Objective: We report a case of acute pancytopenia and liver injury after concomitant administration of low-dose methotrexate (MTX), and high-dose esomeprazole and metamizole. Case summary: A 71-year-old patient with chronic systemic idiopathic erosive arthritis was admitted after a pelvic ring fracture. After hospital admission, she received MTX in addition to esomeprazole and metamizole. Subsequent laboratory tests revealed pancytopenia and elevated liver enzymes. The follow-up clinical examinations were unremarkable, with the exception of sub-febrile temperatures. Further investigations did not detect a definitive etiology. Due to the suspicion of methotrexate-induced hematotoxicity and hepatotoxicity, antagonizing therapy with calcium folinate was administered, after which the blood counts and liver parameters normalized. Discussion: Due to the administration of high-dose metamizole immediately before the administration of low-dose MTX, the pre-existing hematotoxic pharmacodynamic effect of MTX was acutely enhanced by that of metamizole, although folic acid was administered preemptively. In addition, the concomitant administration of high-dose esomeprazole and normal dose torasemide resulted in a pharmacokinetic interaction with MTX by decreasing its renal secretion and elimination, further enhancing the concentration-dependent hematotoxic and hepatotoxic side effects of MTX. Conclusions: The relatively high demand for analgesics in patients with chronic rheumatic diseases already being treated with MTX and proton pump inhibitors necessitates that clinicians consider drug-drug interactions as potential causes of adverse drug reactions after the administration of metamizole or nonsteroidal anti-inflammatory drugs. In this category of patients, it is strongly recommended to switch to analgesics of other classes.

Flomoxef (FMX) may be a potential alternative to carbapenems for dogs infected with Enterobacterales producing extended-spectrum β-lactamase (ESBL-E). However, the appropriate dosage of FMX in dogs with ESBL-E infections has yet to be established. This study was carried out to establish appropriate treatment regimens for FMX against ESBL-E infections in dogs by a pharmacokinetics–pharmacodynamics (PK–PD) approach. Five dogs received an intravenous bolus dose of FMX (40 mg/kg). Serum FMX concentrations were evaluated using high-performance liquid chromatography-tandem mass spectrometry, and PK indices were determined based on non-compartmental model. The cumulative fraction of response (CFR) was calculated based on the distribution of minimum inhibitory concentrations among wild-type ESBL-E from companion animals. As the results, the dosage regimens of 40 mg/kg q8h and q6h were estimated to achieve a CFR of >90% for wild-type isolates of ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis for dogs. In contrast, all regimens exhibited a CFR of <80% for ESBL-producing Enterobacter cloacae. Our results indicated that dosage regimens of 40 mg/kg FMX q8h and q6h can be a non-carbapenem treatment for dogs infected with ESBL-producing isolates of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, but not for those infected with ESBL-producing Enterobacter cloacae.

Quantum correlations, especially time correlations, are crucial in ghost imaging in order to significantly reduce the background noise on the one hand while increasing the imaging resolution. Moreover, the time correlations serve as a critical reference, distinguishing between signal and noise, which in turn enable clear visualization of biological samples. Quantum imaging also addresses the challenge involved in imaging delicate biological structures with minimal photon exposure and sample damage. Here we explore the recent progress in quantum correlation-based imaging, notably its impact on secure imaging and remote sensing protocols as well as on biological imaging. We also exploit the quantum characteristics of heralded single-photon sources (HSPS) combined with decoy-state methods for secure imaging. This method uses Quantum Key Distribution (QKD) principles to reduce measurement uncertainties and protect data integrity. It is highly effective in low-photon-number regimes for producing high-quality, noise-reduced images. The versatility of decoy-state methods with WCSs (WCS) is also discussed, highlighting their suitability for scenarios requiring higher photon numbers. We emphasize the dual advantages of these techniques: improving image quality through noise reduction and enhancing data security with quantum encryption, suggesting significant potential for quantum imaging in various applications, from delicate biological imaging to secure quantum communication.

Aerobic vaginitis (AV) is a distinct clinical entity characterized by inflammation and abnormal vaginal microflora. Often mistaken for bacterial vaginosis, AV remains relatively unknown and underdiagnosed. AV's understanding is evolving, with some experts suggesting it may primarily be an immunological disorder, the prevalence of which ranges from 7-13% in non-pregnant women and 4.1-8.3% during pregnancy. Pregnancy can affect susceptibility to vaginal infections, leading to adverse outcomes for the woman and the newborn. This review summarizes the correlation between AV and adverse pregnancy outcomes, particularly preterm birth, the leading cause of morbidity and mortality among neonates. Improved understanding of AV's impact on pregnancy outcomes can lead to early recognition, proper management, and effective interventions. While some studies support an association between AV and preterm labor, the existing knowledge of this relationship remains limited. The evidence suggests that AV may contribute to adverse pregnancy outcomes, mainly preterm birth, but further research is needed to establish a definitive link. Further studies are needed to investigate the underlying mechanisms and clarify AV's role in premature labor. A comprehensive understanding of AV's impact on pregnancy outcomes is crucial for early recognition, appropriate management, and effective interventions.

Ten new Schiff bases, including thiocarbohydrazone derivatives (1–10), were synthesized using an efficient, uncomplicated, and environmentally friendly approach using the reaction of alkyl-substituted aldehydes. The thiocarbohydrazones that were obtained were derived from o-phthalaldehyde. The chemical structures of the compounds were identified by the utilization of UV-Vis spectroscopy, Fourier transform infrared (FT-IR), ¹H nuclear magnetic resonance (¹H NMR), ¹³C nuclear magnetic resonance (¹³C NMR), and elemental analysis methods. The thermal stability of thiocarbohydrazones was examined using thermogravimetric analysis (TGA-DSC). Investigations were conducted on urease inhibition tests, pharmacokinetic property research, and molecular docking. The collection of samples with the urease enzyme revealed significant molecular docking findings, with MolDock scores ranging from -153 to -189. The compounds have the potential to be effective drug candidates for treating certain diseases, as indicated by the consistent results of molecular docking, urease inhibition tests, and pharmacokinetic characteristics investigations.

Not occasional phamracokinetic variability and suboptimal exposure have been reported for micafungin in the intensive-care-unit (ICU) patients. This study aims to evaluate the quality of population pharmacokinetic models and provide rational using recommendation of this drug in clinical practice. Monte Carlo simulations were implemented to compare pharmakinetic parameters and probability of target attainment (PTA) towards various Candida species. Body weight, liver function, and SOFA score were the most frequent covariates in the final 16 included studies. micafungin clearance for ICU adults (SOFA≥10 or <10) was 39%–52% and 43%–57% higher, respectively, than non-ICU adults. For Candida infections with MICs <0.016 mg/L, the ICU group had lower proportions achieving PTA > 90% compared to the non-ICU group (2/6 (33%) vs. 4/7 (57%)), and for non-ICU and ICU adults, micafungin dosages of 100 and 150 mg were recommended, respectively. While for C. tropicalis and C. glabrata, 200 and 250 mg were recommended respectively. However, for C. krusei and C. parapsilosis, it failed to reach assumed PTA at MICs of 0.125-0.25 mg/L and 0.125-2 mg/L, respectively. Adjusting micafungin dosage in ICU patients may be necessary. Both ICU and non-ICU adults should modify their dosage regimens based on the Candida species and their respective MICs.

Few-shot object detection (FSOD) aims to address the challenge of requiring a substantial amount of annotations for training in conventional object detection, which is very labor-intensive. However, existing few-shot methods achieve high precision with the sacrifice of time-consuming for exhaustive fine-tuning, or take poor performance in novel-class adaptation. We presume the major reason is that the valuable correlation feature among different categories is insufficiently exploited, hindering the generalization of knowledge from base to novel categories for object detection. In this paper, we propose Few-Shot object detection via Correlation-RPN and Transformer Encoder-Decoder (CRTED), a novel training network to learn object-relevant features of inter-class correlation and intra-class compactness while suppressing object-agnostic features in the background with limited annotated samples. And we also introduce a 4-way tuple-contrast training strategy to positively activate the training progress of our object detector. Experiments over two few-shot benchmarks (Pascal VOC, MS-COCO) demonstrate that, our proposed CRTED without further fine-tuning can achieve comparable performance with current state-of-the-art fine-tuned works. The codes and pre-trained models will be released.

Dynamic time history analysis is a powerful and effective method to study the seismic response of tunnels, the dynamic time history to analyze the seismic response of the tunnel in the typical subway in this paper. The analysis results show that the overall levelling of the tunnel will not affect the tunnel too much, and the seismic response of the tunnel is mainly related to the relative displacement of the ground around the tunnel. The analysis results show that the internal force of the tunnel and the tunnel inclination have a good linear relationship, and the tunnel inclination can be used to measure the magnitude of the seismic response of the tunnel.

Background: Gender stereotypes and biases can influence perceptions of competence and suitability for certain medical specialties. Empathy is an important component of an optimal doctor-patient relationship. The scope of our study is to verify the correlation between “empathetic" behavioral style with attention and sensibility to the gender differences of patients of the medical students. Methods: An online survey was conducted using the Jefferson Scale for Empathy (JSE), to measure empathy in the context of health professions education and patient care; and the Nijmegen Gender Awareness in Medicine Scale (N-GAMS), which measures attitudes and assumptions about gender. A total of 234 students (52.1% M; mean age: 22.68±2.48) from Medicine and Surgery at the University of Salerno (Italy) participated, of whom n° 175 were third-year students and n° 59 were fifth-year students. Results: The JSE score shows that male students have higher scores (77.29±12.38) than females (75.91±10.39). Conversely, female students have higher perspective-taking (JSE Factor 1: Male= 51.26±11.84; Female= 52.72±11.88). In addition, third-year students are much more empathetic than their fifth-year colleagues (JSE Score: 3°ys= 77.35±11.46; 5°ys= 74.49±11.33). With reference to the GS, we found that male students have greater sensitivity than their female colleagues (GS: Male= 2.67±0.68; Female= 2.37±0.48); conversely, they have higher scores of gender stereotype towards patients (GRIP: Male= 2±0.88; Female= 1.59±0.61) and doctors (GRID: Male= 1.88±0.89; Female= 1.64±0.63). Also, the third-year students compared to their fifth-year colleagues are characterized by greater gender sensitivity (GS: 3°ys= 2.57±0.62; 5°ys= 2.42±0.57), less bias with respect to patients (GRIP: 3°ys= 1.77±0.79; 5°ys= 1.90±0.78) but, on the other hand, show more stereotypes and prejudices towards doctors (GRID: 3°ys= 1.77±0.81; 5°ys= 1.75±0.74). Conclusions: Humanistic attitudes, including empathy, should be instilled, and evaluated among trainees as an essential part of their postgraduate medical education.

Background: Clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords "clozapine" and "schizophrenia," "side effects," "agranulocytosis," "TRS," or "bipolar affective disorder (BAF)" for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: We selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: We considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) Clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions' severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together. Background: Clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords "clozapine" and "schizophrenia," "side effects," "agranulocytosis," "TRS," or "bipolar affective disorder (BAF)" for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: We selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: We considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) Clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions' severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together.

1) Background- Coronary artery bypass grafting (CABG) is a common surgical intervention for patients with severe coronary artery disease. The Model for End-Stage Liver Disease (MELD) score has been widely used to predict mortality risk in patients with end-stage liver disease, but its utility in predicting postoperative outcomes in cardiac surgery patients is less well-established. 2) Methods-This retrospective study aims to investigate the association between preoperative MELD score and post-operative complications, length of hospital stay, and mortality in patients under-going coronary artery bypass grafting. This is a single-center, retrospective cohort study conducted at a tertiary care academic medical center. The study includes all adult patients who underwent elective coronary artery bypass grafting between January 2011 and December 2020. Preoperative MELD scores were calculated for each patient, and postoperative outcomes including major ad-verse cardiac events, length of hospital stay, and 30-day mortality was assessed. To ensure a homogeneous study cohort, we excluded patients who underwent emergent cardiac procedures or had incomplete data necessary for the calculation of MELD scores and assessment of postoperative outcomes. Data was extracted from the electronic medical records, including patient de-mographics, comorbidities, preoperative laboratory values, operative details, and postoperative outcomes. The study protocol was approved by the Institutional Review Board, and the require-ment for informed consent was waived due to the retrospective nature of the study.3) Results- This study reveals a statistical association between the MELD score calculated at admission and the length of hospital stay, duration in the ICU, patient age, and the duration of aortic clamping and extracorporeal circulation. Specifically, there is an exponential increase in the MELD score corre-lating with the rise in these factors, both collectively and individually, highlighting a significant relationship between the duration of extracorporeal circulation and aortic clamping time. 4) Conclusion-Patients with a high MELD score had an increased risk of postoperative complications and mortality compared to those with a low MELD score. Careful preoperative patient selection and optimization of the patient's clinical condition may improve outcomes in patients with advanced liver disease undergoing cardiac surgery.

We recently reported the isolation and characterization of an anti-SARS-CoV-2 antibody, called IgG-A7, that protected transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE-2) from the infection with SARS-CoV-2 Wuhan. We show here that IgG-A7 protected 100% of the transgenic mice infected with Delta (B.1.617.2) and Omicron (B.1.1.529) at doses of 0.5 and 5 mg/kg, respectively. In addition, we studied the pharmacokinetic (PK) profile and Toxicology (Tox) of IgG-A7 in CD-1 mice at single doses of 100 and 200 mg/kg. PK parameters at those high doses were proportional to the dose, with the half-life in serum of ~10.5 days. IgG-A7 was well tolerated with no signs of toxicity in urine and blood samples, nor in histopathology analyses. Tissue Cross-reactivity (TCR) with a panel of mouse and human tissues showed no evidence of IgG-A7 interaction with tissues of these species, supporting the PK/Tox results in vivo and suggesting that while IgG-A7 has a broad efficacy profile it is not toxic in humans. The information generated in CD-1 mouse as PK/Tox model, complemented with the mouse and human TCR, could be of relevance as alternatives to NHPs in rapidly emerging viral diseases and/or quickly evolving viruses such as SARS-CoV-2.

Bridges enable communications and transportation of goods nationally and internationally, underpinning economic and social activities, thus they are pylons of our prosperity and mobility. Bridges worldwide are constantly subjected to physical wear, ageing, deterioration, hazards, environmental influences, and increased loading. Loss of performance and functionality of bridge structures would have a crucial impact on overall infrastructural resilience and would cause significant negative economic and social consequences. Monitoring their behaviour for different loading conditions relies on accurate estimations of the stress-strain state of various critical components and remaining capacities. These activities are of high importance for better planning lifespan prolongation, that is the extension of their service life and prevention of unforeseen collapses, in line with sustainability principles of well-informed maintenance. In many cases, access to the structure is limited or even impossible, which causes the need for the deployment of remote and contactless methods. One such innovative technique, which has recently attracted attention in scientific and practical applications is the digital image correlation (DIC). DIC is a contactless approach applicable for long-term measurements, which enables obtaining the full field of strains and deformations. Although the DIC approach has been widely used in world engineering practice for monitoring bridges and has proved to be a reliable and accurate method, there is a lack of systematic integral review on previous practical applications, revealing limitations and perspectives. This is the main motivation and novelty of this study, which will describe selected case studies, in which DIC was used on real full-scale bridge structures and propose improvements for the method.

The intestinal microbial community of aquatic animals is closely related to the environment and thus affects the health of aquatic animals. Here we investigated annual variation of intestinal bacteria community structures of Ruditapes philippinarum cultured using two different methods, bottom sown and raft hanging. Bacterial diversity of seawater and sediment in different seasons was examined as well. Correlation between R. philippinarum intestinal bacteria community structures and environmental factors was analyzed. The results showed that in the two aquculture areas where R. philippinarum was differentially cultured, bacteria community structure of seawater and sediment both altered with seasons. However, neither seasonal changes nor difference in culture methods could significantly affect the intestinal bacteria community structures of R. philippinarum. Additionally, in terms of the alpha diversity of intestinal bacteria communities, there was no significant difference in R. philippinarum cultured using the two methods. For benthic cultured clams, alpha diversity of the intestinal bacterial communities was often higher than that of the environmental bacterial communities. For raft hanging cultured calms, Alpha diversity of the intestinal bacterial communities was normally comparable with that of the environmental counterparts. Beta diversity analysis showed that the intestinal bacterial community structure of R. philippinarum was mainly determined by both deterministic and stochastic processes. Correlation analysis showed that the intestinal bacterial community structures of R. philippinarum were determined by a variety of environmental factors. For clams collected from the benthic culture area, the intestinal bacterial structure was more correlated with the physicochemical properties of sediment in comparing with those of seawater. For clams collected from the raft-culture area, the intestinal bacterial structure was mainly determined by the phsicochemical characteristics of seawater. This study helps us to better understand the bacterial community structure in complex aquaculture ecosystems, providing a reference for healthy shellfish aquaculture and ecosystem protection in aquaculture area.

Flavonoids comprise a large group of structurally diverse polyphenolic compounds of plant origin and are abundantly found in human diet such as fruits, vegetables, grains, tea, dairy products, red wine and so on. Major classes of flavonoids include flavonols, flavones, flavanones, flavanols, anthocyanidins, isoflavones, and chalcones. Owing to their potential health benefits and medicinal significance, flavonoids are now considered as an indispensable component in a variety of medicinal, pharmaceutical, nutraceutical, and cosmetic preparations. However, flavonoids play a significant role in preventing cardiovascular diseases (CVDs), which could be mainly due to their antioxidant, antiatherogenic, and antithrombotic effects. Epidemiological and in vitro/in vivo evidences of antioxidant effects support the cardioprotective function of dietary flavonoids. Further, the inhibition of LDL oxidation and platelet aggregation following regular consumption of food containing flavonoids and moderate consumption of red wine might protect against atherosclerosis and thrombosis. A study suggests that daily intake of 100 mg of flavonoids through diet may reduce the risk of developing morbidity and mortality due to coronary heart disease (CHD) by approximately 10%. This review summarizes dietary flavonoids with their sources and potential health implications in CVDs including various redox-active cardioprotective (molecular) mechanisms with antioxidant effects. Pharmacokinetic (oral bioavailability, drug metabolism), toxicological and therapeutic aspects of dietary flavonoids are also addressed herein with future directions for the discovery and development of useful drug candidates/ therapeutic molecules.

Kaempferia parviflora Wall. ex Baker (KP), Krachaidam in Thai or Thai ginseng, is an herbal medicine that has many potential pharmacological effects. This study focused on the oral glucose tolerance test and pharmacokinetic study in healthy volunteers administered with KP extract (90 and 180 mg/day, placebo). The oral glucose tolerance tests were performed at baselines and 28-days of administration. The pharmacokinetics were determined after a single dose administration of the tested products using 3,5,7,3,4-pentamethoxyflavone (PMF) and 5,7,4-trimethoxylfavone (TMF) as markers. The results showed that glucose metabolism via oral glucose tolerance test was not affected by KP extract. The results of pharmacokinetics study revealed that only TMF and PMF, but not DMF levels could be detected in human blood. The given doses of KP extract at 90 and 180 mg/day showed a linear dose-relationship of blood PMF concentration whereas blood TMF was detected only at high given dose (180 mg/day). The half-lives of PMF and TMF were 2–3 h. The Cmax, AUC and Tmax values of PMF and TMF estimated for the 180 mg/day dose were 85.3711.31, 73.2329.93 mg/ml; 291.8948.23, 412.20203.69 mg.h/ml; and 3.890.37, 4.500.96 h, respectively. PMF was quickly eliminated with higher Ke and Cl than TMF at the dose of 180 mg/day of KP extract. In conclusion, the results demonstrated that KP extract had no effect on glucose tolerance test. In addition, this is the first demonstration of the pharmacokinetic parameters of methoxyflavones of KP extract in healthy volunteers in a phase I study in drug development. The data suggest the safety of the KP extract and will be of benefit for further clinical trials using KP extract as food and sport supplements as well as a drug in health product development.

Bicycle transport stands at the forefront of sustainable mobility initiatives, a cornerstone of European Union policy. While support for cycling is crucial, its advancement hinges upon the presence of high-quality, secure infrastructure for cyclists. Safety emerges as a paramount concern, influencing the viability of cycling as a mode of transportation, yet its perception varies among user demographics. Considering this, this article endeavours to examine and contrast cycling infrastructure across various European nations, alongside analysing statistics pertaining to fatal traffic accidents involving cyclists. In our paper, we have chosen the Netherlands as a representative of building quality cycling infrastructure with many years of experience, and two countries that are developing conditions for cyclists, Slovakia and Poland. We have applied a correlation between the length of the transport infrastructure and the number of cyclists killed. The findings point to the substantial correlation between the quality of cycling infrastructure and the incidence of accidents. This correlation underscores the pressing need for robust infrastructure development and safety measures to bolster cycling as a safe and viable transportation option. We have employed the Shapiro-Wilk test for normal distribution to verify the input data and process the Pearson correlation to investigate the correlation between cycling infrastructure and road accident fatalities of cyclists.

Febuxostat (FBX), a selective xanthine oxidase inhibitor, belongs to BCS class II showing low solubility and high permeability with a moderate F value (< 49%). Recently, FBX/L-pyroglutamic acid cocrystal (FBX-PG) was developed with improving 4-fold increase of the FBX solubility. Nevertheless, in vivo pharmacokinetic property of FBX-PG has not been evaluated yet. Therefore, the pharmacokinetic feasibility of FBX in FBX and FBX-PG-treated rats and mice was compared in this study. The results showed that the F values of FBX were 210% and 159% in FBX-PG rats and mice, respectively. The 2.10-fold greater AUC of FBX was due to the increased absorption (i.e., 2.60-fold higher Cmax,1 at 15 min) and entero-hepatic circulation of FBX (i.e., 1.68-fold higher Cmax,2 at 600 min) in FBX-PG rats compared to the FBX rats. The 1.59-fold greater AUC of FBX was due to a 1.65-fold higher Cmax,1 at 5 min, and 1.15-fold higher Cmax,2 at 720 min of FBX in FBX-PG mice than those in FBX mice. FBX was highly distributed in the liver, stomach, small intestine, and lungs in both groups of mice, and the FBX distributions to the liver and lungs were increased in FBX-PG mice compared to FBX mice. The results suggest the FBX-PG has a suitable pharmacokinetic profile of FBX for improving its oral F value.

The environmental Kuznets curve (EKC) hypothesis posits an inverted U-shaped relationship between economic growth and environmental degradation. However, there is no consensus regarding the EKC hypothesis among countries and regions of different income groups. In this study, we analyze the EKC hypothesis for 158 countries and 44 regions from 1990 to 2020, categorizing them into different income groups based on the World Bank's income classification (low, lower-middle, upper-middle, and high-income countries). Our findings reveal mixed patterns in the EKC across different income levels, highlighting the heterogeneous relationship between economic growth and carbon emissions and showing differentiated patterns among different income levels. While a rise in income for high-income countries should be reflected in a shift toward fewer carbon emissions, for lower-income countries, growth is still associated with rising emissions. This underscores the urgent need for policy interventions that decouple economic development from environmental degradation. A balanced approach to economic growth, which prioritizes carbon neutrality across all stages of development, by tailoring environmental and economic strategies to address CO2 emissions effectively, should be adopted, recognizing the different developmental stages and income levels of countries and regions.

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

Astaxanthin (ATX) is a carotenoid nutraceutical with a poor bioavailability due to its high lipophilicity. We tested a new tailored nano-droplet capable of solubilizing ATX in an oil-in-water micro-environment (LDS-ATX, manufactured by Lyotropic Delivery Systems (LDS)), for its capacity to improve ATX pharmacokinetic profile and anti-oxidant efficacy. We used liquid chromatography tandem mass spectrometry (LC-MS/MS) to compare the pharmacokinetic profile of ATX and LDS-ATX and protein carbonylation and lipid peroxidation assays to compare their basal and lipopolysaccharide (LPS)-induced oxidative damage. Our results show that only LPS-induced oxidative damage was corrected by ATX and LDS-ATX. While in the liver and muscle LDS-ATX was more efficacious than ATX in attenuating oxidative damage to both proteins and lipids, only oxidative damage to lipids was preferably corrected by LDS-ATX in the brain. These results strongly suggest improvement of ATX bioavailability and efficacy by the LDS-ATX nano-formulation.

The aim of the study is to develop a population pharmacokinetic (PopPK) model and to investigate the influence of CYP3A5/CYP3A4 and ABCB1 single nucleotide polymorphisms (SNPs) on the Tacrolimus PK parameters after LCP-Tac formulation in stable adult renal transplant patients. The model was developed using NONMEM v7.5, from full PK profiles from a clinical study (n=30) and trough concentrations (C0) from patient follow-up (n=68). The PK profile of the LCP-Tac formulation was best described by a two-compartment model with linear elimination, parameterised in elimination (CL/F) and distributional (CLD/F) clearances and central compartment (Vc/F) and peripheral compartment (Vp/F) distribution volumes. A time lagged first order absorption process was characterized using transit compartment models. According to the structural part of the base model, the LCP-Tac showed an absorption profile characterized by 2 transit compartments and a mean transit time of 3.02 hours. Inter-individual variability was associated with CL/F, Vc/F and Vp/F. Adding inter-occasion variability (IOV) on CL/F caused a statistically significant reduction in the model minimum objective function MOFV (p<0.001). Genetic polymorphism of CYP3A5 and cluster of CYP3A4/A5 SNPs statistically significantly influenced Tac CL/F. In conclusion a PopPK model was successfully developed for LCP-Tac formulation in stable renal transplant patients. CYP3A4/A5 SNPs as a combined cluster including three different phenotypes (high, intermediate, and poor metabolizers) was the most powerful covariate to describe part of inter-individual variability associated with apparent elimination clearance. Incorporating this covariate in the initial dose calculation and during the therapeutic drug monitoring (TDM) would probably optimize Tac exposure attainments.

Pakistan relies mostly on fossil fuel for fulfilling its energy demand which is expensive as 11 well as not friendly for the environment. The need of the hour is to shift from fossil fuels to renew-12 able energy resources like geothermal, wind, solar etc. to cater for global warming issues. Pakistan 13 has a lot of potential geothermal sites because of several fault lines and hot springs. A sound 14 knowledge of ground temperature is essential to use geothermal energy, which is obtained by drill-15 ing boreholes and putting sensors making it an expensive procedure. Thus, to avoid huge cost for 16 drilling bore holes, particularly for ground temperature analysis, a numerical approach has been 17 considered for determining ground temperature. Furthermore, correlation charts between air and 18 ground temperatures have been developed as there were no proper studies on the ground temper-19 ature of Pakistan. Then, with the help of a boreholes drilled in National University of Sciences and 20 Technology Islamabad Pakistan, the actual ground and numerically calculated temperatures have 21 been compared which shows an error margin in the range between 0.27% for higher depths to 7.3% 22 near surface. Thus, it is shown that the proposed method is easy to implement and better than large 23 scale testing methods for the depths at which geothermal energy is extracted.

Malnutrition in children is a global health problem, particularly in developing countries. The effects of an insufficient supply of nutrients on body composition and physiological functions may have implications for drug disposition and ultimately affect the clinical outcome in this vulnerable population. Physiologically based pharmacokinetic (PBPK) modeling can be used to predict the effect of malnutrition as it links physiological changes to pharmacokinetic (PK) consequences. However, the absence of detailed information on body composition and the limited availability of controlled clinical trials in malnourished children complicates the establishment and evaluation of a generic PBPK model in this population. In this manuscript we describe the creation of physiologically-based bridge to a malnourished pediatric population, by combining information on a) the differences in body composition between healthy and malnourished adults and b) the differences in physiology between healthy adults and children. Model performance was confirmed using clinical reference data. This study presents a physiologically-based translational framework for prediction of drug disposition in malnourished children. The model is readily applicable for dose recommendation strategies to address the urgent medicinal needs of this vulnerable population.

Ceftiofur (CEF) sodium is a third-generation broad-spectrum cephalosporin commonly used in an extra-label manner in dogs for the treatment of respiratory and urinary system infections. To contribute to the literature supporting CEF use in companion animals, we have developed a compartmental, nonlinear mixed-effects (NLME) model of CEF pharmacokinetics in dogs (PK). We then used the mathematical model to predict (via Monte Carlo simulation) the duration of time for which plasma concentrations of CEF and its pharmacologically active metabolites remained above minimum inhibitory concentrations (respiratory tractEscherichia coli spp). Twelve healthy beagle dogs were administered either 2.2 mg/kg ceftiofur-sodium (CEF-Na) intravenously (I.V) or 2.2 mg/kg CEF-Na subcutaneously (S.C). Plasma samples were collected over a period of 72 hours post-administration. To produce a measurement of total CEF, both CEF and CEF metabolites were derivatized into desfuroylceftiofur acetamide (DCA) before analysis by UPLC-MS/MS. No adverse effects were reported after I.V or S.C dosing. The NLME PK models were parameterized using the stochastic approximation expectation maximization algorithm as implemented in Monolix 2018R2. A two-compartment mamillary model with first-order elimination and first-order S.C absorption best described the available kinetic data. Final parameter estimates indicate that CEF has a low systemic clearance (0.25 L/h/kg) associated with a low global extraction ratio E = 0.02) and a moderate volume of distribution (2.97 L/kg) in dogs. The absolute bioavailability after S.C administration was high (93.7%). Gender was determined to be a significant covariate in explaining the variability of S.C absorption. Our simulations predicted that a dose of 2.2 mg/kg CEF-Na S.C would produce median plasma concentrations of CEF of at least 0.5 µg/mL (MIC₅₀) for approximately 30 hours.

Oral drug absorption is the primary route for drug administration. However, this process hinges on multiple factors, including the drug’s physicochemical properties, formulation characteristics, and gastrointestinal physiology. Given its intricacy and the exorbitant costs associated with experimentation, the trial-and-error method proves prohibitively expensive. Theoretical models have emerged as a cost-effective alternative by assimilating data from diverse experiments and theoretical considerations. These models fall into three categories: data-driven models, encompassing classical pharmacokinetics, quantitative-structure models (QSAR), and machine/deep learning. Mechanism-based models include quasi-equilibrium, steady-state, and physiologically based pharmacokinetics, alongside first principles such as molecular dynamics and continuum models. This review provides an overview of recent modeling endeavors across these categories, evaluating their respective advantages and limitations. Additionally, a primer on partial differential equations and their numerical solutions is included in the supplementary materials, recognizing their utility in modeling physiological systems despite their mathematical complexity limiting their widespread application in this field.

Prediction of tumor consistency is valuable for planning transsphenoidal surgery for pituitary adenoma. A prospective study was conducted involving 49 participants with pituitary adenoma to determine whether quantitative pharmacokinetic analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is useful for predicting consistency of adenoma. Pharmacokinetic parameters in the adenomas including volume of extravascular extracellular space (EES) per unit volume of tissue (ve), blood plasma volume per unit volume of tissue (vp), volume transfer constant between blood plasma and EES (Ktrans), and rate constant between EES and blood plasma (kep) were obtained. The pharmacokinetic parameters and the histologic percentage of collagen content (PCC) were compared between soft and hard adenomas using Mann–Whitney U test. Pearson’s correla-tion coefficient was used to correlate pharmacokinetic parameters with PCC. Hard adenomas showed significantly higher PCC (44.08 ± 15.14% vs. 6.62 ± 3.47%, p < 0.01), ve (0.332 ± 0.124% vs. 0.221 ± 0.104%, p = 0.02), and Ktrans (0.775 ± 0.401/min vs. 0.601 ± 0.612/min, p = 0.02) than soft adenomas. Moreover, a significant positive correlation was found between ve and PCC (r = 0.601, p < 0.01). The ve derived using DCE-MRI may have predictive value for consistency of pituitary adenoma.

Camptothecin (CPT) is a potent anticancer drug, and its putative oral administration is envisioned although difficult due to physiological barriers that must be overcome. A comprehensive biophysical analysis of CPT interaction with biointerface models can be used to predict some pharmacokinetic issues after oral administration of this or other drugs. To that end, different models were used to mimic the phospholipid composition of normal, cancer, and blood-brain barrier endothelial cell membranes. The logD values obtained indicate that the drug is well distributed across membranes. CPT-membrane interaction studies also confirm the drug’s location at the membrane cooperative and interfacial regions. The drug can also permeate membranes at more ordered phases by altering phospholipid packing. The similar logD values obtained in membrane models mimicking cancer or normal cells imply that CPT has limited selectivity to its target. Furthermore, CPT binds strongly to serum albumin, leaving only 8.05% of free drug available to be distributed to the tissues. The strong interaction with plasma proteins, allied to the large distribution (VDSS=5.75 ± 0.932 L·Kg-1) and tendency to bioaccumulate in off-target tissues, were predicted to be pharmacokinetic issues of CPT, implying the need to develop drug delivery systems to improve its biodistribution.

A statistical simulation is presented which reproduces the correlation obtained from EPR coincidence experiments without non-local connectivity. Defining spin under the quaternion group reveals hyper-helicity, a hitherto missed attribute of spin. Including this in the treatment, reveals two complementary properties: spin polarization and spin coherence. The former has a CHSH value of 2, and spin coherence has a CHSH = 1 giving CHSH = 3 for an EPR pair. The simulation here gives 2.995. We suggest that Nature has CHSH=3 being considerable more than predicted from quantum mechanics of $2\sqrt{2}$. There are no Local Hidden Variables. We suggest that quaternion spin is more fundamental than Dirac spin. A computer program which performs the simulation without non-local connectivity is described.

Abnormalities in sperm nuclei and chromatin can interfere with normal fertilization, embryonic development, implantation, and pregnancy. We aimed in this study to determine the impact of H2BFWT gene variants in sperm DNA on ICSI outcomes in couples undergoing ART treatment. One hundred and nineteen partners were divided into pregnant (G1) and non-pregnant (G2) groups. After semen analysis, complete DNA was extracted from purified sperm samples. The sequence of the H2BFWT gene was amplified by PCR and then subjected to Sanger sequencing. The results showed that there are three mutations in this gene: rs7885967, rs553509 and rs578953. rs553509 and rs578953 showed significant differences in the distribution of alternative and reference alleles between G1 and G2 (P = 0.0004 and P = 0.0020, respectively). However, there was no association between these SNPs and the studied parameters. This study is the first to shed light on the connection between H2BFWT gene variants in sperm DNA and pregnancy after ICSI therapy. This is a pilot study, so further investigations about these gene variants at the transcriptional and translational levels, in a larger cohort of patients, are needed to determine its functional consequences and to understand the mechanism of how the pregnancy is affected by sperm DNA.

Asphaltene precipitation and deposition pose significant operational challenges in both reservoirs and surface facilities by inducing formation damage. To understand the kinetics involved in asphaltene particle nucleation, growth, and aggregation, this study employed confocal microscopy and centrifuge-based methods under a unified set of experimental parameters. The acquired time-resolved particle size images were analyzed using MIPAR image processing software, while asphaltene mass yield was quantitatively evaluated through centrifugation. Experimental conditions were varied to study the effects of heptane concentration, asphaltene concentration, and shear rate. Notably, this investigation introduces, for the first time, the parameter of particle count as an additional variable influencing asphaltene mass production. This study aims to discern how particle count correlates with asphaltene mass yield over time. Results indicate that the minimum mean particle diameter was observed to be 2 microns, which progressively grew up to 80 microns. The mean particle diameter exhibited a positive correlation with both asphaltene concentration and shear rate, whereas an inverse correlation was seen with heptane concentration. Furthermore, the asphaltene mass yield was found to increase with greater asphaltene and heptane concentrations, as well as with higher shear rates. The relationship between mean particle diameter and mass yield was found to be nonlinear. In the early stages, a higher prevalence of small particles contributed to a greater total particle count, while at later stages, particle aggregation led to the formation of larger particles that influenced the overall asphaltene mass. The insights gained from understanding the relationship between particle diameter, count, and mass yield are crucial for advancing the fundamental science of asphaltene precipitation and deposition. These findings may also guide future research that relies solely on particle counts for assessing asphaltene deposition.

Understanding the physical properties of ultramafic rocks is important for evaluating awide variety of petrologic models of the oceanic lithosphere, particularly upper mantle and lower crust. Hydration of oceanic peridotites results in increasing serpentine content, which affects lithospheric physical properties and the global bio/geochemical cycles of various elements. In understanding tectonic, magmatic and metamorphic history of the oceanic crust, interpreting seismic velocities, rock composition and elastic moduli are of fundamental importance. In this study we show that as serpentine content increases, density decreases linearly with a slope of 7.85. We also correlate increase in serpentine content with a linear decline in shear, bulk and Young’s moduli with slopes of 0.48, 0.77, 0.45 respectively. Our results show that increase in serpentine content of lower crust and forearc mantle could decrease elasticity of lithospehere and result in break-offs. Therefore tectonic processes at peridotite rich slow spreading ridges may be strongly affected by serpentine content, particularly serpentinization may be responsible for discontinuities in thin crust, and formation of weak fault zones.

Hepatic carboxylesterase 1(CES1) metabolizes many prodrugs into active ingredients or direct-acting drugs into inactive metabolites. We aim to develop a semi-physiologically based pharmacokinetic model(Semi-PBPK model) to simultaneously predict pharmacokinetics of CES1 substrates and their active metabolites in liver cirrhosis(LC) patients. Six prodrugs(enalapril, benazepril, cilazapril, temocapril, perindopril and oseltamivir) and three direct-acting drugs (flumazenil, pethidine and remimazolam) were selected. The parameters including organ blood flows, plasma binding protein concentrations, functional liver volume, hepatic enzymatic activity, glomerular filtration rate(GFR) and gastrointestinal transit rate were introduced into the simulation. Pharmacokinetic profiles of these drugs and their active metabolites were simulated in 100 virtual subjects. The developed semi-PBPK model, following validation in healthy subjects, was extrapolated to LC patients. Most of the observations are within the 5% and 95% quantile of simulations from 100 virtual patients. The estimated AUC and Cmax are within 0.5-2-fold of observation. The sensitivity analysis showed that the decreased plasma exposure of active metabolite due to the decreased CES1 was partly attenuated by the decreased GFR. Conclusion: The developed PBPK model has successfully predicted pharmacokinetics of CES1 substrates and their metabolites in healthy subjects and LC patients, which assists in tailoring dosages of CES1 substrates in LC patients.

Physiologically Based Pharmacokinetic Models (PBPK) are mechanistical tools generally employed in the pharmaceutical industry and environmental health risk assessment. These models are recognised by regulatory authorities for predicting organ concentration-time profile, pharmacokinetic and daily intake dose of xenobiotics. Extension of PBPK models to capture sensitive populations like pediatric, geriatric, pregnant females, fetus etc. and diseased population like renal impairment, liver cirrhosis etc. is a must. However, the current modelling practice and existing models are not mature enough to confidently predict the risk in these populations. A multidisciplinary collaboration between clinicians, experimental and modeler scientist is vital to improve the physiology, and calculation of biochemical parameters for integrating the knowledge and refining existing PBPK models. Specific PBPK covering compartments like cerebrospinal fluid, and hippocampus are required to gain mechanistic understanding about xenobiotic disposition in these sub-parts. The PBPK model assists in building quantitative adverse outcome pathways (qAOPs) for several endpoints like developmental neurotoxicity (DNT), hepatotoxicity and cardiotoxicity. Machine learning algorithms can predict physicochemical parameters required to develop in-silico models where experimental data is unavailable. Integrating machine learning with PBPK carries the potential to revolutionize the field of drug discovery and development and environmental risk. Overall, this review tried to summarize the recent developments in the in-silico models, building qAOPs, use of machine learning for improving existing models along with a regulatory perspective. This review can act as a guide for toxicologists who wish to build their careers in kinetic modeling.

The physical properties of nano-fertilizers (NFs) are important in determining their performance, efficacy, and environmental interactions. Nano-fertilizers, due to their small size and high surface area-to-volume ratio, enhance plant metabolic reactions, resulting in higher crop yields. The properties of nano-fertilizers depend on the synthesis methods used. The nanoparticle's nutrient use efficiency (NUE) varies among plant species. This review aims to analyze the relationship between the physical properties of NF and their influence on crop performance and nutrient uptake efficiency. The review focuses on the physical properties of NFs, specifically their size, shape, crystalline, and agglomeration. This review found that smaller particle-sized nanoparticles exhibit higher nutrient use efficiency than larger particles. Nano-fertilizer-coated additives gradually release nutrients, reducing the need for frequent application and addressing limitations associated with chemical fertilizer utilization. The shapes of nano-fertilizers have varying effects on the overall performance of plants. The crystalline structure of nanoparticles promotes a slow release of nutrients. Amorphous nano-fertilizers improve the NUE and, ultimately, crop yield. Agglomeration results in nanoparticles losing their nanoscale size, accumulating on the outer surface, and becoming unavailable to plants. Understanding the physical properties of nano-fertilizers is crucial for optimizing their performance in agricultural applications.

This short paper reveals a simple methodology to create local-correlation models suitable for the closed-form pricing of multi-asset financial derivatives. The multivariate models are built to ensure two conditions, first, marginals follow desirable processes, e.g. we choose the Geometric Brownian Motion (GBM), popular for stock prices. Second, the payoff of the derivative should follow a desired one dimensional process. These conditions lead to a specific choice of the dependence structure, in the form of a local-correlation model. Two popular multi-asset options are entertained, a spread option and a basket option.

Recently, with the rapid advancement of technology, Internet of Things (IoT‏‏‏‏) security has become more efficient and more complex, especially for resource-limited devices such as embedded devices, wireless sensors and radio frequency identification tags (RFID). Lightweight block ciphers (LBCs) provide security for these technologies to protect them against adversaries, but the need for low power consumption in LBCs is one of the most important challenges for IoT‏ technologies. Furthermore, these LBCs are subject to multiple attacks and side channel attacks (SCAs) are among the mentioned threats to these cryptosystems. A type of SCA is correlation power analysis (CPA) in which the attacker tries to reach the key using the relationship between the power consumption of the chip during the algorithm running, data processing, and operations. In this article, a CPA attack is designed to discover master key of the Midori-64 block cipher. According to the proposed method, an attack is done to the first round S-boxes to get half of the key bits. Then, the second round S-boxes were attacked to other half of key bits just use 300 plain text samples. Finally, the most important physical attacks performed on the Midori, are compared to our proposed CPA attack.

In social sciences, a plethora of studies utilize nominal data to establish the relationship between the variables. This, in turn, requires the correct use of correlation technique. The choice of correlation technique depends upon the underlying assumptions and power of the test of significance. The objective of the research is to explore the best measure of association for nominal data in terms of size, power and bias in estimation. Monte Carlo simulations reveal that the Phi and Pearson correlation statistics performs equally well in terms of size, power, and bias for naturally dichotomous variables. When both variables are artificially dichotomized, the Tetrachoric statistic has an edge in terms of bias to Pearson correlation statistic. If one variable is continuous and other is artificially dichotomized, the Biserial correlation measure turns out to be less biased as compared to Pearson statistic although both statistics exhibit similar power and size properties. If one variable is continuous and other is naturally dichotomized, it is hard to choose between the Point Biserial and Pearson correlation measures. Finally, if one variable is naturally dichotomous and other is artificially dichotomized, correlation coefficient V is compared with Pearson, Phi and Tetrachoric correlation techniques in terms of bias in estimate. The results indicate that the Tetrachoric statistic considerably overestimates the correlation value against non-normal distributions. Pearson and Phi correlation slightly underestimate the correlation value. In contrast, the correlation statistic V perform well.

A newly UHPLC-MS/MS method development and validation for S-Allyl Cysteine was used to evaluate the comparative pharmacokinetic parameters. SC PLGA NPs were developed by the emulsion solvent evaporation method. SC PLGA NPs showed their drug loading and encapsulation efficiency i.e. 5.13±0.10% and 82.36±4.01%, respectively. SC PLGA NPs showed a spherical morphology on an average size (134.8±4.61nm), PDI: 0.277±0.004, and −25.3±1.03mV zeta-potential is suitable for oral delivery. Development and validation of the UHPLC-MS/MS bioanalytical method were performed successfully for PK-parameters examinations with 1.219-minutes RT, MS (162.00/73.10), and a total run-time was 2.0-minutes. 1.0–1000.0ng/mL was a linear-range with inter & intra-day accuracy (92.55–99.40%) followed by precision (1.88–4.23%). SC PLGA NPs oral bioavailability was significantly higher (**p<0.01) as compared to SC-S treated groups (iv & oral). We found that the antimicrobial activity of SC PLGA NPs was more effective than pure S-Allyl-L-Cysteine with significant results (p<0.01) as compared to SC-S. SC PLGA NPs showed fitted physicochemical and enhanced antimicrobial properties which can be helpful for oral administration. On the basis of our observations, SC PLGA NPs suggested the highest potential for the improvement of oral bioavailability with a sustained and controlled release of S-Allyl-L-Cysteine delivery.

We describe the development and validation of a HPLC-MS/MS method to assess the pharmacokinetics and tumour distribution of fenretinide, a synthetic retinoid chemically related to all-trans-retinoic acid, after administration of a novel oral nanoformulation of fenretinide, called bionanofenretinide (BNF). BNF was developed to overcome the major limitation of fenretinide: its poor aqueous solubility and bioavailability due to its hydrophobic nature. The method proved to be reproducible, precise, and highly accurate for the measurement of the drug and the mains metabolites. The lower limit of quantification resulted 1 ng/mL. The curve range of 1-500 ng/mL and 50-2000 ng/mL, for plasma and tumor homogenate respectively, was appropriate for the analysis, as demonstrated by the accuracy between 96.8% and 102.4% for plasma and 96.6-102.3% for tumor. The inter-days precision and accuracy determined on quality controls at 3 different levels were in ranges of 6.9%-7.5% and 99.3-101.0% and 0.96-1.91% and 102.3-105.8% for plasma and tumour, respectively.

Tinnitus is a symptom often associated with hearing loss (HL) and is in many cases more burdening to the individual than the HL itself. Many approaches have been made to explain the development and chronification of the phantom percept as well as different treatment strategies to lower the tinnitus related burden. In many studies, the variance of the HL data is high and therefore the interpretation of specific data might be difficult. With this retrospective study, we attempt to explain a part of this variance by investigating specifically the effects of non-auditory comorbidity categories on pure-tone audiometric data in a tinnitus patient collective that was homogeneous with respect to auditory comorbidities. We found age dependent as well as number of non-auditory comorbidity (e.g. diabetes mellitus) dependent differences in the mean HL of the tinnitus patients as well as differences in the peak HL frequency relative to the tinnitus frequency. The analysis of the age dependent HL within the different non-auditory comorbidities revealed specific – partially opposed – effects of endocrine, circulatory, muscle-skeletal and digestive disease categories on the hearing thresholds of tinnitus patients. Taken together we argue that in future tinnitus (and non-tinnitus) patient studies also non-auditory comorbidities should be taken into account as possible covariables that might explain the variance found in the auditory threshold development of these patients.

Synaptic transmission is essential for nervous system function and the loss of synapses is a known major contributor to dementia. Alzheimer’s disease dementia (ADD) is characterized by synaptic loss in the mesial temporal lobe and cerebral neocortex, brain areas associated with memory and cognition. The association of synaptic loss and ADD was established in the late 1980s and it has been estimated that 30-50% of neocortical synaptic protein is lost in ADD, but there has not yet been a quantitative profiling of different synaptic proteins in different brain regions in ADD from the same individuals. Very recently, PET imaging of synapses is being developed, accelerating the focus on the role of synaptic loss in ADD and other conditions. In this study, we quantified densities of two synaptic proteins, the presynaptic protein SNAP25 and the postsynaptic protein PSD95 in human brain using enzyme-linked immunosorbent assays (ELISA). Protein was extracted from the cingulate, hippocampus, frontal, visual, and entorhinal cortex from cognitively unimpaired controls, subjects with mild cognitive impairment (MCI) and demented subjects with different levels of Alzheimer’s pathology. SNAP25 is significantly reduced in ADD when compared to controls in frontal cortex, visual cortex and cingulate; while hippocampus showed a smaller, non-significant reduction and entorhinal cortex concentrations were not different. In contrast, all brain areas showed lower PSD95 concentrations in ADD when compared to non-demented controls, although in hippocampus this failed to reach significance. Interestingly, cognitively unimpaired cases with high levels of AD pathology had higher levels of both synaptic proteins in all brain regions. SNAP25 and PSD95 concentrations significantly correlated with densities of neurofibrillary tangles, amyloid plaques and Mini Mental State Examination scores. Our results suggest that synaptic transmission is affected by ADD in multiple brain regions. Differences were less marked in entorhinal cortex and hippocampus, most likely due to a ceiling effect imposed by the very early development of neurofibrillary tangles in older people in these brain regions.

Due to the content of biologically active substances, sea buckthorn (Hippophae rhamnoides L.) is of growing interest to scientists, the food industry, pharmaceuticals, cosmetology and consumers. The aim of this study is to investigate the correlation between the chemical composition (Carotenoid content (CC), Ascorbic acid content (AAC), Total dry matters (TDM), Titratable acidity (TA), pH, Organic acids (OA)) and the Antibacterial effect (AA) (Diameter of the inhibition zone in mm of Bacillus pumilus) of four species of sea buckthorn (Clara, Dora, Cora, Mara), cultivated in the Republic of Moldova. The sea buckthorn species tested was found to have a different Carotenoid content (1.79±0.43 … 48.92±0.61 mg/100g), Ascorbic acid content (74.36±0.60 … 373.38±2.29 mg/100g), Organic acids (malic acid 5.8±0.02 ... 13.4±0.01 mg/100g, citric acid 0.08±0.00 ... 0.32±0.01 mg/100g, succinic acid 0.03±0.00 ... 1.1±0.00 mg/100g), Total dry matters (16.71±0.05 … 24.54±0.09 %), Total acidity (2.15±0.05 ... 8.76±0.00 %), and pH value (2.73±0.02 ... 3.00±0.07). The microbial activity of sea buckthorn, evaluated by the diameter of the inhibition zone, constituted for Bacillus pumilus (3.70…15.91mm/g-1 for whole sea buckthorn fruits and respectively 13.33…26.67 mm/g-1 for sea buckthorn puree).

Although impending urbanization is a well-acknowledged problem, there is a rising concern about how the urban forms will change and what can be the impacts on the global energy demand. As hubs of economic, social and cultural activities, cities are major energy consumers and GHG emissions. Energy consumption is a technical or a spatial problem? From Newman and Kenworthy to today, several studies have tried to shed light on this nexus. In this work, the controversial paradigm of urban density is discussed as a key component of the fight against climate change impacts. Concerning energy consumption, an in-depth bibliometric analysis is developed to identify the interdependencies of the terms. As a key ‘promise’ of an efficient urban configuration, density has been the core of diverse studies but with still under exploration arguments. This work provides a way forward for planners seeking to design strategies related to dense urban tissues exploring controversial paradigms as a key solution for energy-efficient problems.

Purpose: To determine whether 24-hour IOP monitoring can be a predictor for glaucoma progression and to analyze the inter-eye relationship of IOP, perfusion and progression parameters. Methods: We extracted data from manually drawn IOP curves with HIOP-Reader, a software suite we developed. The relationship between measured IOPs and mean ocular perfusion pressures (MOPP) to retinal nerve fiber layer (RNFL) thickness was analyzed. We determined the ROC curves for peak IOP (Tmax), average IOP (Tavg), IOP variation (IOPvar) and historical IOP cut-off levels to detect glaucoma progression (rate of RNFL loss). Bivariate analysis was conducted to check for various inter-eye relationships. Results: 217 eyes were included. The average IOP was 14.8±3.5 mmHg, with a 24-hour variation of 5.2±2.9 mmHg. 52% of eyes with RNFL data showed disease progression. There was no significant difference in Tmax, Tavg and IOPvar between progressors and non-progressors (all p>0.05). Except for Tavg and the temporal RNFL, there was no correlation between disease progression in any quadrant, Tmax, Tavg and IOPvar. 24-hour and outpatient IOP variables had poor sensitivities and specificities in detecting disease progression. The correlation of inter-eye parameters was moderate; correlation with disease progression was weak. Conclusion: In line with our previous study, IOP data obtained during a single visit (outpatient or inpatient monitoring) make for a poor diagnostic tool, no matter the method deployed. Glaucoma progression and perfusion pressure in left and right eyes correlated weakly to moderately with each other.

The magnetic field of the earth plays an important role in the ecosystem, and the magnetic field of celestial bodies is also important in the formation of cosmic large-scale structures, but the origin and evolution of the celestial magnetic field is still an unresolved mystery. Many hypotheses to explain the origin have been proposed, but there are some insurmountable difficulties for each one. At present, the theory widely accepted in scientific society is the dynamo model, it says that, the movement of magnetofluid inside celestial bodies, which can overcome the Ohmic dissipative effect and generate persistent weak electric current and macroscopic magnetic field. However, this model needs an initial seed magnetic field, and the true values of many physical parameters inside the celestial body are difficult to obtain, and there is no stable solution to the large range of fluid motion. These are all difficulties for the dynamo model. Furthermore, it is difficult for the dynamo to explain the correlation between the dipole magnetic field and angular momentum of a celestial body. In this paper, by calculating the interaction between spin of particles and gravity of celestial body according to Clifford algebra, we find that a rotational celestial body provides a field $\Omega^\alpha$ for spins, which is similar to the magnetic field of a dipole, and the spins of charged particles within the celestial body are arranged along the flux line of $\Omega^\alpha$, then a macroscopic magnetic field is induced. The calculation shows that the strength of $\Omega^\alpha$ is proportional to the angular momentum of the celestial body, which explains the correlation between the magnetic intensity and angular momentum. The results of this paper suggest that further study of the effects of internal variables such as density, velocity, pressure and temperature of a celestial body on $\Omega^\alpha$ may provide some new insights into the origin and evolution of celestial magnetic field.

In the past two decades the world experienced an exceptional number of unprecedented extreme weather events, some causing major human suffering and economic damage, such as the March 2012 heat event, which was called “Meteorological March Madness.” From the beginning of space era a correlation of solar flares with pressure changes in atmosphere within 2–3 days or even less was reported. In this study we wanted to test the possible relation of highly warm weather events in North-East America with Solar Energetic Particle (SEP) events. For this reason we compared ground temperatures T_M in Madison, Wisconsin, with energetic particle fluxes P measured by the EPAM instrument onboard the ACE spacecraft. In particular, we elaborated case events and the results of a statistical study of the SEP events related with the largest (Dst ≤ −150nT) Coronal Mass Ejection (CME)-induced geomagnetic storms, between with the years 1997–2015. The most striking result of our statistical analysis is a very significant positive correlation between the highest temperature increase_. ΔT_M and the time duration of the temperature increase ΔT_M (r = 0.8, p <0.001) at “winter times” ( r = 0.5, p , 0.01 for the whole sample of 26 SEP examined events). The time response of T_M to P was found to be in general short (a few days), but in the case of March 2015, during a gradual P8 increase, a cross-correlation test indicated highest c.c. within 1 day (p < 0.05). The March 2012 “meteorological anomaly” was elaborated in the case of South-East Europe, where, beside a period of strong winds and rainfall (6-13.3.2012), intense precipitation in North-East Greece (Alexandroupoli) were found to be correlated with distinct high energy flux enhancements. A rough theoretical interpretation is discussed for the space—atmospheric extreme weather relationship we found. However, much work should be done to achieve early warning of space weather dependent extreme meteorological events. Such future advances in understanding the relationships between space weather and extreme atmospheric events would improve atmospheric models and help people’s safety, health and life.

The crucial stages in the geochemical evolution of the Earth’s crust, ocean, and atmosphere could be explained by the assumed low-energy nuclear reactions (LENR) that are triggered by seismic activity. LENR result in the fission of medium-weight elements accompanied by neutron emissions, involving Fe and Ni as starting elements, and C, N, O as resultants. Geochemical data and experimental evidences support the LENR hypothesis. A spectral analysis of the period 1955-2013 shows common cycles between interannual changes in atmospheric CO2 growth rate and global seismic-moment release, whereas the trending behavior of the atmospheric CO2 was in response to the anthropogenic emissions. Assuming a correlation between such seismic and atmospheric fluctuations, the latter could be explained by cycles of worldwide seismicity, which would trigger massively LENR in the Earth’s Crust. In this framework, LENR from active faults could be considered as a relevant cause of carbon formation and degassing of freshly-formed CO2 during seismic activity. However, further studies are necessary to validate the present hypothesis which, at the present time, mainly aims to stimulate debate on the models which regulates atmospheric CO2.

The purpose of the study was to describe and compare the pharmacokinetics of five commercial edible marijuana products, determine the influence of body composition on pharmacokinetics, and, in light of epidemiology suggesting marijuana may offer diabetes protection, explore the influence of edible marijuana on glucose tolerance. Seven regular users of marijuana self-administered five edible products in a randomized crossover design; each product contained 10mg of delta-9-tetrahydrocannabinol (THC). 30-minutes following marijuana ingestion, participants imbibed a 75g glucose beverage. Time-to-peak plasma THC concentration ranged between 35 and 90 minutes; maximal plasma THC concentration (Cmax) ranged between 3.2 and 5.5 ng/mL. Differences between products in plasma THC concentration during the first 20-to-30 minutes were detected (P=0.019). Relations were identified between body composition and pharmacokinetic parameters for some products; however, none of these body composition characteristics were consistently related to pharmacokinetics across all five of the products. Edible marijuana had no effect on oral glucose tolerance compared with a marijuana-free control (Matsuda Index; P>0.395). Commercially available edible marijuana products evoke different plasma THC concentrations shortly after ingestion, but do not appear to influence acute glucose regulation. These data may allow marijuana users to make informed decisions pertaining to rates of edible marijuana ingestion and avoid overdose.

Because of lower solubility and considerable metabolism, vardenafil (VRD) bioavailability is 15 %. To get over this obstacle, this study aimed to increase the solubility, hasten the onset of action, and mask the unpleasant taste of VRD utilizing β-cyclodextrin (β-CD) and formulation of the inclusion complex as oral disintegrating tablets (ODTs). The solubility of the obtained complexes in various ratios has been studied. A Box-Behnken design (BBD) was utilized to investigate the influence of excipients on the quality of ODTs. The solubility of VRD was improved at 1:2 drug: β-CD ratio. The formulated VRD-ODTs exhibited satisfying results regarding the hardness and disintegration time. In addition, in vivo taste masking and disintegration time showed improved results, after placing the tablets in the oral cavity of the healthy volunteers. The pharmacokinetic parameters for the optimized VRD–ODTs exhibited a significant improvement with P < 0.05 in the maximum plasma concentration and reduction in the time needed to reach this concentration when compared with the marketed tablets. Finally, the optimized VRD-ODTs exhibited increased oral absorption of VRD and subsequent decreasing the time of onset of clinical effect and masking the unpleasant taste, which is favored for patients with erectile dysfunction.

All sensing systems have some inherent error. Often, these errors are systematic, and observations taken within a similar region of space and time can have correlated error structure. However, the data from these systems are frequently assumed to have completely independent and uncorrelated error. This work introduces a correlated error model for GNSS-reflectometry (GNSS-R) using observations from NASA’s Cyclone Global Navigation Satellite System (CYGNSS). We validate our model against near-simultaneous observations between two CYGNSS satellites, and double difference our results with modeled observables to extract the correlated error structure due to the observing system itself. Our results are useful to catalogue for future GNSS-R missions and can be applied to construct an error covariance matrix for weather data assimilation.

Recently, more and more countries are entering the global race for university competitiveness. On the one hand, global rankings are a convenient tool for quantitative analysis. On the other hand, their indicators are often difficult to quickly calculate, they often contradict each other. We thought about using widely available indicators for a quick analysis of the University's publication strategy. We opted for the normalized citation indicators available in SciVal analytical tool, i.e. Source Normalized Impact per Paper (SNIP) and Field-Weighted Citation Impact (FWCI). We have demonstrated the possibility of applying the correlation analysis to the impact indicators of a document and a journal on the sample of the social and humanitarian fields at Peoples' Friendship University of Russia. Particular attention was paid to the application of the results in practice.

We propose a novel credit risk measurement model for Corporate Default Swap spreads, that combines vector autoregressive regression with correlation networks. We focus on the sovereign CDS spreads of a collection of countries, that can be regarded as idiosyncratic measures of credit risk. We model them by means of a vector autoregressive regression model, composed by a time dependent country specific component, and by a contemporaneous component that describes contagion effects among countries. To disentangle the two components, we employ correlation networks, derived from the correlation matrix between the reduced form residuals. The proposed model is applied to ten countries that are representative of the recent financial crisis: top borrowing/lending countries, and peripheral European countries. The empirical findings show that the proposed model is a good predictor of CDS spreads movements, and that the contemporaneous component decreases prediction errors with respect to a simpler autoregressive model. From an applied viewpoint, core countries appear to import risk, as contagion increases their CDS spread, whereas peripheral countries appear as exporters of risk. Greece is an unfortunate exception, as its spreads seem to increase for both idiosyncratic factors and contagion effects.

Outbreaks of Ebola ebolavirus (EBOV) have been associated with high morbidity and mortality. Milestones have been reached recently in the management of EBOV disease (EVD) with licensure of an EBOV vaccine and two monoclonal antibody therapies. However, neither vaccines nor therapies are available for other disease-causing filoviruses. In preparation for such outbreaks, and for more facile and cost-effective management of EVD, we seek a cocktail containing orally available and room temperature stable drugs with strong activity against multiple filoviruses. We previously showed that (bepridil + sertraline) and (sertraline + toremifene) synergistically suppress EBOV in cell cultures. Here we describe steps towards testing these combinations in a mouse model of EVD. We identified a vehicle suitable for oral delivery of the component drugs and determined that, thus formulated the drugs are equally active against EBOV as preparations in DMSO, and they maintain activity upon storage in solution for up to seven days. Pharmacokinetic (PK) studies indicated that the drugs in the oral delivery vehicle are well tolerated in mice at the highest doses tested. Collectively the data support advancement of these combinations to tests for synergy in a mouse model of EVD. Moreover, mathematical modeling based on human oral PK projects that the combinations would be more active in humans than their component single drugs.

Multiple Sclerosis (MS) is a chronic autoimmune disorder characterized by the demyelination of neural fibers in the central nervous system. Understanding the impact of demyelination on neural network efficiency is crucial for elucidating the pathophysiological mechanisms underlying MS. This study aims to model the effects of demyelination on neural network efficiency, specifically focusing on how increased resistance and path lengths due to demyelination correlate with the clinical symptoms of MS. We employed a graph-theoretical approach to simulate neural networks, introducing varying degrees of demyelination. The demyelination was represented by increasing the resistance (weights) of selected edges within the network, affecting both random and clustered distributions of network connections. The primary metric analyzed was the average shortest path length, indicative of network efficiency. The models demonstrated a significant increase in the average shortest path length in demyelinated networks compared to intact ones. Specifically, networks with clustered demyelination exhibited localized inefficiencies, correlating with the focal nature of MS lesions. The increase in path length was associated with reduced signal transmission efficiency, providing insights into a range of MS symptoms including motor and sensory impairments, cognitive dysfunction, visual disturbances, and fatigue. The graph-theoretical model of neural network demyelination offers a novel perspective on how structural changes in the brain's connectivity due to MS can lead to diverse clinical manifestations. While the model simplifies the complexity of neural networks, it underscores the potential of computational approaches in understanding and predicting the course of neurological disorders like MS.

Cenobamate is approved by the European Medicine Agency for the treatment of adult patients with epilepsy (PWEs) who suffer from ongoing focal-onset seizures despite appropriate treatment with at least two established antiseizure medications. Pivotal trials and post-marketing real-world observational studies have suggested a high efficacy with unusually high seizure-free rates. We sought to investigate the serum trough levels of cenobamate under steady-state conditions in seizure-free versus non-responding PWEs, and in PWEs who experienced adverse events versus those who did not. We analyzed samples from 101 PWEs treated with adjunct cenobamate under steady-state conditions. In all, 36 PWEs were seizure-free and 65 were non-responders. In 31 PWEs, adverse events were apparent, whereas in the remaining 70, no tolerability issues were reported. We found a linear correlation between the daily doses (range: 100 mg – 400 mg) and the plasma levels (3.8 mg/l – 54.6 mg/l). Neither the daily doses nor the plasma levels differed significantly between seizure-free and non-responding PWEs or between PWEs with a satisfactory tolerability and those who experienced adverse events. The main reason for this result was that the individual therapeutic ranges varied widely: seizure freedom and adverse effects were observed alongside low doses and plasma levels in some PWEs. Conversely, there were examples of PWEs who did not respond or who reported no tolerability issues at high doses or plasma levels. Still, to evaluate the individual therapeutic range and to better understand the influence of other drugs in cases where concomitant medications are used, the therapeutic drug monitoring of cenobamate may be useful.

Increasing groundwater levels (GWL) may become one of the most serious issues for Odessa City, Ukraine. This study investigated the spatial distribution characteristics and multifractal scaling behaviour of groundwater level/depth fluctuation for a Quaternary aquifer in Odessa City using a geostatistical approach and a Multifractal Detrended Fluctuation Analysis (MF-DFA). These two methods were applied to monthly GWL fluctuation time series from 1970 to 2020 to monitor 72 hydrogeological wells situated in different parts of Odessa City. The spatial distribution of GWL revealed an overall trend of decline and recovery from 1970 to 2020 in the study area, except for most of the southern region, where a persistent recovery of groundwater depth was observed. The MF-DFA results suggest that the dynamics of GWL fluctuations have multifractal characteristics in the Odessa City area. In addition, both long-range correlation and fat-tail probability distribution contribute to multifractality. However, long-range correlations among fluctuations made a major contribution to the observed multifractality of the GWL fluctuations time series. The generalized Hurst exponent shows a wide range of change (0.20 &lt; h(q) &lt; 2.85), indicating the sensitivity of GWL fluctuations to changes in small scale factors and large-scale factors. Regarding the long range correlations of GWL depth, the Hurst exponents (q = 2) demonstrated the positive persistence of groundwater depth recovery in the southern region and the persistence of groundwater depth variation in the other regions of the study area. The dynamic changes in GWL depth in the Odessa City area may be affected by both natural structural and anthropogenic factors.

Adolescents’ eating disorders and disordered eating behaviours appear to be a growing public health concern. The aetiology of these conditions is complex, as many different factors interact for their development. Among them, family factors such as parenting styles and comments regarding weight from family members are considered critical and are extensively researched. However, the impact of parental dieting has received less attention. A literature review was conducted in order to examine the relationship between parental engagement in weight-reduction dieting and their adolescent offspring’s disordered eating behaviours. The review was conducted in three databases (PubMed, Scopus and Google Scholar). A number of studies indicated that adolescents whose parents were engaged in dieting in order to lose weight are more likely to showcase disordered eating behaviours. However, research about this relationship is very scarce. More studies on the link between parental eating and dieting habits and the risk of disordered eating in adolescents are needed. Moreover, parents should be informed regarding the possible risks when they choose to follow weight-loss diets and the importance of adopting healthy eating and weight-control habits for the whole family.

Understanding of the correlation between the magnetomechancial coupling factors (k) and damping factors (Q^-1) is a key pathway to enhance the magnetomechanical power conversion ef-ficiency in laminated magnetoelectric (ME) composites by engineeringly manipulating the magnetic and mechanical properties of Fe-based amorphous metals. The k and Q^-1 factors of FeSiB amorphous ribbons annealed in air at different temperatures are investigated. It is found that k and Q^-1 factors are affected by both magnetic and elastic properties. The magnetic and elastic properties are equalized in terms of the magnetomechanical power efficiency for the low temperature annealing. The k and Q^-1 of FeSiB-based epoxied laminates with different stacking numbers show that the -3 dB bandwidth and Young’s modulus are equalized in terms of the magnetomechanical power efficiency for the high lamination stacking.

This paper shows the results of applying high-resolution Unmanned Aircraft System (UAS) photogrammetric surveying on a large landslide. A real case study, where permanently installing GCPs could be complex, where natural shaped and formed land pose severe limitations in deploying ground targets with optimal geometric configuration. We analysed performances in terms of survey accuracy obtained by performing photogrammetric surveys through the Zenmuse P1 DJI optical camera and Phantom 4 Pro 2. In combination with DJI Matrice 300 UAS, the P1 camera allows direct georeferencing through GNSS observations in RTK mode. Photogrammetric surveys, performed through different georeferencing methods, have been compared. Several targets have been permanently installed on the ground over the maximum vegetation height to guarantee long-lasting reference over the years in the area, which is characterised by a diffuse short vegetation coverage. Multitemporal UAS surveys have been then compared using Digital Image Correlation (DIC) algorithms, and deformation maps have been produced. Afterwards, DIC results were compared with observations made by the GNSS ground-based permanent receivers resulting in a standard deviation of 0,077 m. Through results analysis, good accordance between ground-based GNSS observations and DIC analysis on the photogrammetric surveys have been identified for the same time span. To conclude, this type of landslide presents a moderate deformation speed; in such a case, effective deformations monitoring could be achieved using pseudo-direct georeferencing, which permitted a 0.24 m accuracy on the whole tested area.

Fresnel incoherent correlation holography (FINCH) is a well-established incoherent imaging technique. In FINCH, three self-interference holograms are recorded with calculated phase differences between the two interfering, differently modulated object waves and projected into a complex hologram. The object is reconstructed without the twin image and bias terms by a numerical Fresnel back propagation of the complex hologram. A modified approach to implement FINCH by a single camera shot by pre-calibrating the system involving recording of the point spread function library and reconstruction by a non-linear cross-correlation has been introduced recently. The expression of the imaging characteristics from the modulation functions in original FINCH and the modified approach by pre-calibration in spatial and polarization multiplexing schemes are reviewed. The study reveals that a reconstructing function completely independent of the function of the phase mask is required for the faithful expression of the characteristics of the modulating function in the image reconstruction. In polarization multiplexing method by cross-correlation, a partial expression was observed, while in spatial multiplexing method by cross-correlation, the imaging characteristics converged towards a uniform behavior.

This work evaluates the surface water quality in terms of physico-chemical parameters of the Brahmani River, Odisha using statistical analysis involving the calculation of correlation coefficient and regression equation. Besides this, the work also highlights and draws attention towards the “Water Quality Index” in a simplified format which may be used at large and could represent the reliable picture of water quality. Surface water quality data is taken from OSPCB of various location i.e. Panposh D/S, Rourkela D/S, Rengali, Talcher U/S, Kamalanga D/S, Bhuban, Pattamundai and was assessed for summer, monsoon, winter for the years 2011, 2012, 2013, 2014 and 2015. Average of values, minimum of values and maximum of values of water quality parameters were obtained seasonally over the above mentioned years. Besides this, the standard deviation for the water quality parameters was also obtained for water quality parameters namely pH, Temperature, DO, TDS, Alkalinity, EC, Na+, Ca2+, Mg2+, K+, F-, Cl-, NO3-, SO42- and PO42-. Seasonal changes in various physical and chemical parameters were analysed.The values obtained were compared with the guideline values for drinking water by Bureau of Indian Standard (BIS). A systematic correlation and regression study is carried out for three seasons, showed linear relationship among different water quality parameters. This provides an easy and rapid method of monitoring water quality. Highly significant (0.8< r <1.0), moderately significant (0.6< r <0.8) and significant (0.5< r <0.6) correlations between the parameters have been worked out. High correlation coefficient has been observed between TDS,EC-Na+, Ca2+, Cl-, SO42- ; Na+- Cl-. From the collected quantities, certain parameters were selected to derive WQI for the variations in water quality of each designated sampling site. WQI of Brahmani River ranged from 36.7 to 44.1 which falls in the range of good quality of water.Panposh D/S and Rourkela D/S showed poor water quality in summer and winter season. It is shown that WQI may be a useful tool for assessing water quality and predicting trend of variation in water quality at differentlocations in the Brahmani River.

Time evolution of the quantum correlation of the hybrid qubit-qutrit system in multilocal and global dephasing under the effect of a classical noises environment is presented. We considered the qutrit in z direction and the qubit x direction. In addition, our system presents two configurations: the different and the common environment and our discussion involves three types of noises: A Static Noise (SN), Random Telegraph Noise (RTN) and Ornstein- Uhlenbeck noise (OU). By using the density matrix approach to determine the evolution of the state of the system, the found that the static noise is fatal for the quantum entanglement, the quantum correlation and for RTN and OU noises the quantum entanglement, the quantum correlation decreases monotonically with a sufficiently long time. Therefore, we can say that, entanglement and the quantum correlation are more robust to the noise precisely those Random telegraph noise and Ornstein-Uhlenbeck noise.

Abstract Background: Temporomandibular disorders (TMD) are a range of clinical problems related to the temporomandibular joint (TMJ), chewing muscles, and surrounding facial structures. Functional magnetic resonance studies suggest that these disorders affect over 5% of the population. The relationship between dental occlusion and TMD has been a topic of debate in dentistry; some researchers suggest using lateral cephalograms and cephalometric data to identify which morphological profiles and types of malocclusion are most likely to cause TMD. The aim of this study is to identify the morphological profiles and associated skeletal malocclusions that have the greatest influence on the development of TMD. This will be accomplished through the analysis of cephalometric data obtained from cephalograms and condylar section images of patients from the Orthognathodontics Department of Chieti, who underwent low-dose cbct during their initial visit. Matherial and methods: This study, conducted at the Orthognathodontics Department of Gabriele D’Annunzio University in Chieti, examined a group of 67 patients (both males and females) presenting with signs of temporomandibular joint disorders (TMD). The inclusion criteria for the study were first-time TMD diagnosis, age 18 and above, and accessible medical records, wide field of view cone beam low dosage, and photographs. Patients with a history of tumor, trauma, surgical interventions in the jaw and facial area, fractures, and other craniofacial anomalies were excluded from the study. The aim of the study is to further understand the morphological profiles and associated skeletal malocclusions that contribute to TMD. Results: male patients: sagittal profile: 56% exhibited a skeletal Class II profile due to mandibular retrognathia. Vertical Profile: 73% were brachyfacial with a hypodivergent pattern. Dental Relationships: Increased overjet and a tendency towards deep bite were observed. 23% exhibited deep bite, 20% were normodivergent, and 8% were dolichofacial. The soft tissue profile tended towards flatness. Condyle Position: in Class II hypodivergent males, the condyle was non-concentric and positioned more posteriorly. In mesiodivergent males, the condyle was concentric, while in hyperdivergent males, it was slightly anterior. Female Patients: Sagittal Profile: 79% had a skeletal Class II profile with mandibular retrognathia. Vertical Profile: 47% were hypodivergent with reduced anterior facial height (105°). Dental Relationships: 17% exhibited deep bite, and 48% of those with a Class II profile had increased overjet. 43% were mesofacial, and 10% were dolichofacial. Condyle Position: In Class II hypodivergent and normodivergent females, the condyle was non-concentric and positioned more posteriorly. In hyperdivergent females, the condyle was positioned more anteriorly and higher in the fossa. Conclusion: The study highlighted significant differences in cephalometric parameters and condyle positions between male and female patients with TMD. A posteriorly positioned condyle was associated with a flattened condylar head, particularly in Class II hypodivergent profiles. These findings underscore the importance of individualized diagnostic and treatment approaches based on detailed cephalometric and condylar assessments. Further research is needed to explore the implications of these variations for TMD management and outcomes.

(1) Background: The main objective of this study was to determine the correlation between element and radionuclide activity concentrations and the growth potential of trees across European mountain beech forests; (2) Methods: As, Cd, Co, Cu, Ni, Pb, and Zn were determined using inductively coupled plasma–optical emission spectrometry (ICP/OES). Mercury was determined by Direct Mercury Analyzer DMA 80 Milestone. The Cr, Rb, Sr, Y, Zr, Sn, Ba, and W were determined by Spectro Xepos Energy Dispersive X-ray fluorescence spectrometry (EDXRF). Gamma spectrometry measurements of 22Na, 40K, 232Th, 226Ra, 238U, 235U, and 137Cs were performed using a coaxial High-Purity Germanium (HPGe) detector; (3) Results: The median values of As for the upper and deeper soil horizon were lower, Ni, Pb, Rb, Sr, Y, Zr, Sn, and W were in the range, while the values of Cd, Co, Cr, Cu, Zn, Hg, and Ba were higher than median values given in the Geochemical Atlas of Europe (GAE) for the upper and deeper soil horizon. The radionuclide activity concentrations varied in approximately the same ranges. The production potential of forest trees ranged from 5262.67 for cambisol and umbrisol soil types on granite and limestone parent materials to 24490.78 for umbrisol and rendzina soil types on granite and dolomite parent materials; (4) Conclusions: Parent material had a significant role in the productivity of European mountain beech forests.

A full potential all-electron density functional method within generalized gradient approximation is used to investigate the electronic, elastic and transport properties of cubic copper sulphide and copper selenide. The electronic structure suggests metallic behavior with a zero energy band gap for both materials. Elastic property calculations suggest a stiff material with the bulk to shear modulus ratio of 0.35 and 0.44 for Cu2S and Cu2Se respectively. The transport properties were estimated using the Boltzmann transport approach. Seebeck coefficient, electrical conductivity, thermal conductivity, and power factor all suggest a potential p-type conductivity for Cu2S and n-type conductivity for Cu2Se.

Vegetation identification using remote sensing is essential for understanding terrestrial ecosystems and monitoring climate change. This technology by providing high-resolution images of the Earth's surface from satellites, aircraft, and drones has revolutionized the way scientists study and un-derstand vegetation patterns, providing information on the distribution, structure, and health of plant communities in different regions and biomes. However, identifying vegetation in multi and hyperspectral images remains a difficult, time-consuming, and costly process. Traditional methods for vegetation mapping involve the in-terpretation of spectral indices such as the Normalized Difference Vegetation Index (NDVI), alt-hough they often suffer from limitations such as manual interpretation and limited spatial resolution of satellite images. Furthermore, machine learning techniques, artificial neural networks, decision trees, support vector machines, and random forests have shown promising results in identifying and classifying vegetation cover from hyperspectral images. However, due to the need for per-son-nel with specialized expertise, their application on a large scale is still challenging. On the other hand, correlation methods between curves have emerged as powerful and simplified tool for comparing spectral signatures of hyperspectral image pixels and efficiently classifying vegetation in a study area. Pearson's correlation coefficient and spectral angle mapper are among the most common correlation methods used in vegetation mapping. These correlation methods, among many others available, offer an easily implemented and computationally efficient approach, making them particularly useful for applications in developing countries or regions with limited resources. In this article, a comparative study of correlation/distance metrics was conducted for the detection of vegetation pixels in hyperspectral images. The study allowed for the comparison of five distance and/or correlation metrics: direct correlation, cosine similarity, normalized Euclidean distance, Bray-Curtis’s distance, and Pearson correlation. The two metrics that yielded the best accuracy results in vegetation pixel detection were direct correlation and Pearson correlation. Based on the selected methods, a vegetation detection algorithm was implemented and validated on a hyper-spectral image of the Manga neighborhood in Cartagena de Indias, Colombia. The spectral library was utilized for image processing, while the numpy and scipy libraries in the Python programming language were used for the mathematical calculation of correlations. Both the study's approach and the implemented algorithm aim to serve as a reference for conducting detection studies of various material types in hyperspectral images using open-access programming platforms.

In the field of machine learning, cluster analysis has always been a very important technology for determining useful or implicit characteristics in the data. However, the current mainstream cluster analysis algorithms require comprehensive analysis of the overall data to obtain the best parameters in the algorithm. As a result, handling large-scale datasets would be difficult. This research proposes a distributed related clustering mechanism for Unsupervised Learning, which assumes that if adjacent data are similar, a group can be formed by relating to more data points. Therefore, when processing data, large-scale datasets can be distributed to multiple computers, and the correlation of any two datasets in each computer can be calculated simultaneously. Later, results are processed through aggregation and filtering before assembled into groups. This method would greatly reduce the pre-processing and execution time of the dataset; in practical application, it only needs to focus on how the relevance of the data is designed. In addition, the experimental results show the accuracy, applicability, and ease of use of this method.

To analyse Xuanwei ham flavour quality at different post-ripening times, and to elucidate its microbial diversity, we studied free amino acids and volatile flavouring compounds (VOCs) and their relationships. We determined microbial community changes in Xuanwei ham at 1, 2, 3 and 4 years (W1-4) by high-throughput sequencing, and simultaneously, VOCs and free amino acid contents by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography (LC), respectively. Then heatmap analysis was used to determine correlations between microbial communities, free amino acids and VOCs. A total of 25 free amino acids were detected, among which W3 contained the fewest and most were generally lower than in hams in the other three years. Fifty-nine VOCs were detected, among which were 17 esters, and the highest ester content was found in W4. Atotal of 87508391 reads were obtained from the samples, of which 812844 were clean reads, and the bacterial Chao1 index and Shannon index were significantly higher in W3 than in the other three ham years. In differetly-aged Xuanwei hams, Pseudomonadota was the dominant bacterial phylum, and the most abundant genera were Sarocladium, Klebsiella and Vibrio. Klebsiella was the most abundant genus in W1, and Vibrio in W3, and the second most abundant genera were Sarocladium and Gammaretrovirus. We elucidated differences in Xuanwei ham microflora structures in different years and the main flavor-related microorganisms, thus providing a theoretical basis for subsequent Xuanwei ham storage, quality and improvement.

Phage therapeutics offer a potentially powerful approach to combat multidrug-resistant bacterial infections. However, to be effective, phage therapy must overcome existing and developing phage resistance. While phage cocktails can reduce this risk by targeting multiple receptors in a single therapeutic, bacteria have mechanisms of resistance beyond receptor modification. A rapidly growing body of knowledge describes a broad and varied arsenal of antiphage systems encoded by bacteria to counter phage infection. We sought to understand the types and frequencies of antiphage systems present in a highly diverse panel of Pseudomonas aeruginosa clinical isolates utilized to characterize novel antibacterials. Using web-server tool PADLOC (Prokaryotic Antiviral Defense Locator), putative antiphage systems were identified in these P. aeruginosa clinical isolates based on sequence homology to a validated and curated catalog of known defense systems. Coupling this host bacterium sequence analysis with host range data for 70 phages, we observed a correlation between existing phage resistance and the presence of higher numbers of antiphage systems in bacterial genomes. We were also able to identify antiphage systems that were more prevalent in highly phage-resistant P. aeruginosa strains, suggesting their importance in conferring the resistance.

This work aims at improving surface integrity and LCF life of machined Inconel 718. The correlation between the LCF life of Inconel 718 and various states of machined surface integrity is explored. In this paper, the surface integrity of Inconel 718 specimens is enhanced by low plasticity burnishing (LPB). The LCF life with different surface integrity specimens is predicted by micro-macro finite element method (FEM). Firstly, the LCF specimens with different surface integrity are machined by turning (turned specimen), polishing (matrix specimen) and LPB process (LPBed specimen). Secondly, the LCF experiment is carried out to reveal the effect of surface integrity on LCF life. Finally, the LCF micro-macro FEM model is proposed to predict the LCF of machined Inconel 718 specimens. The representative volume element (RVE) model is established based on the measured surface integrity and microstructure of Inconel 718 specimens. The effect of surface integrity on LCF life is transformed to equivalent load. The micro-macro FEM model combined with Tanaka-Mura dislocation crack initiation theory and extended finite element method (XFEM) is applied to predict the LCF life the machined specimens. The study results show that the LCF life of LPBed specimens can be improved by 90.5% and 36.1% compared with that of turned specimens and polished matrix specimens, respectively. The errors between FEM prediction results and experimental results are 13.1%, 9.2% and 12.2%, respectively. The proposed micro-macro FEM model could be utilized to predict the LCF life of Inconel 718 with different surface integrity, and further to apply the LCF life prediction in industry.

(1) Background: This study aimed to investigate the effect of increased HER-2 expression on tumor-infiltrating lymphocytes (TILs) and determine its impact on the prognosis of colorectal cancer (CRC) patients; (2) Methods: HER-2, CD4, CD8, CD19, LY6G, CD56, CD68, CD11b, and EpCam expression in CRC tissues and adjacent paracancerous tissues were assessed using multiplex fluorescence immunohistochemical staining. The correlation between HER-2 expression and the number of TILs in CRC tissues was analyzed. Kaplan-Meier and Cox proportional hazards models were used to analyze survival outcomes; (3) Results: The expression of HER-2 in tumor tissues was higher than that in paracancerous tissues (1.31 ± 0.45 vs. 0.86 ± 0.20, P < 0.05). Additionally, there was an increase in the numbers of CD4+, CD8+, CD19+, and CD68+ cells in CRC tissues (14.11 ± 1.10 vs. 3.40 ± 0.18, P < 0.005; 0.16 ± 0.12 vs. 0.04 ± 0.04, P < 0.005; 0.71 ± 0.46 vs. 0.25 ± 0.13, P < 0.0005; 0.27 ± 0.24 vs. 0.03 ± 0.11, P < 0.05). The increase in HER-2 expression was positively correlated with an increase in CD4, CD8, and CD19 (p < 0.0001). In HER-2-positive CRC tissues, CD68 expression was increased (0.80 ± 0.55 vs. 0.25 ± 0.22, P < 0.05). In HER-2-upregulated CRC tissues, CD4, CD8, CD19, CD68, CD11b, Ly6G, and CD56 expressions were elevated (0.70 ± 0.37 vs. 0.32 ± 0.17, P = 0.03; 0.22 ± 0.13 vs. 0.09 ± 0.06, P = 0.03; 0.31 ± 0.19 vs. 0.12 ± 0.08, P = 0.02; 1.05 ± 0.62 vs. 0.43 ± 0.21, P < 0.01; 1.34 ± 0.81 vs. 0.53 ± 0.23, P < 0.01; 0.50 ± 0.31 vs. 0.19 ± 0.10, P < 0.01; 1.26 ± 0.74 vs. 0.52 ± 0.24, P < 0.01). Furthermore, increased HER-2 expression is an independent risk factor for recurrence-free survival (RFS) in patients (P < 0.01, HR = 3.421); (4) Conclusions: The increased expression of HER-2 and its relationship with immune cells will provide new insights for immunotherapy in CRC patients.

In this paper, the main physicochemical characteristics and evolutionary laws of microbial community structure during the fermentation of aged vinegar were discussed, and the correlation between Cuqu and microorganisms and physicochemical characteristics during fermentation was explored. The results showed that there are significant differences in genera at different stages of fermentation, the main dominant bacteria in R1 are Bacillus, Lactobacillus, Aspergillus and Issatchenkia. At R2 fermentation stage, Lactobacillus, Acetobacter and Saccharomyces showed an upward trend and finally became absolute advantage bacteria. The main genus of bacteria at the end of overall fermentation is Aspergillus. Correlation analysis shows that in Cuqu, the bacterial genera that are significantly positively and negatively correlated with reducing sugars and amino acid nitrogen are the same, while the bacterial genera that are significantly positively and negatively correlated with pH and saccharification power are the same. During the fermentation process, pH, reducing sugar and saccharification ability are mainly positively correlated with bacterial genera. And research has found that during the fermentation process, the overall correlation between fungal communities and physicochemical characteristics is weaker compared to bacteria.

Physics of high-Tc superconducting cuprates is obscured by the effect of strong electronic correlations. One way to overcome the problem is to seek for an exact solution at least within the small cluster and expand it to the whole crystal. Such an approach is in the heart of the cluster perturbation theory (CPT). Here we develop CPT for the dynamic charge and spin susceptibilities (spin-CPT), within which the correlation effects are explicitly taken into account by the exact diagonalization. We apply spin-CPT to the effective two-band Hubbard model for the cuprates obtained from the three-band Emery model and calculate one- and two-particle correlation functions, namely, spectral function and spin and charge susceptibilities. Doping dependence of the spin susceptibility was studied within spin-CPT and CPT-RPA that is the CPT generalization of the random phase approximation (RPA). Both methods produce the low energy response at four incommensurate wave vectors in qualitative agreement to the results of the inelastic neutron scattering on overdoped cuprates.

Quality monitoring (QM) with CUSUM system can result in potential economy in RMC through optimal control of target strength (by avoiding overdesign) on the one hand and through reduction of producers’ risk against rejection by the client on the other. To overcome the problems associated with the conventional 28-day compressive strength test, correlations are established between accelerated and the standard 28-day cube strength to predict the 28-day strength from the early age strength itself. This paper tried to demonstrate the lack of reliability of single correlation itself along the production time of RMC. The correlations vary with W/C as well as with type of cement. Hence it is demonstrated that correlation is concrete specific. Further, it is also demonstrated that correlation established with specimens having wide variation in the batching may result in poor correlation. Through CUSUM plots of mean and range for cube strength obtained by Monte-Carlo simulation demonstrate the utility of prediction through such correlation in QM and a methodology for monitoring the correlation itself.

The article reviews the constituent’s physico-chemical parameters in the water of the Mansagar Lake of the Jaipur City. The water quality is also investigated using evaluated physico-chemical parameters with in-depth study of their distribution as per sample location-wise and season-wise. A detailed discussion on the associationship among parameters (pH, Conductivity, turbidity, dissolved Oxygen, chemical and Biochemical Oxygen demand, etc.) using the Pearson’s analytical method is also presented. The strength of the article is the graphical presentation of evaluated physico-chemical parameters and the water quality indices for sample station-wise and the season-wise. To our best of understanding, first time such details have been clubbed together and discussion in brief for studied lake.

This current research follows up on Greenleaf’s oft-quoted best test of servant leadership that calls for employees to be better off financially, emotionally, physically, psychologically, etc. because of the time spent with the servant leader. While oft-quoted, little empirical work exists to see if this is true. In this study, 170 participants provided their perception of their supervisors’ level of servant leadership, their perception of the organization’s support, and their self-report of their general well-being. Gender and age bracket information described the participants, and there were no significant differences between gender or age brackets for participants’ perception of their supervisors’ servant leadership. The analysis showed that there was a moderate positive correlation between servant leadership, perceived organizational support, and general well-being. A modification of an existing general well-being instrument provided a new eight-item general well-being scale with a Cronbach’s alpha of 0.956.

This study evaluated the mechanical strengths of three types of orthodontic micro-implants by analyzing their structural configurations. Thirty micro-implants of three types (diameter 1.5 mm, Types A, B, C) were assessed. All micro-implants were manually driven into artificial bones at an 8-mm depth. The insertion torque (IT), pullout strength (PS), and gripping volume (GV) of each type were measured. Intergroup comparisons and intragroup correlation were investigated by statistical analysis. Type B had the greatest inner–outer diameter ratio (0.67), and Type A had the smallest (0.53). The IT of Type A (5.26 Ncm) was significantly (p = 0.038) lower than that of Type C (8.8 Ncm). There was no significant difference in the pullout strength (p = 0.868). The GV of Type A (9.7 mm3) was significant (p < 0.01) greater than Type C (8.4 mm3). Type C was significant (p < 0.01) greater than Type B (7.2 mm3). Spearman’s rho rank correlation test showed that PS of Type B was correlated significantly with GV. In conclusion, the design of thread and its GV were the important factors on the mechanical strengths of micro-implant.

An experimental study is carried out in a cavitation tunnel on a propeller operating downstream of a non-uniform wake. The goal of this work is to establish quantitative correlations between the near pressure field and the cavitation pattern that takes place on the propeller blades. The pressure field is measured at the walls of the test section and in the near wake of the propeller, and is combined with quantitative high-speed image recording of the cavitation pattern. Through simple harmonic analysis of the pressure data and image processing techniques that allow to retrieve the cavitation extension and volume, we discuss the potential sources that generate the pressure fluctuations. Time correlations are unambiguously established between pressure peak fluctuations and cavitation collapse events, based upon the Rayleigh collapse time. Finally, we design a model to predict the cavitation-induced pressure fluctuations from the derivation of the cavitation volume acceleration. This simple model demonstrates a remarkable agreement with the actual pressure field.

Background: pathophysiological changes like low cardiac output (LCO) impact pharmacokinetics, but its extent may be different throughout pediatrics compared to adults. Physiologically based pharmacokinetic (PBPK) modelling enables further exploration. Methods: A validated propofol model was used to simulate the impact of LCO on propofol clearance across age groups using the PBPK platform, Simcyp® (version 19). The hepatic and renal extraction ratio of propofol was then determined in all age groups. Subsequently, dose explorations were conducted under LCO conditions, targeting a 3 µg/mL (80-125%) propofol concentration range. Results: Both hepatic and renal extraction ratios increased from neonates, infants, children to adolescents and adults. The relative change in clearance following CO reductions increased with age, with the least impact of LCO in neonates. The predicted concentration remained within the 3 µg/mL (80-125%) range under normal CO and LCO (up to 30%) conditions in all age groups. When CO was reduced by 40-50%, a dose reduction of 15% is warranted in neonates, infants and children, 25% in adolescents and adults. Conclusions: PBPK driven, the impact of reduced CO on propofol clearance is predicted to be age-dependent, proportionally greater in adults. Consequently, age group specific dose reductions for propofol are required in LCO conditions.

Aim: This analytical cross-sectional study aimed to examine whether there is a correlation between tumor differentiation and certain biomarkers in patients with hepatocellular carcinoma (HCC). Methods: Poorly differentiated (n=443), moderately differentiated (n=379), and well-differentiated (n=272) tumors were separated from the research population, along with a control group (n=364). Biopsies were used to establish the presence of HCC, and biomarker levels were analyzed using chemiluminescence immunoassays in both infected and uninfected individuals. Results: The correlation between age and tumor size was shown to be statistically significant (p0.05) across all subgroups using both descriptive and inferential statistics. Patients with hepatitis C virus and non-A, non-B hepatitis had more advanced tumors than those with other types of poorly differentiated liver cancer. Similarly, individuals with HBsAg and moderate differentiation had bigger tumors, although there was no correlation between hepatitis C and non-A, non-B. Patients with HBsAg or hepatitis C had bigger tumors in the well-differentiated group, albeit the hepatitis C connection was not statistically significant. In addition, the study stressed that tumor size increases with age and that farmers were the most commonly diagnosed profession category. Conclusions: It is clear that early detection in infected populations is crucial for improving HCC outcomes and that chemiluminescence immunoassay has the potential to be a helpful platform for biomarker research. However, the study is limited by its small sample size and its emphasis on only three tumor markers, indicating that more biomarker research is required to improve the accuracy of HCC diagnosis and prognosis.

In developed countries, especially the big-sized ones like Australia and the USA, a car is almost an inevitable necessity to carry out daily activities. Due to this, used cars have become a great alternative to brand new cars because of their cost effectiveness. In this work, estimation of prices of used cars based on numerous factors is studied statistically. Data is based on prices of used cars sold across Australia. Statistical methods like correlation and permutation tests using linear regression model, exact tests and non-parametric bootstrapping is implemented to study the relationship of price with mileage and year of manufacture of the car using p-values and null hypothesis. Predictions are also made on the price by calculating a 95% confidence interval (CI) of median prices in small portions of the dataset. The study presents potential ideas for understanding correlation between variables and parameters in business studies.

(1) This study aimed to examine the prevalence of depression and its correlation with acculturative Stress and Social Connectedness among domestic and overseas students in Japan International University. (2) Methods: A Web-based survey was distributed among students of International University, which resulted in 263 responses. On the survey together with socio-demographic data, a nine-item tool from the Patient Health Questionnaire (PHQ-9), was used to measure the prevalence of Depression and its relationship with socio-demographic data, Social Connectedness Scale was used to measure Social Connectedness, and Acculturative Stress Scale for International Students (ASSIS) was used to measured acculturative stress. (3) Results: Depression was significantly high in international and domestic students (37.81% and 29.85% respectively). English language proficiency and students age (20 years old) showed a significant correlation with depression among domestic students (β=-1.63, p=0.038 and β=2.24, p=0.048). Stay length (third year) also displayed a significant correlation with depression among international students (β=1.08, p=0.032). Among international and domestic students statistically significant positive correlation between depression and acculturative stress, negative associations of social connectedness with depression and acculturative stress were also found. Suicidal or self-hurting ideation thoughts are found among around 20% of all students. (4) Conclusions: These findings indicate a relatively high prevalence of depression among students of International University, and overseas students are more affected. Depression, Acculturation stress and Social Connectedness show statistically strong intercorrelation, which highlights the need of host University to recognise the role of Acculturation and Social Connectedness in the development of Depression among students.

Background: To assess the prevalence of Hypertension (HTN) in Burning Mouth Syndrome (BMS) patients and to investigate its relationship with sociodemographic factors, pain and the psychological profile. Methods: A case-control study was conducted by enrolling 242 BMS patients and 242 controls matched for age and gender. Sociodemographic and clinical characteristics were recorded, and all the participants completed the numeric rating scale (NRS), the short-form of the McGill pain questionnaire (SF-MPQ), the Hamilton rating scale for anxiety and depression (HAM-A, HAM-D), the Pittsburgh sleep quality index (PSQI) and the Epworth sleepiness scale (ESS). Results: The BMS patients presented a statistically significant higher prevalence of HTN compared to the controls (55% versus 33.5%; p-value: &lt;.001**) and higher median scores of the NRS, SF-MPQ, HAM-A, HAM-D, PSQI and ESS (p &lt; .001**). Multivariate regression analysis in the BMS patients indicated positive correlations between HTN and age, systemic diseases, drug consumption and anxiety (p-value: &lt;.001**) and these predictors were responsible for 11.3% of the HTN variance in the BMS patients, when considered together. Conclusions: The prevalence of HTN was significantly higher in the BMS patients, since ageing, the presence of comorbidities, drug consumption and anxiety were potential predictors. Further studies are needed to better investigate the relationship between BMS and HTN.

With the rapid development of Internet and the widely usage of smart devices, massive multimedia data are generated, collected, stored and shared on the Internet. This trend makes cross-modal retrieval problem become a hot issue in this years. Many existing works pay attentions on correlation learning to generate a common subspace for cross-modal correlation measurement, and others uses adversarial learning technique to abate the heterogeneity of multi-modal data. However, very few works combine correlation learning and adversarial learning to bridge the inter-modal semantic gap and diminish cross-modal heterogeneity. This paper propose a novel cross-modal retrieval method, named ALSCOR, which is an end-to-end framework to integrate cross-modal representation learning, correlation learning and adversarial. CCA model, accompanied by two representation model, VisNet and TxtNet is proposed to capture non-linear correlation. Beside, intra-modal classifier and modality classifier are used to learn intra-modal discrimination and minimize the inter-modal heterogeneity. Comprehensive experiments are conducted on three benchmark datasets. The results demonstrate that the proposed ALSCOR has better performance than the state-of-the-arts.

The number of SIEM introduction is increasing in order to detect threat patterns in a short period of time with a large amount of structured/unstructured data, to precisely diagnose crisis to threats, and to provide an accurate alarm to an administrator by correlating collected information. However, it is difficult to quickly recognize and handle with various attack situations using a solution equipped with complicated functions during security monitoring. In order to overcome this situation, new detection analysis process has been required, and there is an effort to increase response speed during security monitoring and to expand accurate linkage analysis technology. In this paper, reflecting these requirements, we design and propose profiling auto-generation model that can improve the efficiency and speed of attack detection for potential threats requirements. we design and propose profiling auto-generation model that can improve the efficiency and speed of attack detection for potential threats.

The level of development of the innovation factor plays a crucial role in supporting the high-quality development of China's economy. To advance the development of regional innovation factor allocation efficiency along the Belt and Road. This article introduces the super-efficiency SBM-DEA-Malmquist model for the static and dynamic analysis of innovation factor allocation efficiency in 17 provinces along the Belt and Road from 2012 to 2021. The Moran index model analyzes the spatial correlation. The results show that: (1) The overall innovation factor allocation efficiency along the Belt and Road is not high, and there are obvious differences among different regions. The eastern region is the highest compared to other regions. (2) According to the efficiency decomposition results, pure technical efficiency is the main reason for the low innovation factor allocation efficiency. (3) Through the Malmquist index and decomposition index, it is found that pure technical efficiency and scale efficiency are key factors in improving technical efficiency. (4) The analysis of spatial correlation reveals a strong spatial agglomeration feature among the provinces along the Belt and Road. The innovation factor allocation efficiency is mainly manifested in the L-L type. Finally, according to the analysis results, suggestions and policies are put forward to improve the innovation factor allocation efficiency in the regions along the Belt and Road.

Digital Image Correlation (DIC) is an optical technique used to measure surface displacements and strains in materials and structures. This technique has demonstrated significant utility in structural examination and monitoring. This manuscript offers a comprehensive review of contemporary research and applications that have leveraged the DIC technique in laboratory-based structural tests. The reviewed works encompass a broad spectrum of structural components, such as concrete beams, columns, pillars, masonry walls, infills, composite materials, structural joints, steel beams, slabs, and other structural elements. These investigations have underscored the efficacy of DIC as a metrological instrument for precise quantification of surface deformation and strain in these structural components. Moreover, the constraints of the DIC technique have been highlighted, especially in scenarios involving extensive or complex test configurations. Notwithstanding these constraints, the DIC methodology has validated its effectiveness as a strain measurement instrument, offering numerous benefits such as non-invasive operation, full-field measurement capability, high precision, real-time surveillance, and compatibility with integration into other measurement instruments and methodologies.

The purpose of the investigation was to determine the relationship between rotary kiln liner loss and steel structure ovality. As measurement apparatus, a terrestrial laser scanner was used. The interior and exterior of the rotary kiln were measured. The primary focus object was inner-lining loss and the geometric characteristics of cylindrical shells. The research uncovered significant disparities in inner lining loss between sections. A correlation was found between ovality and elimination of inner lining. Due to the hypothesis of constant inner linig loss from the middle of the rotary kiln, the investigation found that the loss of brick lining was less than the value reported from the boreholes. The study offers significant information on maintenance and repair strategies for rotary kilns, which have the potential to increase their efficiency and useful life.

Cosmic strings can arise from spontaneous phase transitions during the inflationary period and are describable as disclination topological defects in spacetime. Analytical integration of the geodesic equations for a particle around a cosmic string reveals distinct orbit patterns dependent on the disclination intensity $\beta_{0}$. After its interaction with the cosmic string, the particle's behavior becomes random. To categorize these patterns, we describe the geodesic motion as iterated maps of a discrete parameter. Through the stabilization values of these functions, we correlate the scattering angle and the number of loops for the particle with $\beta_{0}$. Therefore, we interpret the gravitational field mathematically as an instructor of a particle's next position, given its previous one. We find that the radial function in the small displacement limit is similar to the logistic map. This leads us to conjecture the potential of the discrete parameter being a multiple of Planck's time, suggesting a method for the geometric discretization of spacetime around a cosmic string.

This study investigates the frequency dependence of the correlation or anticorrelation of ozone and temperature in the middle atmosphere. The anticorrelation of ozone and temperature plays a role for the expected recovery or superrecovery of upper stratospheric ozone in presence of manmade cooling of the middle atmosphere due to increasing carbon dioxide emissions. The correlation between lower stratospheric ozone and temperature indicates the dependence of lower stratospheric temperature trends on the ozone evolution in addition to greenhouse gas emissions. Ozone and temperature measurements of the microwave limb sounder (MLS) on the satellite Aura from 2004 to 2021 are utilized for Bern (46.95∘N, 7.44∘E) at middle latitudes and for the equator region. The time series are bandpass filtered for periods from 2 days to 5 years. The correlation coefficient depends on the period of the oscillation in temperature and ozone. The strongest correlation and anticorrelation are found for the annual oscillation. The anticorrelation between ozone and temperature in the upper stratosphere is about −0.7 at a period of 2 days and −0.99 at a period of one year. Thus, the temperature dependence of the ozone reaction rates also leads to an anticorrelation of ozone and temperature at short periods so that ozone can be considered as a tracer of planetary waves. At the equator, a dominant semiannual oscillation and an 11 year solar cycle are found for nighttime ozone in the upper mesosphere. The SAO in ozone and temperature show a strong correlation indicating a dynamical control of the ozone SAO in the upper mesosphere. The SAO in the equatorial nighttime values of ozone and temperature is due to a semiannual modulation of vertical advection by the diurnal tide.

To explore the spatial network structure characteristics and driving effects of carbon emission intensity in China's construction industry, the investigation combined the modified gravity model and social network analysis method to deeply analyze the spatially associated network structure characteristics and driving effects of carbon emission intensity in China's construction industry, based on the measurement of carbon emission data of China's construction industry from 2006 to 2017. The results show that the regional differences of carbon emission of construction industry are significant, and the carbon emission intensity of construction industry show a fluctuation trend. The overall network of carbon emission intensity shows an obvious “core-edge” state, the hierarchical network structure is gradually broken. Economically developed provinces generally play a leading role in the network, and play an intermediary role to guide other provinces to develop together with them. Among the network blocks, most of the blocks play the role of “brokers”. The block with the leading economic development has a strong influence on the other blocks. The increase of network density, the decrease of network hierarchy and network efficiency will reduce the construction carbon emission intensity.

Background: Essential hypertension is a major public health associated with increase pressure on the vascular walls and red blood cells (RBCs). In the present work, osmotic fragility (OF) of RBCs was reexamined in the means of its correlation with two risk factor; iron status and lipid profile. Experimental: OF, iron status parameters, and lipid profile components were measured in 60 patients and compared with the results of 30 controls. Results: The results showed a significant increase in all iron indices of hypertensive patients in comparing with healthy control group except TIBC, UIBC, and transferrin concentrations, which decrease in these patients in comparing with control group. Serum TGs, total cholesterol, VLDLc, and LDLc were increased while there is no significant in serum HDLc in patients to comparing with control group. There is no significant change in OF between patients and controls where p=0.173. The iron status parameters and lipid profile components were dependent on sex and smoking state. Hemoglobin and PCV were correlated significantly with total cholesterol and LDLc. Transferrin saturation showed a positive correlation with cholesterol, LDLc, and TGs, but negatively correlated with HDL_c. No significant correlation between all the measured parameters and OF in HT patients. There is a significant correlation between serum ferritin and systolic BP and between Hb and systolic BP. Conclusion: No significant effect on the OF in HT patients. HT patients have elevated level of iron parameters in comparing with controls. OD has no correlation with iron status parameters or with lipid profile components.

Currently the rapid growth of global economy has the competition among high-tech industries develop from regional to global, and the competition becomes fierce. In face of such fierce competition in global high-tech industry, it is realized that tangible assets could no longer be the differentiation basis, but intangible assets are regarded as the differentiation capital. An enterprise with sustainable innovation would dominate the world market and enhance the international competitiveness of domestic economy. When internal entrepreneurial culture is prevalent, an enterprise would naturally promote the innovation capability. Such a point of view also explains more popular of the innovative products or services of some enterprises than those with larger scales. Aiming at employees in high-tech industry in Guanxi Province, total 500 copies of questionnaire are randomly distributed, and 337 valid copies are retrieved, with the retrieval rate 67%. The research results reveal significantly positive correlations between 1.entrepreneurial culture and sustainable innovation capability, 2.sustainable innovation capability and patent, and 3.entrepreneurial culture and patent. According to the results, suggestions are proposed, expecting to explain how a high-tech business outperforms in the changeable digital era and acquires the sustainable innovation capability and patent to grasp the opportunity.

Background: Many clinical conditions are affected by meteorological factors and climate changes. Psychiatric disorders are large contributors to the global disease burden, but the literature on the impact of climate changes on mental health is limited. The aim of this study is to investigate the correlation between rising temperatures and admissions for acute exacerbations of psychiatric disorders. Methods: Data were collected for summer months of years 2013 to 2022. Mean monthly tempera-tures were obtained from the meteorological station of the Department of Physics of the Universi-ty of Turin. Data on patients admitted to the acute psychiatric unit of San Luigi Gonzaga Univer-sity Hospital (Turin, Italy) were extracted from the hospital registry. Linear regression analyses were used to investigate the correlation between temperature and number of admissions. Results: A total of 1600 admissions to our psychiatric ward were recorded. Mean monthly temper-ature and monthly number of admissions were directly correlated (P = 0.0020). The correlation between temperature and admissions was significant for the subgroup of admissions due to Bipo-lar Disorders (BD) (P=0.0011), but not for Schizophrenia (P=0.6070) (SCZ) or Major Depressive Disorder (MDD) (P=0.0588). Conclusions: These results confirm the impact of meteorological factors on mental disorders, and in particular on the course of BD. This provides new insights into etiopathological mechanisms and can contribute to improved follow up and relapse prevention.

The outbreak of the COVID-19 pandemic has raised concerns about potential environmental factors that could influence the spread and severity of the SARS-CoV-2 virus. Atmospheric pollution, particularly particulate matter (PM), has been suggested as a contributing factor to viral infections and respiratory complications. This two-year observational study aimed to investigate the relation between air pollution and the spread of COVID-19, focusing on PM2.5. Unlike previous studies limited to specific cities or countries, inevitable to use temporal data. Our research analyzed data from various states across the United States, considering both spatial and temporal correlation. The analysis considered the number and geographic distribution of COVID-19 cases along with daily PM2.5 exposure levels, accounting for monthly average PM2.5 exposure, from March 2020 to December 2021. The observed conflicting results of the temporal and spatial correlation present challenges for researchers in understanding the true nature of the relationship between PM2.5 air pollution and COVID-19 cases. The correlation between various factors, such as population density, PM2.5, temperature, and wind speed, and COVID-19 refers to an association or statistical relationship, not causation. Moreover, the intricate interplay of these variables makes it difficult to establish a clear cause-and-effect relationship.

The heat and matter transfer during glucose catabolism in living systems and their relation with entropy production are a challenging subject of the classical thermodynamics applied to biology. In this respect, an analogy between mechanics and thermodynamics has been performed via the definition of the entropy density acceleration expressed by the time derivative of the rate of entropy density and related to heat and matter transfer in minimum living systems. Cells are regarded as open thermodynamic systems that exchange heat and matter resulting from irreversible processes with the intercellular environment. Prigogine’s minimum energy dissipation principle is reformulated using the notion of entropy density acceleration applied to glucose catabolism. It is shown that, for out-of-equilibrium states, the calculated entropy density acceleration is finite and negative and approaches as a function of time a zero value at global thermodynamic equilibrium for heat and matter transfer independently of the cell type and the metabolic pathway. These results could be important for a deeper understanding of entropy generation and its correlation with heat transfer in cell biology with special regard to glucose catabolism representing the prototype of irreversible reactions and a crucial metabolic pathway in stem cells and cancer stem cells.

Objective: Infliximab (IFX) concentrations are a predictive factor (PF) of pharmacokinetic (PK) origin in the treatment of Crohn’s disease (CD). We evaluated clearance, another PF of PK origin, either alone or in combination with concentrations. Methods: PF of PK origin were evaluated from two cohorts, the first received standard dosing (n=37), and the second was designed to proactively target therapeutic IFX concentrations (n=108). Concentrations were measured using homogenous mobility shift assay. Clearance was estimated using nonlinear mixed effects methods with Bayesian priors. C-reactive protein based clinical remission (<3mg/L in the absence of symptoms) was used for the disease control outcome. Longitudinal changes in disease control due to factors including time, IFX concentration, and clearance were analyzed using repeated event analysis. Change in objective function value (∆OFV) was calculated to compare concentration and clearance. Results: Lower baseline clearance and proactive dosing associated with enhanced disease control during induction (p<0.01). Higher IFX concentrations and lower Clearance measured at the second, third and fourth infusion yielded improved disease control during maintenance (p<0.032). During maintenance, the association with disease control was better with clearance than with concentrations (∆OFV= -19.2; p<0.001), and the combination of both further minimized OFV (p<0.001) with markedly improved clinical yield in the presence of both PF of PK origin. Conclusion: PF of PK origin and lower clearance during induction and maintenance yielded enhanced disease control in pediatric CD treated with IFX. The combination of IFX concentration and clearance are better predictors of therapeutic outcome compared to either one alone.

This study analyzed eye examination data from the 5th Korea National Health and Nutrition Examination Survey to investigate the relationship between cataract prevalence and sunlight exposure among Koreans. Out of 952 individuals from 192 districts surveyed from January to December, statistical analyses using SPSS version 26, including chi-square tests and logistic regression, were conducted. Results: Results showed that the incidence of cataracts was higher in people exposed to sunlight for more than 5 hours. Regarding gender, the incidence of cataracts was higher in female in the 2-5 hours of sunlight exposure group, and in male in the group exposed to sunlight for more than 5 hours. Age significantly increased cataracts after age 45 in both groups. Additionally, the prevalence was higher among college graduates in the 2 to 5 groups, and among elementary school graduates in the more than 5 hours usage group. In urban areas, the cataract prevalence rate was higher in the 2-5-hour usage group, and in rural areas, the cataract prevalence was higher in the more than 5-hour usage group. In conclusion, prolonged sunlight exposure, particularly over 5 hours, correlated with higher cataract prevalence among Koreans, with various demographic factors influencing incidence rates.

The study of angular correlations of heavy-flavor particles in hadronic collisions can provide crucial insight into the heavy-quark production, showering and hadronization processes. The comparison with model predictions allows us to discriminate among different approaches for heavy-quark production and hadronization, as well as different treatments of the underlying event employed by the models to reproduce correlation observables. In ultra-relativistic heavy-ion collisions, where a deconfined state of matter, the quark-gluon plasma (QGP), is created, heavy-flavor correlations can shed light on the modification of the heavy-quark fragmentation due to interaction of charm and beauty quarks with the QGP constituents, as well as characterize their energy loss processes while traversing the medium. Insight into possible emergence of collective-like mechanisms in smaller systems, resembling those observed in heavy-ion collisions, can also be obtained by performing correlation studies in high-multiplicity proton-proton and proton-nucleus collisions. In this review, the most recent and relevant measurements of heavy-flavor correlations performed in all collision systems at the LHC and RHIC will be presented, and the new understandings that they provide will be discussed.