Therefore, our study suggests that a single injection of Aβ1-42 oligomers resulted in contextual memory deficits along with concomitant neuronal hyperexcitability and amyloid deposition in the CA1 region after 1 week.

Background/Objectives: Traditional neurosurgical training involves a steep learning curve. The introduction of advanced simulation technologies, such as virtual reality (VR), provides an alternative method for skill acquisition, allowing for repeated practice and objective assessment. This study focuses on evaluating the learning curve associated with lumbar pedicle Kirschner wire insertion using a virtual fluoroscopic simulator among neurosurgical residents. Methods: Eighteen neurosurgery residents and two interns participated in this study. Participants’ initial skill levels were assessed through a questionnaire. Performance metrics, including insertion accuracy, time, and the number of virtual X-ray scans, were recorded across multiple attempts until a “practical learning plateau” was reached. Statistical analyses were conducted to model learning curves, assess the correlation between pre-training experience and performance. Results: The average number of attempts required to stabilize performance was 5.61. Learning rates varied, with some residents showing rapid improvement while others progressed more slowly. Higher accuracy in wire placement correlated with reduced usage on X-rays over time. However, experienced residents did not necessarily learn faster, indicating potential challenges in adapting to new simulation-based methods. Post-training feedback highlighted the simulator’s utility in increasing confidence and skill levels, although some limitations in anatomical accuracy were noted. Conclusions: This study demonstrates the potential of virtual simulation to enhance neurosurgical training by providing a controlled environment for repeated practice and objective feedback. Simulation-based training can effectively complement traditional methods, though individualized approaches may be necessary to accommodate varying learning rates among residents. Further refinement of simulation tools and their integration into standard training curricula are recommended.

The use of natural health products (NHP) is constantly increasing worldwide. Among the most NHP consumed are the resins of Commiphora myrrha (C. myrrha) tree. Consumption of C. myrrha may result in herb-drug interactions that can lead to serious health consequences. This study aims to determine the herb-drug interactions based on the induction of drug-metabolizing enzyme cytochrome P-450 (CYP) 2C9 by a non-toxic boiled aqueous extract of C. myrrha and to unveil the potential involvement of xenobiotic-sensing nuclear receptors such as Pregnane X Receptor (PXR), a well-known CYP 2C9 transcription factor. Tested at low concentrations (0.01-10 g/mL) devoid of anti-proliferative effects, boiled C. myrrha resin aqueous extract upregulated CYP 2C9 gene and protein expressions in a dose-dependent manner, reaching a mean expression level exceeding 3.0-fold change in Hep G2 cells, compared with the basal level expressed in untreated cells. Furthermore, chemical analysis using mass spectrometry and computational molecular docking using in silico studies revealed that few C. myrrha resin-derived metabolites are strongly bound to PXR. In particular, the identified metabolite named diayangambin exhibited a predicted molecular docking score close to that of a native PXR ligand. The use of the nuclear receptor binding assays confirmed the binding between C. myrrha metabolite(s) and PXR, while no binding to the other xenobiotic-sensing nuclear receptor, the constitutive androstane receptor (CAR), was observed, suggesting that C. myrrha metabolite(s) are potential PXR agonists. In conclusion, although in vivo studies are needed, this study cautions patients, healthcare providers, and governmental regulators against the consumption of C. myrrha and diayangambin-rich preparations with a high potential for herb-drug interactions through drug-metabolizing CYP 2C9 enzyme induction, which could affect drug efficacy.

The selection of the best allogeneic donor for each specific patient is crucial for the success of allogeneic hematopoietic stem cell transplantation (HSCT). Besides the well-known patient’s characteristics, donor-related variables such as patient-donor histocompatibility and donor age are of utmost importance for the outcome after HSCT. However, there is still debate on the definition of the best stem cell donor when multiple suitable donors exist. By using own data from two transplant centers, we here developed a calculator able to provide the 2-year patients’ overall survival (OS) associated to each of the potential donor options during the selection process. Data on n=737 HSCTs performed from January 2010 to July 2022 have been retrospectively obtained. Donor types were HLA-identical siblings, unrelated or related haploidentical. Cox regression and parametric model indicates patients’ age, disease, comorbidity index and donor type as significant variables (p<0.05) able to predict 2-year OS with robustness (concordance index: 0.677). Estimates are provided with the three donor options for each single, specific patient. Of note, estimates express real data of the transplant centers and reflect their actual experience. In conclusion, we here present the prototype of a new tool for the calculation of patients’ outcome according to the stem cell donor type, guiding transplant physicians during the process of donor selection before HSCT. The novelty of this approach relies on the use of real data from the investigating centers, reflecting the local clinical experience. Improvements are planned by filling additional information and pooling data from more centers.

In mammals, fatty acid transport protein 1 (FATP1) is involved in cellular long-chain fatty acid (LCFA) uptake and activation, especially in processes of transportation, oxidation and triglyceride synthesis. However, the role of Fatp1 in invertebrates, especially decapod crustaceans, is still poorly understood. In this study, the cDNA of a fatp1 gene of a decapod crustacean, mud crab Scylla paramamosain, was cloned and functionally characterized. The fatp1 gene encoded a polypeptide of 643 amino acids that possessed all the typical features of the Fatp family, and shared high homology with the other Fatp orthologs of crustaceans. The relative expression levels of fatp1 were higher in metabolically active tissues such as hepatopancreas, stomach and gill than the other parts of crabs. Knockdown of the fatp1 gene in vivo reduced triglyceride and total lipid levels in the hepatopancreas, and increased the tissue expression levels of genes related to fatty acid transportation, allocation and hydrolysis including long-chain acyl-CoA synthetase 3/4 (acsl3/4) and carnitine palmitoyl transferase 1 (cpt1), and decreased expression levels of genes related to fatty acid synthesis such as acetyl-CoA carboxylase (acc) and fatty acid synthase (fas). Increased dietary n-3 LC-PUFA levels resulted in the up-regulation of fatp1 gene expression in the hepatopancreas, and the increase in LC-PUFA content, especially EPA and DHA, in both polar and nonpolar lipids in hepatopancreas and muscles of crabs. The data collectively suggested that the fatp1 gene, identified in S. paramamosain, might play important roles in regulating fatty acid absorption, utilization and allocation in crustaceans.

Necroptosis is a regulated form of cell death implicated in several pathological conditions, in-cluding viral infections. In this study, we investigated the expression and correlation of necroptosis markers, MLKL, RIP1 and RIP3, in human liver tissue from fatal cases of yellow fever (YF) using immunohistochemistry (IHC). Liver samples were obtained from 21 YF-positive individuals and five flavivirus-negative controls with preserved liver parenchymal architecture. The cases un-derwent histopathological analysis, followed by tissue immunostaining with the immuno-histochemical method of streptavidin-biotin peroxidase. Using the in situ method, we evaluated the centrilobular (Z3), midzonal (Z2), periportal zone and portal tract (PT) zones of human liver parenchyma with markers for necroptosis, RIPK1, RIPK3 and MLKL. Quantitative analysis re-vealed significantly higher expression of MLKL, RIP1 and RIP3 in the liver parenchyma of YF cases compared to controls in different zones (Z3, Z2, Z1) and portal tracts (PT) of the liver, especially in zone 2. Immunostaining confirmed the localization of MLKL, RIP1 and RIP3 in hepatocytes and inflammatory infiltrates, highlighting their involvement in the pathogenesis of YF. Pearson's correlation analysis demonstrated significant correlations between necroptosis markers which indicate their coordinated regulation during YF-induced liver injury.

Background: Despite procedural advancements in the management of univentricular heart patients palliated with a Fontan-type circulation, their exercise capacity and quality of life remain limited. Postoperative exercise training programs offer potential benefits, yet practical implementation and adherence to guidelines are often inadequate. This systematic review and meta-analysis aimed to evaluate the safety, efficacy, and optimal exercise modalities for Fontan patients. Method: A systematic search was conducted on August 24, 2023, using PubMed, Scopus, Web of Science, and Cochrane Library. Studies were screened via Rayyan QCRI based on pre-set exclusion criteria, and their quality was assessed using the Cochrane RoB Tool 2 and the STROBE checklist. A meta-analysis employed a continuous random-effects model to assess the efficacy of cardiac rehabilitation interventions. Results: The study included twenty-six studies (7 RCTs, 19 cohorts) representing 22 individual cohorts. The key findings were that aerobic exercise, lower-extremity resistance training, and inspiratory muscle training significantly improved VO2, enhancing exercise capacity in Fontan patients. Conclusion: While the results are promising, it's crucial to remember that training programs varied widely. Exercise training shows promise for postoperative management, potentially improving exercise capacity, cardiac biomarkers, lung function, and lower limb strength. However, further research is not just a suggestion, but a necessity. It's necessary to refine protocols, assess long-term impacts, and investigate underlying mechanisms, especially for Fontan patients with severe clinical conditions. This emphasizes the importance and urgency of further research in this area.

Autism spectrum disorder (ASD) involves social communication difficulties and repetitive behaviors, with a growing prevalence worldwide. Symptoms include cognitive impairments, gastrointestinal (GI) issues, feeding difficulties, and psychological problems. A significant concern in ASD is food selectivity, leading to nutrient deficiencies. Common GI issues in ASD, such as constipation and irritable bowel syndrome, stem from abnormal gut flora and immune system dysregulation. Sensory sensitivities and behavioral challenges exacerbate these problems, correlating with neurological symptom severity. Children with ASD also exhibit higher oxidative stress due to low antioxidant levels like glutathione. Therapeutic diets, including ketogenic, high-antioxidant, gluten-free, and casein-free, show potential in managing ASD symptoms like behavior, communication, GI issues, and oxidative stress, though the evidence is limited. Various studies have focused on different populations, but there is increasing concern about the impact on children. This review examines the effect of food selectivity, GI problems, and antioxidant deficiencies in ASD and revises the effectiveness of various therapeutic diets, highlighting the need for further research to confirm their long-term benefits.

Developing short-term forecasting model for global atmospheric temperature and wind in the near space is crucial for understanding atmospheric dynamics and supporting human activities in this region. While numerical models have been extensively developed, deep learning techniques have recently shown promise in improving atmospheric forecasting accuracy. In this study, convolutional long short-term memory (ConvLSTM) and convolutional gated recurrent unit (ConvGRU) neural networks were applied to build for short-term global-scale forecasting model of atmospheric temperature and wind in the `near space based on the MERRA-2 reanalysis dataset from 2010-2022. The model results showed that the ConvGRU model outperforms the ConvLSTM model in the short-term forecast results. The ConvGRU model achieved a root mean square error in the first three hours of approximately 1.8 K for temperature predictions, and errors of 4.2 m/s and 3.8 m/s for eastward and northward wind predictions, respectively.

Papillomaviruses (PVs) are oncogenic and infect the skin and mucosa of various host species. Considering the recent advances in research on PVs using rolling circle amplification (RCA) followed by high-throughput sequencing (HTS), in this study, we aimed to investigate the bovine papillomavirus (BPV) types associated with proliferative lesions in the upper alimentary tract of an affected bull and characterize the viral strains through complete genome sequencing using this strategy. We analyzed the PV strains associated with two hyperplastic esophageal lesions through PCR using degenerate primer pairs and RCA, followed by HTS. HTS of the libraries generated using RCA products provided the whole genome sequence of BPV4 present in squamous papilloma, whereas, the complete genome sequence of BPV2 and subgenomic fragments of BPV4 were identified in carcinoma in situ (CIS). We, for the first time, have sequenced BPV2 identified from the CIS of the bovine upper alimentary canal. Additionally, RCA followed by HTS allowed characterization of the mixed infection by BPV2 and BPV4 in this lesion. These data reveal that BPV4 is not the only BPV type present in CIS of the esophageal mucous membrane; moreover, a mixed infection caused by BPV2 and BPV4 at the tested anatomical site was demonstrated.

Many studies have demonstrated hydrogen's therapeutic and preventive effects on various diseases. Its selective antioxidant properties against hydroxyl radicals, which are responsible for the indirect effects of ionizing radiation, may make it worthy of attention as a new radio-protector. We recently developed new hydrogen water that is more stable and has higher antioxidant activity by using ultra-fine bubbles. In this study, female C57BL/6J mice given ad libitum access to ultra-fine bubble hydrogen water (UBHW) were subjected to whole-body irradiation (WBI) with X-rays, and the radio-protective effect of UBHW was evaluated. Sub-lethal WBI resulted in a 30-day survival rate of 100% in UBHW-fed mice, compared with 37% in control mice. In the case of lethal WBI, while the control mice died out in about 3 weeks, the 30-day survival rate improved to 40% by UBHW due to the high scavenging activity of hydroxy radicals. Twenty-six serum proteins involved in inflammatory and immune responses were significantly identified in UBHW-fed mice by proteomics, and UBHW may enhance and regulate these functions, resulting in reduced damage in mice exposed to WBI. We conclude that UBHW has good potential in radio-protection, with evidence that warrants further research efforts in this field.

Much evidence now indicates a direct crosstalk between thyroid hormones (THs) and the immune system. We previously showed that THs behave as anti-inflammatory agents in human leukemic THP-1 monocytes, but a potential neuroprotective effect of THs in microglia have been under-investigated. Microglia, the primary innate immune cells of the brain, play a pivotal role in the regulation of neuroinflammation and nongenomic integrin αvβ3-mediated action of THs appear to be involved. Integrin αvβ3 was highly expressed in activated BV-2 cells, while it was decreased by THs. In addition, THs facilitated wound healing in BV-2 murine microglia cells activated by lipopolysaccharide (LPS), through integrin αvβ3 and reactive oxygen species (ROS), with tetrac (a metabolite of TH) potentiated the inhibition of migration. Nitric oxide (NO) played a role with different mechanisms in the presence of either T3 or T4. Our data showed the capability of TH and analogues to modulate the M1-to-M2 microglial transition and suggest a new spectrum of actions in the central nervous system (CNS).

Background: Low back pain (LBP) is a major cause of disability globally, and the diagnosis of LBP is challenging for clinicians. Objective: This study aimed to assess the accuracy level of arti-ficial intelligence as a Clinical Decision Support System (CDSS) called Therapa compared to MRI in predicting lumbar disc herniated patients. Methods: One hundred low back pain patients aged ≥18 years old were included in the study. The study was conducted in 3 stages, at first, a case se-ries was conducted by matching MRI and Therapha diagnosis for 10 patients. Subsequently, Delphi methodology was employed to establish a clinical consensus. Lastly, to determine the ac-curacy of the newly developed software, a cross-sectional study was undertaken, involving 100 patients. Results: The software showed a significant diagnostic accuracy with the area under the curve in the ROC analysis determined as 0.84 with a sensitivity of 88% and a specificity of 80%. Conclusion: The study’s findings revealed that CDSS using Therapha has a reasonable level of ef-ficacy, and this can be utilized clinically to acquire faster and more accurate screening of patients with lumbar disc herniation.

Green peppers (Capsicum annuum L.) is a fruit vegetable with great culinary versatility, and present important nutritional properties for human health. Water deficit negatively affects nutritional quality of green peppers fruits. This study aimed to investigate the influence of zinc oxide nanoparticles (ZnONPs), associated with plant growth-promoting bacteria (PGPB), on the post-harvest quality nutritional of green peppers subjected to water deficit. In an open-field ex-periment, two irrigation levels (50 and 100% of crop evapotranspiration - Etc), four treatments composed by combination of ZnONPs, zinc sulfate (ZnSO4) and PGPB (T1 = ZnSO4, T2 = foliar ZnONPs, T3 = foliar ZnONPs + PGPB, T4 = ZnSO4 via soil + PGPB via soil) and a control treatment (Check) were tested. Water deficit or water deficit mitigation treatments did not interfere with the physical-chemical parameters (except vitamin C content) and physical color parameters (except L*) of green pepper. The water deficit reduced the levels of Ca, Mg, P, K, Mn, Fe, B, and Zn in the fruits. The foliar application of ZnONPs in association with PGPB provided better nutritional quality of green pepper in terms of vitamin C and mineral nutrients. Under water deficit, ZnONPs or ZnSO4 via foliar, associated or not with PGPB, increased the levels of Ca, P, Mg, and Fe in the fruits. Applying Zn via foliar as ZnONPs or ZnSO4 mitigated the negative effects of water deficit on the quality of pepper fruits that was enhanced by the Bacillus subtilis and B. amyloliquefaciens inoculation.

Overweight/obesity and cardiovascular diseases are associated with high rates of mobility and mortality. We investigated inflammatory lesions and ionic transporters in the left ventricle of male rats chronically fed a high-fat diet (HL). They developed moderate overweight with early expansion of visceral adiposity. The inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-), Na+-transporting ATPases, sarco-endoplasmic reticulum Ca2+-ATPase (SERCA2a), and the abundance of Angiotensin II receptors were studied together with lipid and glycemic profiles, and the left ventricle echocardiographic parameters fractional shortening (FS) and ejection fraction (EF). HL rats doubled IL-6 and TNF-, which returned to normal levels when signaling coupled to Angiotensin II type 2 receptors (AT2R) was supraregulated by Ang-(3–4) administration. The decreased glucose tolerance was accompanied by significantly reduced plasma triglycerides due to intense hepatic steatosis (Crisóstomo et al. Metabolism Open. 2022, 14, 100176). AT2R (and AT1R) abundance did not change. (Na++K+)ATPase and ouabain-resistant Na+-ATPase were downregulated and upregulated, respectively, normalized with Ang-(3–4). SERCA2a lost its most critical regulatory property, inhibition by excess substrate. The ultrasound showed no changes in FS and EF. We conclude that very moderate overweight can cause silent initial molecular tissue damage in heart, which can evolve to cause systolic dysfunction.

The IMbrave150 trial established atezolizumab with bevacizumab (A+B) as standard care for hepatocellular carcinoma (HCC), recommending an esophagogastroduodenoscopy (EGD) within 6 months of treatment initiation to prevent bleeding from esophagogastric varices. The necessity of mandatory EGD for all patients remains unclear. We retrospectively analyzed 112 HCC patients treated with A+B at five Canadian cancer centers from July 1, 2020, to August 31, 2022. A+B was the first-line therapy for 90% of patients, with median overall survival at 20.3 months and progression-free survival at 9.6 months. There was no survival difference between patients with bleeding and those without. Before A+B, 71%(79) of patients underwent an EGD within 6 months, revealing varices in 41%(32) and requiring intervention in 19%(15). The overall bleeding rate was 15%(17), with GI-specific bleeding occurring in 83%(5) of the EGD group and 17%(1) of the non-EGD group (p=0.24). Non-GI bleeding was observed in 10%(11) of patients. Outcomes for HCC patients treated with A+B in Canada were comparable to IMbrave150. Our study showed twice the rate of varices detection and treatment compared to IMbrave150, reflecting real-world treatment of high-risk populations. There was no increased GI bleeding in patients without pre-treatment EGD, supporting a selective EGD approach.

Background: The Risk of Paradoxical Embolism (RoPE) score was developed to identify stroke-related patent foramen ovale (PFO) in patients with cryptogenic stroke. Methods: We conducted a retrospective analysis of the 2016 to 2020 National Inpatient Sample to determine the performance of modified RoPE score for PFO presence in patients with acute ischemic stroke (AIS). Results: A total of 3,338,805 hospital admissions for AIS were analysed and 3.0% had PFO. Patients with PFO were younger compared to those without PFO (median 63 years vs. 71 years, p&lt;0.001) and fewer were female (46.1% vs. 49.7%, p&lt;0.001). The patients with PFO had greater mean modified RoPE score (4.0 vs. 3.3, p&lt;0.001). The area under the curve for the RoPE score in predicting PFO was 0.625 (95%CI 0.620-0.629). The best diagnostic power of the RoPE score was achieved with a cut point of ≥4 where the sensitivity was 55% and the specificity was 64.2%. A cut point of ≥5 increased specificity (83.1%) at the expense of sensitivity (35.8%). The strongest predictor of PFO was deep vein thrombosis (OR 3.97, 95%CI 3.76-4.20). Conclusions: The modified RoPE score had modest predictive value in identifying patients with PFO among patients admitted with AIS.

Rutin, a flavonoid compound found in various plants, has gained attention for its potential applications in the cosmetic industry due to its antioxidant, anti-inflammatory, and potential photoprotective properties. Our review explored the use of rutin (rutoside, 3-O-rutinoside-quercetin) in cosmetics/dermocosmetics, focusing on its physicochemical properties and stability, cutaneous permeability, and efficacy in sunscreen systems, involving in vitro tests and the current state of clinical trials. Rutin's ability to scavenge free radicals, prevent peroxidation, and reduce vascular fragility makes this flavonoid a promising ingredient for photoprotection. Studies have shown that rutin can enhance the sun protection factor (SPF) of sunscreen formulations, especially when combined with organic UV filters. The encapsulation of rutin in nanostructures has also been investigated to improve its applicability. Overall, rutin shows potential as a safe and effective ingredient in cosmetic/dermocosmetic formulations, offering protection against the harmful effects of UV radiation and oxidative stress on the skin.

Image-guided radiotherapy supported by surface guidance can help track lower lung lesion respiratory motion while reducing a patient’s exposure to ionizing radiation. However, it is not always clear how skin respiratory motion magnitudes and correlations with lung lesion respiratory motion vary between different skin regions of interest (ROI). Four-dimensional Computed Tomography (4DCT) images provide information on both skin and lung respiratory motion and are routinely acquired for the purpose of treatment planning in our institution. Analysis of 4DCT images for 57 patients treated in our institution has been conducted to provide information on respiratory motion magnitudes of nine skin ROIs of the torso, a tracking structure (TS) representing lower lung lobe lesion, as well as respiratory motion correlations between nine ROIs and TS. The effects of gender and adipose tissue volume and distribution on these correlations and magnitudes have been analyzed. Significant differences between ROIs in both respiratory motion magnitudes and correlations to TS have been detected. An overall negative correlation between ROI respiratory magnitudes and the adipose tissue has been detected for ROIs with rib cage support. A weak to moderate negative correlation between adipose tissue volume and ROI-to-TS respiratory correlations has been detected for upper thorax ROIs. Respiratory magnitudes in regions without rib support tended to be larger for men than for women, but no differences in ROI-to-TS correlation between sexes have been detected. Described findings should be considered when choosing skin surrogates for lower lung lesion motion management.

1) Background: carbapenem-resistant Acinetobacter baumannii (CRAB) is an opportunistic Gram-negative pathogen that has a significant role in healthcare-associated infections. Unlike several studies on the antibiotic-resistant epidemiology of A. baumanni, virulence molecular epidemiology was less studied. This study aimed to investigate CRAB virulence genes and their ability to form biofilms, and to correlate their biofilm formation ability with both; biofilm-encoding virulence genes and carbapenemase-encoding resistance genes. 2) Methods: 107 CRAB clinical isolates were collected from two hospitals in Jordan between 2018 and 2019 and were screened for virulence genes using PCR. In addition, biofilm formation ability was assessed using the microtiter plate method. 3) Results: the frequencies of the bap, OmpA, surA, PLD, paaE, basD, and traT virulence genes were 99.10%, 98.20%, 98.20%, 95.50%, 89.10%, 86.40%, and 8.20%, respectively. Overall, 86.4% of the tested isolates were biofilm formers with varying degrees; weak (28.2%), moderate (36.4%) and strong (21.8%). A significant relationship was found between the carbapenemase-encoding gene (OXA-23 gene) and biofilm production. 4) Conclusion: to the best of our knowledge, this is the first study in Jordan that inspected CRAB virulence genes and highlighted the importance of improving infection control measures to avoid CRAB outbreaks.

This work addresses the challenge of EEG visual multiclass classification into 40 classes for Brain-Computer interface applications, by using deep learning architectures. The visual multiclass classification approach offers BCI applications a significant advantage, since it allows the supervision of more than one BCI interaction, considering that each class label supervises a BCI task. However, because of the nonlinearity and nonstationarity of EEG signals, performing multiclassifiers based on EEG features remains a significant challenge for BCI systems. In the present work, mutual information-based discriminant channel selection and Minimum-Norm Estimate algorithms are implemented to select discriminant channels and enhance EEG data. Hence, deep EEGNet and Convolutional-recurrent neural networks are implemented separately to classify EEG data of image visualization into 40 labels. By using the k-fold cross-validation approach, average classification accuracies of 94.8% and 89.8% were obtained by implementing the aforementioned network architectures, respectively. Satisfactory results obtained with this method offer a new implementation opportunity for multi-task BCI applications by utilizing a reduced number of channels (&lt;50%), compared to those presented in the related literature where the whole set of channels is used.

This article aimed to evaluate, using statistical tools, the generation and composition of urban solid waste (MSW) in the city of Belém, Pará, from nine urban collection sectors in the municipality, and the average nominal income of the population. Approximately 900kg of urban solid waste were col-lected from the municipality in the period from 2021 to 2022. Statistical tests were carried out on hypotheses with 5% significance in comparative evaluations, and their respective average nominal incomes. The results indicated that the organic fraction corresponds to 55.57% of the waste generated in the municipality, 14.26% is inert waste (potentially contaminating) and 0.67% is miscellaneous waste. It was observed that the waste generated by families with high purchasing power tends to contain higher percentages of recyclables, while in families with lower purchasing power the highest percentages tend to be organic. Knowledge of the generation of MSW is fundamental for the choice and dimensioning of operations and processes involved in the management chain at the municipal level. The decentralization of services offered based on solid waste management would enable greater success in serving the population.

In clinical practice, patient assessments rely on established scales. Integrating data from these scales into the International Classification of Functioning, Disability, and Health (ICF) framework has been suggested; however, a standardized approach is lacking. Herein, we tested a new approach to develop a conversion table translating clinical scale scores into ICF Qualifiers based on a clinician survey. The survey queried rehabilitation professionals about which functional independence measure (FIM) item scores (1-7) corresponded to the ICF qualifiers (0-4). A total of 458 rehabilitation professionals participated. The survey findings indicated a general consensus on the equivalence of FIM scores with ICF qualifiers. The median value for each item remained consistent across all item groups. Specifically, FIM 1 had a median value of 4; FIM 2 and 3 had median values of 3; FIM 4 and 5 had median values of 2; FIM 6 had a median value of 1; and FIM 7 had a median value of 0. Despite limitations due to the irreconcilable differences between the frameworks of existing scales and the ICF, these results underline the ICF's potential to serve as a central hub for integrating clinical data from various scales.

This study introduces an efficient strategy for synthesizing polyhydroxyurethane-based multicomponent hydrogels with enhanced rheological properties. In a single-step process, 3D materials composed of Polymer 1 (PHU) and Polymer 2 (PVA or gelatin) were produced. Polymer 1, a crosslinked polyhydroxyurethane (PHU) grew within a colloidal suspension of Polymer 2, forming an interconnected network. The synthesis of Polymer 1 utilized a Non-Isocyanate Polyurethane (NIPU) methodology based on the aminolysis of bis(cyclic carbonate) (bisCC) monomers derived from 1-thioglycerol and 1,2-dithioglycerol (monomers MA and ME, respectively). This method, applied for the first time in Semi Interpenetrating Network (SIPN) formation, demonstrated exceptional orthogonality, since the functional groups in Polymer 2 do not interfere with Polymer 1 formation. Optimizing PHU formation involved a twenty-trial methodology, identifying influential variables such as polymer concentration, temperature, solvent (an aprotic and a protic solvent), and the organo-catalyst used [a thiourea derivative (TU) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)]. The highest molecular weights were achieved under near-bulk polymerization conditions using TU-protic and DBU-aprotic as catalyst-solvent combinations. ME-based PHU exhibited higher (M_w ) ̅ than MA-based PHU (34,100 Da and 16,400 Da, respectively). Applying the enhanced methodology to prepare ten multicomponent hydrogels using PVA or gelatin as the polymer scaffold revealed superior rheological properties in PVA-based hydrogels, exhibiting solid-like gel behavior. Incorporating ME enhanced mechanical properties and elasticity (with loss tangent values of 0.09 and 0.14). SEM images unveiled distinct microstructures, including a sponge-like pattern in certain PVA-based hydrogels when MA was chosen, indicating the formation of highly superporous interpenetrated materials. In summary, this innovative approach presents a versatile methodology for obtaining advanced hydrogel-based systems with potential applications in various biomedical fields.

The clinical practice implies a research translation that helps the use of scientific data and thera-peutic evidence for patient benefits. This review critically summarizes the potential impact of cannabinoids in concomitance with other drugs in the following chronic diseases as Epilepsy, Au-tism Spectrum Disorders (ASD), Oncology, Multiple Sclerosis, and Chronic Pain. The potential in-teractions can change the predicted clinical outcomes of therapeutic protocols and need to be evaluated. Some of the effects would be additive, synergistic or antagonistic, but can also enroll changes in absorption, distribution, metabolism, particularly via cytochrome P450 (CYP) isoen-zymes (e.g CYP2C9 and CYP3A4) and excretion. For instance, the combination of canna-bis-derived compounds and the antifungal drug ketoconazole, a CYP3A4 inhibitor, increases plasma concentration of Δ-9-tetrahydrocannabinol (THC) and CBD (CBD). Opposable, rifampic-in, a CYP3A4 inducer, stands out for the approximately 20-40% reduction in plasma THC levels and 50% to 60% for CBD. Other CYP3A4 inhibitors and inducers are likely to have a similar effect on plasma concentrations if co-administered. Indeed, pharmacokinetic interactions have been also reported with antiseizure drugs. Moreover, pharmacodynamic interactions between cannabinoids and drugs with sympathomimetic effects (eg tachycardia, hypertension), central nervous system depressants (eg drowsiness, ataxia), and anticholinergics (eg tachycardia and drowsiness) are also expected. Even though pending further studies, there is currently clinical evidence supporting drug interaction with cannabinoids, demanding doctors evaluate the risk of drug combinations with cannabinoids. The tables herein provided were designed to facilitate the identification of bi-orelevant interactions that may compromise therapeutic efficacy and toxicity.

It is known that knockdown of the mitochondrial 18 kDa translocator protein (TSPO) as well as TSPO ligands modulate various functions, including functions related to cancer. To study the ability of TSPO to regulate gene expression regarding such functions, we applied microarray analysis of gene expression to U118MG glioblastoma cells. Within 15 minutes, the classical TSPO ligand PK 11195 induced changes in expression of immediate early genes and transcription factors. These changes also included gene products that are part of the canonical pathway serving to modulate general gene expression. These changes are in accord with reverse transcriptase (RT) real-time -PCR. At the time points of 15, 30, 45, and 60 minutes, as well as 3 and 24 hours of PK 11195 exposure, the functions associated with the changes in gene expression in these glioblastoma cells covered well known TSPO functions. These functions included cell viability, proliferation, differentiation, adhesion, migration, tumorigenesis, and angiogenesis. This was corroborated microscopically for cell migration, cell accumulation, adhesion, and neuronal differentiation. Changes in gene expression at 24 hours of PK 11195 exposure were related to downregulation of tumorigenesis and upregulation of programmed cell death. In the vehicle treated as well as PK 11195 exposed cell cultures, our triple labeling showed intense TSPO labeling in the mitochondria but no TSPO signal in the cell nuclei. Thus, mitochondrial TSPO appears to be part of the mitochondria-to-nucleus signaling pathway for modulation of nuclear gene expression. The novel TSPO ligand 2-Cl-MGV-1 appeared to be very specific regarding modulation of gene expression of immediate early genes and transcription factors.

A sustainable green one pot procedure for the synthesis of dihydropyrimidinones (DHPMs) derivatives by a three-component reaction of β-ketoester derivatives, aldehyde and urea or thiourea over the alkali-treated H-ZSM-5 zeolite under ball-milling has been developed. The product was isolated by simple washing of the crude reaction residue with ethyl acetate followed by evaporation of solvent. The hierachical zeolite catalyst (MFI27_6) showed high yield (86–96%) of dihydropyrimidinones (DHPMs), in very short time (10-30 min). The catalyst is recycled for subsequent reactions in four runs without appreciable loss of activity and high yields of products provide efficient protocol for Biginelli reactions.

Diseases in articular cartilages have affected millions of people globally. Although the biochemical and cellular composition of articular cartilages is relatively simple, there is the limitation in self-repair ability of cartilage. Therefore, developing the strategies for cartilage repair is very important. Here, we reported a new manufacturing process of water-based polyurethane based photosensitive materials with hyaluronic acid and applied the materials for 3D printed customized cartilage scaffolds. The scaffold has high cytocompatibility and is one that closely mimics the mechanical properties of articular cartilages. It is suitable for culturing human Wharton's jelly mesenchymal stem cells (hWJMSCs) and the cells showed an excellent chondrogenic differentiation capacity. We consider that the 3D printing hybrid scaffolds may have potential in customized tissue engineering and facilitate the development of cartilage tissue engineering.

Since the first description of bisphosphonate-related osteonecrosis of the jaw (BRONJ) numerous research groups have focused on possible pathological mechanisms including the suppression of the bone turnover of the jaw, antiangiogenic effects and soft tissue toxicity. In our review we focused on summarizing the role of the soft tissues in the development and progression of BRONJ. The biological behavior of fibroblasts can be significantly influenced by bisphosphonates (BP) such as a concentration dependent reduction of cell viability. High concentrations of BP can induce apoptosis and necrosis of the cells. Comparable effects could be detected for keratinocytes. Compared to non-nitrogen containing bisphosphonates nitrogen-containing BP have worse effects on cell biology by blocking the mevalonate pathway. Next to this the cell architecture and the expression levels of several genes and proteins are significantly disturbed by BP. These inhibitory effects of BP are in accordance with BP related reduced angiogenesis and neovascularization and could underline the hypothesis that inhibition of fibroblasts and keratinocytes results in delayed wound healing and can induce and trigger BRONJ.

Amyloid self-assembled from amyloid peptides βΑ40 or βΑ42 is notorious for its neurotoxic effects in plaque and neurofibrillary tangle formations leading to neuron dysfunction and diseases of cognitive decline (e.g. Alzheimer’s, Parkinson’s and Huntington's disease). This contrasts with so-called functional amyloids which are non-toxic ordered template structures amenable to applications in tissue engineering. Amyloid fibrils of variable morphology including long and hollow fibres and flattened tube and spiral ribbon-like structures have been used in engineering applications in nano-biology. Protein assemblies based on amyloid core structures display diverse biological functionalities could be applied in futuristic self-assembling biomaterials in nano-electronics. These possibilities have revolutionized the development of next generation computers and biosensors, ultracapacitors, memristors, actuators, molecular switches and could also be used to develop artificial synapses. Amyloid fibril assemblies have also been used in photoelectric and photon capture light harvesting technologies and been applied in innovative nano-photoelectronics and photovoltaics. Hybrid Aβ(16–22)-α-synuclein amyloid fibrils also exhibit light-harvesting and electron-transfer properties. Engineered amyloid assemblies are thus facilitating innovative futuristic advances in nano-technology. Furthermore, with a better understanding of amyloid fibril assembly processes it may be possible to develop therapeutic methods that prevent the toxic build up of this polymer in brain tissues that leads to diseases of cognitive decline. With the ever-expanding prevalence of these diseases in the ageing general global population, there certainly is a clear and present need to find a remedy for these debilitating conditions.

This work continues the review and illustrative application to energy systems of the “Fourth-Order Best-Estimate Results with Reduced Uncertainties Predictive Modeling” (4th-BERRU-PM) methodology. The 4th-BERRU-PM methodology uses the Maximum Entropy (MaxEnt) principle to incorporate fourth-order experimental and computational information, in-cluding fourth (and higher) order sensitivities of computed model responses with respect to model parameters. The 4th-BERRU-PM methodology yields the fourth-order MaxEnt posterior distribution of experimentally measured and computed model responses and parameters, in the combined phase-space of model responses and parameters. The 4th-BERRU-PM methodology encompasses fourth-order sensitivity analysis (SA) and uncertainty quantification (UQ), which were reviewed in the accompanying work (Part 1), as well as fourth-order data assimilation (DA) and model calibration (MC) capabilities, which will be reviewed and illustrated in this work (Part 2). The applicability of the 4th-BERRU-PM methodology to energy systems is illustrated by using the Polyethylene-Reflected Plutonium (acronym: PERP) OECD/NEA reactor physics benchmark, which is modeled using the linear neutron transport Boltzmann equation, involving 21976 im-precisely known parameters. This benchmark is representative of “large-scale computations” such as those involved in the modeling of energy systems. The result (“response”) of interest for the PERP benchmark is the leakage of neutrons through the outer surface of this spherical benchmark, which can be computed numerically and measured experimentally. The impact of the high-order sensitivities of the response with respect to the PERP model parameters is quantified for “high-precision” parameters (2% standard deviations) and “medium-precision” parameters (5% standard deviations). Analyzing the best-estimate results with reduced uncertainties for the 1st- through 4th-order moments (mean values, covariance, skewness, and kurtosis) produced by the 4th-BERRU-PM methodology for the PERP benchmark indicates that, even for systems mod-eled by linear equations (e.g., the PERP benchmark), retaining only first-order sensitivities is insufficient for reliable predictive modeling (including SA, UQ, DA, MC). At least second-order sensitivities should be retained in order to obtain reliable predictions.

The Simulation analogy presented in this work enhances the accessibility of abstract quantum theories, specifically the stochastic hydrodyanimc model (SQHM), by relating them to our daily experiences. The SQHM incorporates the influence of fluctuating gravitational background, resembling dark energy, into quantum equations. This model successfully addresses key aspects of Objective-Collapse Theories, including resolving the 'tails' problem through the definition of quantum potential length in addition to the De Broglie length, beyond which coherent Schrödinger quantum behavior and wavefunction tails cannot be maintained. The SQHM emphasizes that an external environment is unnecessary, asserting that the quantum stochastic behavior leading to wave-function collapse can be an inherent property of a system in a spacetime with fluctuating metrics. Embedded in relativistic quantum mechanics, the theory establishes a coherent link between the uncertainty principle and the constancy of light speed, aligning seamlessly with finite information transmission speed. Within a fluctuating quantum system, the SQHM derives the indeterminacy relation between energy and time, offering insights into measurement processes impossible within a finite time interval in a truly quantum global system. Experimental validation is found in confirming the Lindemann constant for solid lattice melting points and the transition from fluid to superfluid states. The SQHM's self-consistency lies in its ability to describe wavefunction collapse and the measure process. Additionally, the theory resolves the Pre-existing Reality problem by showing that large-scale systems naturally decay into decoherent states stable in time. Continuing, the paper demonstrates that the physical dynamics of SQHM can be analogized to a computer simulation employing optimization procedures for realization. This perspective elucidates the concept of time in contemporary reality and enriches our comprehension of free will. The overall framework introduces an irreversible process impacting the manifestation of macroscopic reality at the present time, asserting that the multiverse exists solely in future states, with the past comprising the formed universe after the current moment. Decoherence at the present time functions as a reduction of the multiverse to a single universe. The macroscopic reality, characterized by fractal consistency where microscopic domains with quantum properties coexist, provides insights into how our consciousness apprehends dynamic reality, the spontaneous emergence of gravity in discrete spacetime evolution, and the attainment of the classical General Relativity limit in Quantum Loop Gravity and Causal Dynamical Triangulation. The Simulation Analogy highlights a strategy focused on minimizing information processing, facilitating the universal simulation in solving its predetermined problem. From within, reality becomes the manifestation of specific physical laws emerging from the inherent structure of the simulation devised to address its particular issue. In this context, the reality simulation appears to employ an entropic optimization strategy, minimizing information loss while efficiently compressing data in line with the simulation's intended purpose.

Intrauterine growth restriction (IUGR) pigs are characterized by long-term growth failure, metabolic disorders, and intestinal microbiota imbalance. The characteristics of the negative effects of IUGR at different swine growth stages are still unclear. Therefore, this study explored whether intrauterine growth restriction (IUGR) model damaged the intestinal barrier function and altered the colonization and metabolic profiles of the colonic microbiota in growing-finishing pigs by the multi-omics method. Seventy-two piglets (36 IUGR and 36 NBW) were selected for this trial to analyze physiological and plasma biochemical parameters, oxidative damage, and inflammatory response in the colon. Moreover, the colonic microbial communities were examined using 16s rRNA sequencing and metabolomics to reveal the intestinal characteristics of pigs at different growth stages (25, 50, and 100 kg). IUGR altered the plasma concentrations of glucose, total protein triglyceride, and cholesterol. Colonic tight junction proteins were markedly inhibited by IUGR. IUGR decreased plasma T-AOC, SOD, and GSH levels, and colonic SOD-1, SOD-2, and GPX4 expressions by restraining the Nrf2/Keap1 signaling pathway. Moreover, IUGR increased the colonic IL-1β and TNF-α levels while reducing IL-10, possibly activating the TLR4-NF-κB/ERK pathways. Notably, IUGR pigs had lower colonic Streptococcus abundance and Firmicutes-to-Bacteroidetes ratio at the 25 kg BW stage while having higher Firmicutes abundance at the 100 kg BW stage; moreover, IUGR pigs had lower SCFAs concentrations. Metabolomics analysis showed that IUGR increased colonic lipids and lipid-like molecules, organic acids and derivatives, and organoheterocyclic concentrations and enriched three differential metabolic pathways, including linoleic acid, sphingolipid, and purine metabolisms throughout the trial. Collectively, IUGR altered the nutrient metabolism, redox status, and colonic microbial community and metabolite profiles of pigs and continued to disrupt colonic barrier function by reducing antioxidant capacity via the Nrf2/Keap1 pathway and activating inflammation via the TLR4-NF-κB/ERK pathway during the growing-finishing stage. Colonic Firmicutes and Streptococcus could be potential regulatory targets for modulating the metabolism and health of IUGR pigs.

Oxidoreductase (OXR) enzymes are in high demand for biocatalytic applications in food industry and cosmetics: glucose oxidase (GOx), cellobiose dehydrogenase (CBDH), bioremediation: horseradish peroxidase (HRP), laccase (LAC), and medicine for biosensors and miniature biofuel cells (GOx, CBDH, LAC, HRP). They can be used in a soluble form and/or within the yeast cell walls expressed as chimeras on the surface of yeast cells (YSD), such as P. pastoris and S. cerevisiae. However, most of the current studies suffer from either low yield for soluble enzyme expression or low enzyme activity when expressed as chimeric proteins using YSD. This is always the case in studies dealing with heterologous expression of oxidoreductase enzymes, since there is requirement not only for multiple OXR genes integrations into the yeast genome (super transformations), and codon optimization, but also very careful design of fermentation media composition, and fermentation conditions during expression due to need for adding transition metals (copper, iron), and metabolic precursors of FAD and heme. Therefore, scientists are still trying to find optimal formula using above mentioned approaches, and most recently also using protein engineering and directed evolution for additional increase in the yield of recombinant enzyme production. In this review article we will cover all the current state of the art technologies and most recent advances in the field that yielded high expression level for some of these enzymes in specially designed expression/fermentation systems. We will also tackle and discuss new possibilities for further increase in fermentation yield by the cutting-edge technologies such are directed evolution, protein and strain engineering, high-throughput screening methods based on in vitro compartmentalization, flow cytometry and microfluidics.

Additive Manufacturing (AM) has been proving suitable to support or even replace traditional manufacturing in several industries, offering many advantages such as delivery time and reduction in terms of material waste, energy consumption and greenhouse gas (GHG) emissions. This study aimed to carry out a comparative assessment of the life cycle, from gate to gate, in the production of a low alloy carbon steel flange part using ER-90 wire. The methods utilized were Wire and Arc Additive Manufacturing (WAAM) and conventional manufacturing (CM) by forging, and comparative factors were energy demands, GHG emissions and generated solid waste. The total energy consumption in WAAM was 10,239.40 MJ, total carbon footprint in CO2 equivalent (CO2e) was 714.1 kgCO2e kg-1, and generated solid waste was 68.6 kg, respectively, 90%, 95% and 76% lower than consumption calculated in conventional manufacturing.

Nowadays, brain signal processing is performed rapidly in various brain-computer interface (BCI) applications. Most researchers focus on developing new methods for the future or improving the basic implemented models to identify the optimum standalone feature set. Our research focuses on four ideas. One of them introduces future communication models, and the others are for improving old models or methods. These are: 1) new communication imagery model instead of speech imager using the mental task: Due to speech imagery is very difficult, and it is impossible to imagine sound for all of the characters in all of the languages. Our research introduces a new mental task model for all languages that call Lip-sync imagery. This model can use for all characters in all languages. This paper implemented two lip-sync for two sounds, characters or letters. 2) New combination Signals: Selecting an inopportune frequency domain can lead to inefficient feature extraction. Therefore, domain selection is so important for processing. This combination of limited frequency ranges proposes a preliminary for creating Fragmentary Continuous frequency. For the first model, two s intervals of 4 Hz as filter banks were examined and tested. The primary purpose is to identify the combination of filter banks with 4Hz (scale of each filter bank) from the 4Hz to 40Hz frequency domain as new combination signals (8Hz) to obtain well and efficient features using increasing distinctive patterns and decreasing similar patterns of brain activities.3) new supplement bond graph classifier for SVM classifier: When SVM linear uses in very noisy, the performance is decreased. But we introduce a new bond graph linear classifier to supplement SVM linear in noisy data. 4) a deep formula recognition model: it converts the data of the first layer into a formula model (formula extraction model). The main goal is to reduce the noise in the subsequent layers for the coefficients of the formulas. The output of the last layer is the coefficients selected by different functions in different layers. Finally, the classifier extracts the root interval of the formulas, and the diagnosis does based on the root interval. For all of the ideas achieved the results of implementing methods. The results are between 55% to 98%. Less result is 55% for the deep detection formula, and the highest result is 98% for new combination signals.

Disturbed metabolism of vitamins B1 or B6, which are essential for neurotransmitters homeostasis, may cause epilepsy. Our study aims at revealing therapeutic potential of vitamins B1 and B6 in epilepsy by estimating effects of their combined administration on a seizure and its consequences in rats subjected to pentylenetetrazole (PTZ). The PTZ dose dependence of a seizure and its parameters according to Racine’s scale along with delayed physiological and biochemical consequences next day after the seizure are assessed regarding sexual dimorphism in epilepsy. PTZ sensitivity is stronger in the female than male rats. Next day after a seizure, gender differences in behavior and brain biochemistry arise. The induced gender differences in anxiety, exploratory and locomotor activity correspond to disappearance of gender differences in the brain GABA, aspartate, alanine and serine, with appearance of those in glutamate, glutamine and tyrosine. PTZ decreases the brain malate dehydrogenase activity, glutamine and urea in the males, and phenylalanine in the females. Administration of vitamins B1 and B6 24 h before PTZ delays a seizure in female rats only. This desensitization is not observed at short intervals (0.5-2 h) between the vitamins and PTZ administration. With the increasing interval, the pyridoxal kinase (PLK) activity in the female brain decreases, suggesting that the PLK downregulation by vitamins contributes to the desensitization. Delayed effects of vitamins and/or PTZ are mostly gender-specific and interacting. Our findings on the gender differences in sensitivity to epileptogenic factors, action of vitamins B1/B6 and associated biochemical events have medical implications.

Vitamin D, sunshine and UVB phototherapy were first reported in the early 1900s to control psoriasis, cure rickets and cure tuberculosis (TB). Vitamin D also controlled asthma and rheumatoid arthritis with intakes ranging from 60,000 to 600,000 International Units (IU)/day. In the 1980s interest in treating psoriasis with vitamin D rekindled. Since 1985 four different oral forms of vitamin D (D2, D3, 1-hydroxyvitaminD3 (1(OH)D3) and 1,25-dihydroxyvitaminD3 (calcitriol)) and several topical formulations have been reported safe and effective treatments for psoriasis—as has UVB phototherapy and sunshine. In this review we show that many pre-treatment serum 25(OH)D concentrations fall within the current range of normal, while many post-treatment concentrations fall outside the upper limit of this normal (100 ng/ml). Yet, psoriasis patients showed significant clinical improvement without complications using these treatments. Current estimates of vitamin D sufficiency appear to underestimate serum 25(OH)D concentrations required for optimal health in psoriasis patients, while concentrations associated with adverse events appear to be much higher than current estimates of safe serum 25(OH)D concentrations. Based on these observations, the therapeutic index for vitamin D needs to be reexamined in the treatment of psoriasis and other diseases strongly linked to vitamin D deficiency, including COVID-19 infections, which may also improve safely with sufficient vitamin D intake or UVB exposure.

A new cocrystal salt of metformin, an antidiabetic drug, and N,N’-(1,4-phenylene)dioxalamic acid, was synthesized by mechanochemical synthesis, purified by crystallization from solution and characterized by single X-ray crystallography. The structure revealed a salt-type cocrystal composed of one dicationic metformin unit, two monoanionic units of the acid and four water molecules namely H2Mf(HpOXA)2∙4H2O. X-ray powder, IR, 13C-CPMAS, thermal and BET adsorption-desorption analyses were performed to elucidate the structure of the molecular and supramolecurar structure of the anhydrous microcrystalline mesoporous solid H2Mf(HpOXA)2. The results suggest that their structures, conformation and hydrogen bonding schemes are very similar between them. To the best of our knowledge, the selective formation of the monoanion HpOXA⁻, as well as its structure in the solid, is herein reported for the first time. Regular O(-)∙∙∙C(), O(-)∙∙∙N+ and bifacial O(-)∙∙∙C()∙∙∙O(-) of n→* charge-assisted interactions are herein described in H2MfA cocrystal salts which could be responsible of the interactions of metformin in biologic systems. The results, support the participation of n→* charge-assisted interactions independently, and not just as a short contact imposed by the geometric constraint due to the hydrogen bonding patterns.

Background: Type 2 diabetes mellitus (T2DM) is associated with increased atherogenicity and inflammatory responses, which may be related to increased levels of high mobility group box 1 (HMGB1) and Dickkopf-related protein 1 (DKK1). Objective: The role of HMGB1 and DKK1 in T2DM is examined in association with lipid and insulin profiles. Methods: Serum HMGB1 and DKK1 were measured in T2DM with and without hypertension and compared with controls. Results: HMGB1 and DKK1 are significantly higher in T2DM irrespective of hypertension. T2DM was also accompanied by increased atherogenicity indices. HMGB1 and DKK1 are significantly correlated with HbA1c, glucose, indices of insulin resistance, β-cell function, and glucose toxicity, and different atherogenic indices. A large part of the variance in the β-cell index (30.5%) and glucose toxicity (34.8%) was explained by the combined effects of HMGB1 and DKK1 and hypertension. We found that 18.3% of the variance of the atherogenic index of plasma was explained by HMGB1 and DKK1 levels and that 31.2% was explained by glucose toxicity, HMGB1 and body weight. Conclusion: The higher serum HMGB1 and DKK1 levels in T2DM patients and the associations with atherogenicity indicate that low grade inflammation and disorders in the Wnt pathways are associated with T2DM and that both HMGB1 and DKK1 may contribute to increased atherogenicity in T2DM. Moreover, both biomarkers may cause more deficits in β-cell function and increase glucose toxicity leading to the development of more inflammation and diabetic complications. HMGB1 and the Wnt pathways are new drug targets in the treatment of T2DM.

Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome - Coronavirus-2) of the family Coronaviridae, appeared in Wuhan, Hubei province, China being its epicenter in December 2019. This disease was declared as posing Public Health International Emergency by World Health Organization on January 30, 2020, attained the status of a very high-risk category on February 29, and now having a pandemic status (March 11, 2020). COVID-19 has presently spread to more than 195 countries/territories while killing nearly 19,600 humans out of cumulative confirmed cases accounting to more than 430,000 within a short period of just a few weeks. The majority of deaths have been reported in Italy and China. Researchers worldwide are pacing with high efforts to counter the spread of this virus and to design effective vaccines and therapeutics/drugs. Few of the studies have shown the potential of animal-human interface and zoonotic links in the origin of SARS-CoV-2. Exploring the possible zoonosis and revealing the factors responsible for its initial transmission from animals to humans will pave ways to design and implement effective preventive and control strategies to counter COVID-19. The present review presents an overview of COVID-19 and the causative virus SARS-CoV-2, with particular emphasis on the role of animals and their jumping the cross-species barriers, experiences learned from SARS- and MERS-CoVs, zoonotic links, and spillover events, transmission to humans and rapid spread., highlighting in very brief the preventive and control measures along with a few of the recent research developments to counter this pandemic virus/disease.

Rationale: Major depressive disorder (MDD) is characterized by signaling aberrations in interleukin (IL)-6, IL-10, beta-endorphins as well as mu (MOR) and kappa (KOR) opioid receptors. Here we examined whether these biomarkers may aid in the classification of unknown subjects into the target class MDD.Methods: The aforementioned biomarkers were assayed in 60 first-episode, drug-naïve depressed patients and 30 controls. We analyzed the data using joint principal component analysis (PCA) performed on all subjects to check whether subjects cluster by classes; support vector machine (SVM) with 10-fold validation; and linear discriminant analysis (LDA) and SIMCA performed on calibration and validation sets and we computed the figures of merit and learnt from the data. Results: PCA shows that both groups were well separated using the first three PCs, while correlation loadings show that all 5 biomarkers have discriminatory value. SVM and LDA yielded an accuracy of 100% in validation samples. Using SIMCA there was a highly significant discrimination of both groups (model-to-model distance=87.5); all biomarkers showed a significant discrimination and modeling power, while 10% of the patients were identified as outsiders and no aliens could be identified.Discussion: We have delineated that MDD is a distinct class with respect to neuro-immune and opioid biomarkers and that future unknown subjects can be authenticated as having MDD using this SIMCA fingerprint. Precision psychiatry should employ SIMCA a) to authenticate patients as belonging to the claimed target class and identify other subjects as outsiders, members of another class or aliens; and b) to acquire knowledge through learning from the data by constructing a biomarker fingerprint of the target class.

Schizophrenia is characterized by an interrelated activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory reflex system (CIRS), which downregulates the IRS. Deficit schizophrenia is characterized by a deficit in natural regulatory autoimmune responses to tryptophan catabolites. The presence and correlates of IgM isotype antibodies to oxidative specific epitopes (OSEs), nitroso (NO) and nitro (NO₂) adducts in schizophrenia remain unknown.This study measured IgM antibodies to malondialdehyde (MDA), azelaic acid, phosphatidylinositol, oleic acid, NO-tryptophan, NO-albumin, NO-cysteinyl and NO₂-tyrosine in a sample of 80 schizophrenia patients, divided into those with and those without deficit schizophrenia, and 38 healthy controls.Deficit schizophrenia was characterized by significantly lower IgM antibody levels to all OSEs as compared with non-deficit schizophrenia and controls. Lowered IgM antibodies to MDA coupled with increased IgM levels to NO-cysteinyl and NO₂-tyrosine strongly predict deficit schizophrenia versus non-deficit schizophrenia with an area under the ROC curve of 0.913. A large part of the variance (21.2 – 42.2 %) in the negative symptoms of schizophrenia and excitation is explained by IgM antibody titers to MDA (inversely) and NO-cysteinyl and/or NO₂-tyrosine (both positively). Lower IgM antibodies to MDA are significantly associated with impairments in episodic memory including direct and delayed recall.These findings further indicate that deficit schizophrenia is a distinct phenotype of schizophrenia, which is characterized by lower natural IgM antibody levels to OSEs and relative increments in nitrosylation and nitration of proteins. It is concluded that deficits in lowered IgM responses to MDA and azelaic acid (part of the CIRS) attenuate the negative immune-regulatory feedback on the primary immune response and that this process may drive negative symptoms and impairments in episodic memory and thus deficit schizophrenia.

The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose dependent peak viral loads between days 2 and 5 post infection; and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assays lower limit of quantitation and the immune response was insufficient to protect from re-challenge. These results corroborate previous observations but are contrary to reports using other African strains obviating the need for additional studies to elucidate the variables contributing to the disparities. Nonetheless, the utility of an Asian lineage ZIKV IRM model for countermeasures development was verified by vaccinating animals with a formalin inactivated reference vaccine and demonstrating sterilizing immunity against a subsequent subcutaneous challenge.

Background: The patients with head and neck cancer often experience impaired sleep. Moreover, the treatment may negatively affect sleep quality. The aim of this observational study was to evaluate the sleep quality after treatment for head and neck cancer, and its relationship with quality of life and psychological distress. Methods: One hundred fifty-one patients who underwent treatment for head and neck cancer at our department were included in the study. Quality of life, sleep quality, risk of sleep apnea, sleepiness, pain and psychological distress were assessed by means of specific questionnaires. Results: The median follow-up was 30 months. A poor sleep quality was observed in 55.6% of cases. An association between PSQI global sleep quality and EORTC global health status was found. The DT, the HADS anxiety and the HADS depression scores were associated to PSQI global score, sleep quality, sleep latency, sleep disturbances, daytime dysfunction. Conclusions: Sleep disturbances, particularly OSA and insomnia, are frequent in HNC patients, and significantly impact their quality of life and psychological well-being. Given the effect of sleep on overall well-being, addressing sleep disorders should be a priority in the care of HNC patients.

This study aimed to investigate the prevalence of cardiovascular disease (CVD) risk factors among Algerian aircrew, a population exposed to unique environmental and occupational stressors. By comparing these rates to the general population, we sought to identify specific health challenges faced by aircrew. Methods: A cross-sectional study was conducted on 154 Algerian aircrew participants. Prevalence rates for current smoking, hypertension, diabetes, and dyslipidemia were compared between the aircrew and a general population control group. Results: Our findings revealed significantly higher rates of current smoking among aircrew compared to the general population. Additionally, smoking, dyslipidemia, hypertension, and diabetes emerged as the most prevalent risk factors within the aircrew population. Conclusions: Despite the rigorous selection process for aircrew recruitment, our study confirms findings from previous literature, highlighting the high rate of normal qualifying examinations. The substantial sample size and homogeneous nature of the aircrew population enhance the reliability and generalizability of our conclusions. These findings underscore the importance of targeted interventions to mitigate CVD risk factors within this specific population, given the unique environmental and occupational factors associated with aircrew.

We will outline the relationship between luminosity distance and cosmological redshifts, demonstrating that it is consistent with a new cosmological model recently proposed by Haug and Tatum [1], which appears to resolve the Hubble tension within the Rh = ct cosmology.

In today’s business landscape, customer retention has become a critical factor for sustainable growth. Many companies continue to focus on acquisition, which leads to high costs and constant customer turnover. This article highlights the importance of retention, proposing a shift in focus toward loyalty as the key to maximizing customer lifetime value (LTV). Improving retention not only increases LTV but also reduces acquisition costs, enhances virality, and provides financial stability. This paper introduces a scientific approach that allows companies to identify the underlying causes of low retention through observation, hypothesis formulation, and controlled experimentation. Using tools such as data analysis and A/B testing, companies can iteratively optimize their retention strategy, adjusting interventions in real-time based on the results obtained. Continuous experimentation emerges as an indispensable tool for navigating market complexity, enabling organizations to learn and adapt quickly. This data-driven approach not only improves retention but also drives long-term growth by building strong relationships with customers. In an increasingly competitive environment, companies that prioritize retention and experimentation are better positioned to achieve resilient and profitable growth.

The region of Lorraine in France witnessed the collapse of the steel industries in the late twentieth century, causing massive job losses and social devastation. Daewoo Electronics, a division of one of the great Korean conglomerates of the 1980s and 1990s, came to Lorraine in eastern France in 1987. They were lured there by generous French government subsidies and the chance to enter the European market. They opened three factories in consumer electronics and components, and also nearly acquired Thomson Multimédia, a state-owned consumer electronics factory, from the French government “for a single symbolic franc.” The resulting uproar, from political opponents and Thomson and Daewoo employees, ended the deal and soured their relationship with France. Daewoo employed just over a thousand people before they closed in 2003, a result of the collapse of the entire Daewoo Group. This article places this sequence of events, widely covered in the media, in the context of French anxiety about globalization, the loss of industrial substance, and France’s place in a changing world. It is suggested that this episode, occurring at a critical juncture in the transformation of industrial capitalism into a service and digital economy, illustrates the difficulties of this period and the media coverage of factory closings.

Genetic engineering has revolutionized our ability to modify microorganisms for various applications in agriculture, medicine, and industry. This review examines recent advances in genetic engineering techniques for bacteria, fungi, and oomycetes, with a focus on CRISPR-Cas systems. In bacteria, CRISPR-Cas9 has enabled precise genome editing, enhancing applications in antibiotic production and metabolic engineering. For fungi, despite challenges associated with their complex cell structures, CRISPR/Cas9 has advanced the production of enzymes and secondary metabolites. In oomycetes, significant plant pathogens, modified Agrobacterium-mediated transformation and CRISPR/Cas12a have contributed to developing disease-resistant crops. The review provides a comparative analysis of genetic engineering efficiencies across these microorganisms and addresses ethical and regulatory considerations. Future research directions include refining genetic tools to improve efficiency and expand applicability in non-model organisms. This comprehensive overview highlights the transformative potential of genetic engineering in microbiology and its implications for addressing global challenges in agriculture, medicine, and biotechnology.

The circadian clock is an autonomous timekeeping system evolved by organisms to adapt to external changes, regulating a variety of important physiological and behavioral processes. Recent studies have shown that the sirtuin family of histone deacetylases is involved in regulating the expression of clock genes and plays an important role in maintaining the normal rhythm of clock gene expression and behavior. Moreover, sirtuins are regulated directly or indirectly by the circadian clock system. The mutual regulation between the circadian clock and sirtuins is likely involved in a variety of signal transduction and metabolism processes. In this review, we discuss the molecular mechanisms and research progress on the intertwined relationship between the circadian clock and sirtuins, highlighting sirtuins as molecular links between metabolic control and circadian rhythms and offering our perspectives on future developments in the field.

This study examines the relationship between chondroitin sulphate, proteinoids, and computational neuron models, with a specific emphasis on the Izhikevich neuron model. We investigate the effect of chondroitin sulphate-proteinoid complexes on the behaviour and dynamics of simulated neurons. Through the use of computational simulations, we provide evidence that these biomolecular components have the power to regulate the responsiveness of neurons, the patterns of their firing, and the ability of their synapses to change within the Izhikevich architecture. The findings suggest that the interactions between chondroitin sulphate and proteinoid cause notable alterations in the dynamics of membrane potential and the timing of spikes. We detect adjustments in the features of neuronal responses, such as shifts in the thresholds for firing, alterations in spike frequency adaptation, and changes to bursting patterns. The findings indicate that chondroitin sulphate and proteinoids may have a role in precisely adjusting neuronal information processing and network behaviour. This study offers new and valuable information about the complex connection between the many components of the extracellular matrix, protein-based structures, and the functioning of neurons. In addition, our analysis of the proteinoid-chondroitine system using game theory uncovers a significant Prisoner’s Dilemma scenario. The system’s inclination towards defection, due to the appeal of cheating and the significant penalty for cooperation, with a mean voltage of −9.19 mV, indicates that defective behaviors may prevail in the long-term dynamics of these neuronal interactions.

Background and Purpose: Moyamoya disease is a rare cerebrovascular disorder characterized by stenosis of the carotid arteries and the formation of collateral vessels at the base of the brain. While advances have been made in understanding its genetics, diagnostic criteria, and treatment strategies, further research is needed. The purpose of this literature review is to synthesize current knowledge on Moyamoya disease and identify areas for future study. Materials and Methods: A literature search of databases including PubMed, Embase, and Web of Science was conducted. Search terms included "Moyamoya disease" and related terms. Only English articles were reviewed, with no date restrictions. Relevant data was extracted and synthesized. Results: Key findings indicate that genetic factors such as RNF213 variants play an important role in disease susceptibility. Imaging modalities such as MRI and CT angiography are crucial for diagnosis. Surgical revascularization shows superior outcomes compared to medical management for ischemic and hemorrhagic presentations. However, optimal treatment for asymptomatic cases remains unclear. Neurocognitive and psychiatric sequelae can negatively impact quality of life. Promising research directions include investigating ethnic differences, developing biomarkers, and exploring novel therapeutics targeting molecular pathways. Conclusions: In summary, comprehension of Moyamoya disease has significantly progressed but gaps remain regarding treatment of certain populations and underlying mechanisms. Further research addressing these areas can aid in developing personalized care approaches and new interventions to improve patient outcomes

Background and Objectives: The deltopectoral (DP) flap represents a reconstructive option for head and neck. It is a fasciocutaneous flap raised from the anterior chest wall below the clavicle. Its role partially declined with the arise of free flaps. However, it still remains a valid option in patients that could not undergo a reconstruction with free flaps. The aim of this retrospective study was to evaluate the role of the DP flap in head and neck reconstruction, with a focus on surgical outcomes and complications. Materials and Methods: Thirty-one patients who underwent head and neck reconstruction with DP flap were included in the study. The delayed technique was not used in any procedure to harvest the flap beyond the deltopectoral groove. The patients’ characteristics, the recipient site, the closure of the donor site and the flap-related complications were recorded. Results: The median time to autonomization of DP flap was 23 days. Post-operative complications were observed in 10 subjects (32.3%). A partial necrosis was seen in 5 patients (16.1%), while a complete necrosis developed only in one case (3.2%). The diabetes mellitus was the only parameter associated to post-operative complications. In particular, the percentage of necrosis in subjects with or without diabetes was 66.7% and 8.0%, respectively. Conclusions: The DP has a wide range of applications in head and neck reconstruction and a low complication rate can be observed. The delayed technique does not necessarily need to be applied, and the flap can be extended beyond the deltopectoral groove when necessary. However, patients with diabetes mellitus have a higher risk of postoperative necrosis of the distal portion of the flap.

This article introduces a new interpretation to Socialism that approaches it via a heuristic study of Epochs. It is intended by this study that the intention of socialism (what it politically, socially, et cetera is proclaimed to be) is to be proposed to be indeterminate.The expectation of what Socialism is to be as a future entity is merely an interpretation that is predicated on Marx’s Capitalist Laws that have been since shown to be false. Its argument is suggested significantly by Engels’ discussions of human development and therein places an added focus on a historically based platform.

The implementation of cybersecurity standards and directives in the maritime sector plays a crucial role in protecting critical maritime infrastructures from cyber threats. The level of protection depends heavily on humans. However, the effectiveness of cybersecurity training and compliance programs, an essential component of these standards, is often hindered by challenges related to the sector’s environment, including the established technologies, practices, and norms. This paper aims to identify these challenges through a literature review and set the basis for more effective human risk minimisation, responses, and training. We identify 18 challenges and validate them with an online survey (N=205) capturing real-world perspectives from maritime-related stakeholders. Our findings contribute to enhancing the effectiveness of maritime cybersecurity training and compliance programs, ultimately strengthening the maritime cybersecurity posture.

Whole grain consumption in the US has increased due to the introduction of whole grains initially in breakfast cereals and then in snacks. Most people consider fiber as the health benefit of eating whole grains since it inhibits the absorption of fats and sugar in the GI tract. Polyphenols, the major antioxidants in the US diet, are primarily covalently bound to the fiber matrix of grains that are broken during digestion. Human biomarkers have been found after cereal grain consumption, thus proving bioavailabilty of polyphenols. Savory snacks (n=32) studied included potato chips, tortilla chips, pretzels and crackers. The snacks contained as the first ingredient enriched wheat, whole wheat, corn, potatoes, and beans. We have used both a Folin and ferric reducing antioxidant power (FRAP) colorimetric method with catechin as the standard for the commercial snack assays. Total polyphenols were analyzed after basic hydrolysis. Maximum bio-accessible polyphenols were measured after sample hydrolysis simulating in vivo digestion. FRAP measurements were done on the same samples. FRAP total antioxidant capacity values were significantly higher than Folin total polyphenols but followed the same trends and were highly correlated. Digestion significantly decreased both polyphenols and antioxidant capacity. Whole grain snacks, defined as having &gt; 50% whole grains, had significantly more polyphenols (7 times) than enriched grain snacks. Savory snack Folin polyphenols after in vitro digestion averaged 64% of the total polyphenol value. This indicates polyphenol bio-accessibility might be favorable after snack consumption. Using published data and this work, the order of total polyphenols in all snacks is nuts &gt;&gt; dried fruits &gt; popcorn &gt; pretzels &gt; tortilla chips &gt; crackers &gt; potato chips. Potato chips are the most consumed snack but are lowest in polyphenols antioxidants.

Tropical regions face significant energy challenges due to climatic conditions. This study investigates the interplay between sustainable architecture and building energy regulations in mitigating these challenges. The study aims to assess the effectiveness of existing building energy regulations in promoting sustainable architecture in tropical climates and identify key architectural strategies and regulatory frameworks for optimizing energy efficiency in tropical buildings. A comparative analysis of building regulations and case studies of sustainable buildings in selected tropical regions is conducted. The findings reveal that current regulations often must be revised to address tropical climates' unique energy demands. Incorporating passive design principles, renewable energy systems, and material selection is crucial for energy efficiency. It is recommended that building energy regulations be strengthened to mandate sustainable design strategies and provide incentives to promote the adoption of energy-efficient technologies.

Tropical regions face unique challenges in building sustainability due to high temperatures, humidity, and heavy rainfall. While building energy regulations are essential for promoting energy efficiency, their effectiveness in addressing tropical climate conditions needs to be studied more. This research aims to systematically investigate tropical building sustainability issues and evaluate the impacts of building energy regulations on these challenges. The study will identify gaps in current regulations by analyzing existing research and recommend strategies for developing more comprehensive frameworks that promote sustainable building practices in tropical regions. This research contributes to developing effective policies and strategies for achieving sustainable and energy-efficient built environments in tropical climates.

The design of school environments plays a pivotal role in promoting student wellness, mindfulness, and socio-emotional learning (SEL). This article explores the integration of Environment Behaviour Studies (EBS) concepts into school design to enhance students' overall well-being and academic success. It highlights the importance of indoor environmental quality, ergonomic and flexible learning spaces, and biophilic design in fostering a healthy and engaging learning atmosphere. Additionally, the article delves into the creation of mindfulness spaces, sensory-friendly environments, and the use of colour and aesthetics to support emotional regulation and mental health. By examining case studies of successful implementations, the article underscores best practices for designing schools that promote positive social interactions, ensure safety, and reflect community values. Ultimately, this comprehensive approach to school design aims to nurture holistic development, support socio-emotional learning, and prepare students for lifelong success.

I present a personal account of self-organizing systems. As such, it is necessarily biased and partial. Nevertheless, it should be useful to motivate useful discussions. The relevant contribution is not my attempts at answering questions (maybe all my answers are wrong), but the steps towards framing relevant questions to better understand self-organization, information, complexity, and emergence. With this aim, I start with a notion and examples of self-organizing systems (what?), continue with their properties and related concepts (how?), and close with applications (why?).

Drug repositioning is an efficient strategy to search for new treatment alternatives that is especially valuable for neglected parasitic diseases such as leishmaniasis. Tamoxifen and raloxifene are selective estrogen receptor modulators (SERM) that have shown antileishmanial activity. Clomiphene is a SERM structurally similar to tamoxifen whose antileishmanial potential is unknown. That is why the objective of the present work was to evaluate its antileishmanial activity in vitro and in vivo, in comparison with tamoxifen. The inhibitory effect against promastigotes of L. amazonensis, L. major and L. mexicana was evaluated for both compounds; as well as the cytotoxicity against mouse peritoneal macrophages, the growth inhibitory activity in intracellular amastigotes of L. mexicana, and the in vivo activity in mice experimentally infected with L. mexicana. Clomiphene was about twice as active as tamoxifen against both promastigotes and intracellular amastigotes, with IC50 values of 1.7-3.3 µM for clomiphene and 2.9-6.4 µM for tamoxifen against all three species promastigotes; and 2.8 ± 0.2 µM and 3.7 ± 0.3 µM, respectively, against L. mexicana amastigotes. Clomiphene structurally affected several parasite organelles in a concentration-dependent fashion, leading to the death of both promastigotes and intracellular amastigotes. Interestingly, the macrophage host cell did not appear damaged with any of the clomiphene concentrations tested. By oral administration at 20 mg/kg for 14 days, both compounds showed similar effects in terms of reducing the growth of the lesions, as well as the weight of the lesions and the parasite load at the end of the follow-up period. The results showed the potential of SERM as antileishmanial drugs and support further testing of clomiphene and other compounds of this pharmacological group.