Hutchison-Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder caused by the mutant protein progerin, which is expressed by the abnormal splicing of LMNA gene. HGPS affects systemic levels, except cognition or brain development in children, showing that cellular aging can occur in the short term. However, the causes of aging that humanity is working to overcome remain poorly understood. Studying progeria could be useful for unraveling the causes of human aging (as well as fatal age-related disorders). Elucidating the clear cause of HGPS or the development of a therapeutic medicine will provide inconceivable comfort for young patients and enable them to live a normal life. This review aimed to: i) briefly describe how progerin was discovered as the causative agent of HGPS, ii) elucidate the puzzling observation of the absence of primary neurological disease in HGPS, iii) present several studies showing the deleterious effects of progerin and the beneficial effects of its inhibition, and iv) summarize research to develop a therapy for HGPS, and introduce clinical trials for its treatment.

Malnutrition and dental caries in early childhood remain persistent and intertwined global health challenges, particularly for indigenous and geographically-remote populations. To examine the prevalence and associations between early childhood dental caries, parent-reported mouth pain and malnutrition in the Amazonian region of Ecuador, we conducted a cross-sectional study of the oral health and nutrition status of 1,407 children from birth through age 6 in the “Alli Kiru” program (2011-2013). We used multivariate regression analysis to examine relationships between severe caries, parent-reported mouth pain measures, and nutritional status. The prevalence of dental caries was 65.4%, with 44.7% of children having deep or severe caries, and 33.8% reporting mouth pain. The number of decayed, missing and filled teeth dmft) increased dramatically with age. Malnutrition was prevalent, with 35.9% of children stunted, 1.1% wasted, 7.4% underweight, and 6.8% overweight. As mouth pain increased in frequency, odds for severe caries increased. For each unit increase in mouth pain frequency interfering with sleeping, children had increased odds for underweight (AOR: 1.27; 95% CI: 1.02 – 1.54) and decreased odds for overweight (AOR: 0.76; 95% CI: 0.58 – 0.97). This relationship was most pronounced among 3-6 year-olds. Early childhood caries, mouth pain and malnutrition were prevalent in this sample of young children. Parent-reported mouth pain was associated with severe caries, and mouth pain interfering with sleeping was predictive of poor nutritional status. We demonstrate the utility of a parsimonious parent-reported measure of mouth pain to predict young children’s risk for severe early childhood caries and malnutrition, which has implications for community health interventions.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron and over time the cystic dilatation lead to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts lead to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and haematuria. However, the presentation of ADPKD varies in children from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset of ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide the clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra normal kidney function we explored the glomerular filtration rates dynamics and the renal ultrasound adjusted percentiles. 14 out of 16 patients had kidney percentile over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 ml/min/1.73m2 compared to Schwartz eGFR 126.28 ± 33.07ml/min/1.73m2, p=0.14). Also, when the quadratic equation was employed, not even a patient reached the glomerular hyperfiltration thresholds. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1-year of follow-up (Quadratic ΔeGFR=0.32±5.78ml/min/1.73m2) as opposed to Schwartz formula that can falsely classify children in a hyperfiltration state ΔeGFR=7.51±19.46ml/min/1.73m2), p=0.019.

Ethiopia has decades of experience in implementing land and water management interventions. Nonetheless, there remains persisting challenges to follow an adaptive management (AM) approach in efforts of restoring and transforming agricultural landscapes. This review was carried out to synthesize evidences on the impact on agricultural landscapes following the implementation of land and water management practices and to evaluate the use of AM approaches. We explored how elements of the structures and functions of landscapes have been transformed, and how the components of AM, such as structured decision-making and learning processes, have been applied. Despite numerous environmental and economic benefits of land and water management interventions in Ethiopia, this review revealed gaps in AM approaches. These include: (i) insufficient efforts in relation to evidence based contextualization of interventions, (ii) insufficient efforts in monitoring of bio-physical and socio-economic processes and changes post implementation, (iii) lack of trade-off analyses, and (iv) inadequacy of local community engagement and provision of feedback. Given the many uncertainties we must deal with, efforts to restore and transform agricultural landscapes cannot follow a business-as-usual approach. Future investment, in AM approach, tailored to the needs and context would help to achieve the goals of sustainable agricultural landscape transformation. The success depends on three interdependent pillars of action: the ability to make a robust, co-developed plan of interventions, the ability to continuously monitor changes based on key variables, and to learn from the knowledge generated and apply the learning as implementation evolves.

Recently, doubts were raised about the existence of the bilingual advantage in cognitive control. The aim of the present review was to investigate the bilingual advantage and its modulating factors. We searched the Medline, ScienceDirect, Scopus, and ERIC databases for all original data and reviewed studies on bilingualism and cognitive control, with a cut-off date of October 31, 2018, thereby following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol. The results of the 46 original studies show that, indeed, the majority, 54.3%, reported beneficial effects of bilingualism on cognitive control tasks; however, 28.3% found mixed results, and 17.4% found evidence against its existence. Methodological differences seem to explain these mixed results: particularly, the varying selection of the bilingual participants, the use of non-standardized tests, and the fact that individual differences were often neglected, and that longitudinal designs were rare. Therefore, a serious risk for bias exists in both directions (i.e., in favor of and against the bilingual advantage). To conclude, we found some evidence for a bilingual advantage in cognitive control; however, if significant progress is to be made, better study designs, bigger data, and more longitudinal studies are needed.

The present study was performed to examine that transforming growth factor beta (TGF-β) in root-surrounding tissues on deciduous teeth during the physiological root resorption regulates the differentiation induction into odontoclast. We prepared root-surrounding tissues with (R) or without (N) physiological root resorption scraped off at three regions (R1-R3 or N1-N3) from the cervical area to the apical area of the tooth and measured both TGF-β and the tartrate-resistant acid phosphatase (TRAP) activities. The TGF-β activity level was increased in N1-N3, whereas the TRAP activity was increased in R2 and R3. In vitro experiments for RANKL-mediated osteoclast differentiation revealed that TGF-β in N1-N3 and R1-R3 enhanced the TRAP activity in RAW264 cells. A genetic study indicated that the mRNA level of TGF-β1 in N1 and N2 was significantly increased, and corresponded with that of osteoprotegerin (OPG). In contrast, the expression level of receptor activator of NF-κB ligand (RANKL) was increased in R2 and R3. Our findings suggest that TGF-β is closely related to the regulation of OPG induction and RANKL-mediated odontoclast differentiation depending on the timing of RANKL and OPG mRNA expression in the root-surrounding tissues of deciduous teeth during physiological root resorption.

This research explores the feasibility of a data-driven optimization algorithm for placing sparse arrays of artificial hair-cell airflow velocity sensors to enable agile and robust flight-by-feel control of unmanned aircraft. The Sparse Sensor Placement Optimization for Prediction (SSPOP) algorithm exploits the information-rich features of large flow datasets to find a near-optimal set of locations for flow sensors on a wing. The flow information from these sensors can be used to predict flight state parameters such as the angle of attack, mimicking the fly-by-feel control systems observed in nature. We evaluate the effectiveness of this approach for a blunt-edged 45∘ swept delta wing. Exploiting the information in the complex airflow patterns over this wing, the SSPOP algorithm selects a sensor location design point (DP) which reliably ranks within the top 1% of all possible DPs by root mean square error in angle of attack prediction. This performance was consistent across models of various artificial hair lengths, and one model with variable hair lengths. This bioinspired dimension-reducing method for sensor placement optimization exhibits reliability and flexibility benefits when compared with a conventional greedy search algorithm and gradient-based optimization using auto-differentiation. The successful application of SSPOP in complex 3D flows paves the way for experimental evaluation of data-driven sparse sensor placement optimization for artificial hair-cell airflow sensors and is a major step toward biomimetic flight-by-feel.

Porous β-tricalcium phosphate (Ca3(PO4)2; β-TCP) was prepared by freeze-drying and the effects of this process on pore shapes and sizes were investigated. Various samples were prepared by freezing β-TCP slurries above a liquid nitrogen surface at −180 °C with subsequent immersion in liquid nitrogen at −196 °C. These materials were then dried under reduced pressure in a freeze-dryer after which they were sintered by heating. Compared with conventional heat-based drying, the resulting pores were more spherical, which increased both the mechanical strength and porosity of the β-TCP. These materials had a wide range of pore sizes from 50 to 200 µm, with the mean and median values both approximately 100 µm regardless of the freeze-drying conditions. Mercury porosimetry data showed that the samples contained small, interconnected pores with sizes of up to 1.24 µm and macroscopic, interconnected pores up to 25.8 µm in size. The effects of non-ionic surfactants having different hydrophilic/lipophilic balance (HLB) values on foaming and pore size were also investigated. Materials made with surfactants having lower HLB values exhibited smaller pores and lower porosity whereas higher HLB surfactants gave higher porosity and slightly larger macropores. Even so, the pore diameter could not be readily controlled solely by adjusting the HLB value. The findings of this work indicated that high porosity (75%) and good compressive strength (>2 MPa) can both be obtained in the same porous material and that foaming agents with HLB values between 12.0 and 13.5 were optimal.

Observe the synergistic effect and dose-effect relationship of Trimethoprim (TMP) on bactericidal activity with Flos Lonicerae in vitro. Microamount chessboard dilution method was conducted to determine the minimal inhibitory concentration (MIC) of Trimethoprim, Flos Lonicerae, as well as the combination of Trimethoprim and Flos Lonicerae separately against Staphylococcus aureus, Escherichia coli in vitro and Salmonella. The pour plate count method was used to determine the combined bactericidal activity of Flos Lonicerae combined with Different concentrations TMP. The results showed that the MIC values of the combination of Flos Lonicerae with TMP was much less than the MIC values of the independent use of Flos Lonicerae or TMP, The FIC values of the combination of Flos Lonicerae with TMP were between 0.5 and 1, there was additive effect between them. The bactericidal rates were fitted with least square method, the 95% confidence intervals of the optimal blending quantity about the combination of Flos Lonicerae with TMP on the test organisms were 231μg·mL^-1-249μg·mL^-1, 237μg·mL^-1-259μg·mL^-1, and 235 -259μg·mL^-1

The general synthesis of boron-containing cyclic compounds (boracycles) necessitates toxic organotin precursors or highly reactive boron halides. Here we report the synthesis of seven- and five-membered boracycles utilizing arylboronic acid pinacol esters (ArBpins) as stable boron sources. Grignard reagents generated from 2,2′-dibromodibenzyl or 2,2′-dibromobiphenyl reacted with ArBpins, where Ar = 9-anthryl (Anth), 2,4,6-trimethylphenyl (Mes), 2,4,6-triisopropylphenyl (Tip), to give 10,11-dihydro-5H-dibenzo[b,f]borepins or dibenzoborole derivatives. This Bpin-based method was successfully applied to a one-shot double boracycle formation, providing a dihydrodibenzoborepin–anthracene–dihydrodibenzoborepin triad molecule in a good yield. The dihydrodibenzoborepin bearing the Anth group was directly converted to the unsaturated borepin by NBS/AIBN. All products were characterized by NMR, HRMS, and in some cases, single-crystal X-ray diffraction analysis. Additionally, the photophysical properties of the products are also reported.

Acoustic focusing of particle flow in microfluidics has been shown to be an efficient tool for particle separation for various chemical and biomedical applications. The mechanism behind the method is the selective effect of the acoustic radiation force on distinct particles. In this way, they can be selectively focused and separated. The technique can also be applied under stationary conditions, i.e., in the absence of fluid flows. In this study, the manipulation of self-propelled particles, such as Janus particles, in an acoustofluidic setup is investigated. In experiments with self-propelled Janus particles and passive beads, we explore the interplay between self-propulsion and the acoustic radiation force. Our results demonstrate unusual and potentially useful effects such as selective trapping, escape and assisted escape in binary mixtures of active and passive particles. We also analyze various aspects related to the behavior of Janus particles in acoustic traps in the presence and absence of flows.

Aquaporin-11 (AQP11) is an intracellular water channel expressed at the endoplasmic reticulum (ER) of the kidney proximal tubule. Its gene disruption in mice leads to intracellular vacuole formation at one week old and the subsequent development of polycystic kidneys at three week old. As the damaged proximal tubular cells with intracellular vacuoles later form cysts, autophagy may play a role in their survival. We examined the autophagy activity before and after the development of cysts in AQP11(-/-) kidneys. We first observed an enhanced expression of LC3 gene (Map1lc3b) as well as other autophagy-related genes in AQP11(-/-) mice by quantitative PCR analysis. We then examined the formation of autophagosomes visualized by a green fluorescent fusion protein, GFP–LC3 in its transgenic mice. The expression of GFP-LC3 puncta was increased in the proximal tubule of AQP11(-/-) mice before the cyst formation. Interestingly, they were also observed in the cyst-lining epithelial cell. Further PCR analyses revealed the enhanced expression of apoptosis- and ER stress-related caspase genes before and after the cyst formation suggesting that ER stress may have enhanced autophagy. We conclude that autophagy will play an important role in the development and the survival of the kidney cysts in AQP11(-/-) mice.

Current treatments in patients with pancreatic cancer offer limited benefits. In this report, we applied “alkalization therapy”, which was efficacious for other solid tumors at our clinic, to stage 4 pancreatic cancer patients, and investigated its effect on disease prognosis. Patients with metastatic pancreatic cancer who were treated at Karasuma Wada Clinic in Kyoto, Japan, between 2011 and 2022 were included in the study. All patients received alkalization therapy (combination of an alkaline diet, bicarbonate, and citric acid administration), alongside standard chemotherapy. Urine samples were collected to assess urine pH as a marker for whole-body alkalization. In the 98 patients analyzed, the median overall survival (OS) from the time of diagnosis was 13.2 months. Patients with a mean urine pH of 7.5 or greater had a median OS of 29.9 months, compared with 15.2 months for those with a mean urine pH of 6.5 to 7.5, and 8.0 months for those with a mean urine pH of less than 6.5, which suggests a trend of a longer OS in patients with a higher urine pH. Conclusions: Alkalization therapy may offer a viable approach to enhance the survival of stage 4 pancreatic cancer patients, who typically have an unfavorable prognosis.

The social, environmental and scientific significance of the urban climate has shaped a research stream at Universitat Jaume I’s Climate Lab. Previous research has found higher temperature trends at urban observatories. This study examines in depth the features of the urban environment and the thermal behaviour of land use and land cover and the changes which have taken place. The CORINE Land Cover database was used to delimit the primary Land Use Land Cover (LULC) and its changes between 1990 and 2018. Once this had been established, land surface temperatures (LSTs) between 1985 and 2023 were retrieved from the Landsat database available on the Climate Engine website. Analysis of the primary land cover showed the greatest thermal increase in artificial surfaces, especially in industrial, commercial and transport units which are common on their outskirts. These areas also have the highest temperatures on a monthly basis with the biggest differences occurring in the summer. The results are less clear for urban fabrics and agricultural areas due to their diversity and complexity. The study concludes that urban growth and its commercial and industrial environment has an undeniable effect on the temperatures recorded by urban observatories and enables better decision-making when setting up weather stations for a more detailed time study of the urban heat island (UHI).

This paper introduces in general the conservation work of the Nara Palace Site in Japan carried out by Japanese conservation experts. Concerning conservation theory, this paper focused on the international conventions in which the 1994 Nara Document on Authenticity plays an important role in contributing to Japanese cultural heritage conservation achievements with the expansion of Cultural diversity and Heritage diversity, the Values and Authenticity conceptions which proposed a new orientation in terms of awareness and openness broader vision in identifying architectural heritage values. Regarding, based on the 1994 Nara Document on Authenticity, the 1964 Venice Charter, and the 1999 Bura Charter, we try to propose a new concept of the so-called “Architectural Heritage DNA” and its potential structure, providing a simple formula for the authentic values appraisal of the heritage conservation works. In addition, we also try to supplement the concept of Inheritance between Conservation and Development which is the lack of international conventions of cultural heritage conservation. The viewpoints expressed in this paper are based on the most common concepts of international conventions but interpreted in a new-understandable, practical, and highly applicable way possible to the current socio-political situation and in the future, as well.

The difficulty in the clinical diagnosis of labor is due to an evolutionary mismatch. The ability to hide the signs and symptoms of labor is an evolutionary trait that was once advantageous, but became maladaptive due to environmental changes. Prospective diagnosis of labor is not possible with certainty using only clinical criteria; however, by analyzing the urinary metabolome of women in labor, this diagnosis is likely possible in all cases. In this review, we explain why the two methods (clinical and metabolomic) differ in efficacy and sensitivity, and we try to fit this difference into an evolutionary framework that explains these discrepancies considering evolutionary mismatch. The study of metabolomics allows the truth to emerge from the past, and the diffusion of metabolomic techniques and their application to clinical reality in the form of POC (Point of Care) could change the management of labor and childbirth in the future.

The main ideas of F-transform came from representing expert rules. It would be therefore re reasonable to expect that the more accurately the membership functions describe human reasoning, the more efficient will be the corresponding F-transform formulas. We know that an adequate description of our reasoning corresponds to complicated membership functions -- however, somewhat surprisingly, most efficient applications of F-transform use the simplest possible triangular membership functions. There exist some explanations for this phenomenon which are based on local behavior of the signal. In this paper, we supplement this local explanation by a global one: namely, we prove that triangular membership functions are the only one that provide the accurate description of appropriate global characteristics of the signal.

The pathology of idiopathic intracranial hypertension (IIH), a disease characterized by papillary edema and increased intracranial pressure (IICP), is not yet understood; this disease significantly affects quality of life due to symptoms, including vision loss, headache, and pulsatile tinnitus. By contrast, superficial siderosis (SS), a disorder in which hemosiderin is deposited on the surface of the cerebral cortex and cerebellum, potentially causes cerebellar ataxia or hearing loss. So far, no cases of IIH with infratentorial and supratentorial cortical SS have been reported. Herein, we report a case of a 31-year-old woman with obesity who developed this condition. The patient suddenly developed headache and dizziness, had difficulty walking, and subsequently became aware of diplopia. Fundus examination revealed bilateral optic nerve congestive papillae and right eye abducens disturbance. Head magnetic resonance imaging (MRI) showed prominent SS on the cerebellar surface and cerebral cortex. Lumbar puncture revealed IICP of 32 cmH2O, consistent with the diagnostic criteria for IIH, and treatment with oral acetazolamide was started; subsequently, the intracranial pressure decreased to 20 cmH2O. Her abduction disorder disappeared, and the swelling of the optic papilla improved. She was now able return to her life as a teacher without any sequelae. SS is caused by persistent slight hemorrhage into the subarachnoid space. In this case, both infratentorial and supratentorial cortical superficial SS was observed. Although cases of IIH complicated by SS are rare, it should be kept in mind that a causal relationship between IIH and SS was inferred from our case. Our findings also suggest that cerebrospinal fluid dynamic analysis using MRI is effective in diagnosing IIH and in determining the efficacy of treatment.

Simple Summary: The distribution of typical bacterial redox enzymes such as pyruvate-ferredoxin oxidoreductase (PFOR) in protozoa remains interestingly puzzling. Previous studies have demonstrated diverse cellular localizations of PFOR in some amitochondriate anaerobic protozoa. PFOR is of particular pharmacological importance because it catalyzes the reductive bio-activation of nitro-based prodrugs to cytotoxic radical metabolites. Metronidazole was developed primarily as an antiprotozoal agent against infections caused by Trichomonas vaginalis. However, its antimicrobial spectrum was subsequently expanded to cover anaerobic bacterial infections. It has been shown that mutations in the genes encoding PFOR result in inherent resistance of PFOR-possessing anaerobic protozoa and bacteria to nitro-based prodrugs. Deciphering the evolutionary history of PFOR is crucial in deepening our understanding of the evolution of anaerobic pathogens and unfold new approaches for drug discovery and targeting in pathogen chemotherapy. Abstract: The present frontrunners in the chemotherapy of infections caused by protozoa are nitro-based prodrugs that are selectively activated by PFOR-mediated redox reactions. This study seeks to analyze the distribution of PFOR in selected protozoa and bacteria by applying comparative bioinformatics approaches to test the hypothesis that PFOR was most likely acquired through horizontal gene transfer (HGT) from bacteria. Furthermore, to identify other genes that were putatively acquired using proteome-wide and gene expression analyses. A plausible explanation for the patchy occurrence of PFOR in protozoa is based on the hypothesis that bacteria are potential sources of genes that enhance optimal adaptation of protozoa in hostile environments. The exclusively expressed proteins obtained from Entamoeba histolytica and the putative gene donor, Desulfovibrio vulgaris, showed an over-expression of eleven genes involved in intermediary metabolism. If these results can be reproduced in other PFOR-possessing protozoa, it would provide a more validated evidence to support the horizontal transfer of pfor from bacteria.

PgRMC1 (progesterone receptor membrane component 1) is a progesterone-binding protein highly expressed in various cancer cells. Its expression has been associated with cancer development, chemoresistance, and poor prognosis in breast cancer through the regulation of drug and sterol metabolism, cell cycle, and apoptosis. However, the precise functions of PgRMC1 remain unclear. We examined PgRMC1 expression in breast cancer tissues and analyzed its correlation with clinicopathological characteristics and treatment response (n=112). PgRMC1 expression was detected in breast cancer tissue, while no immunoreactivity for PgRMC1 was observed in normal breast tissue. Notably, PgRMC1 expression levels were high in the HER2 subtype. Among patients treated with neoadjuvant chemotherapy, those with a poor pathological response had significantly higher PgRMC1 expression than those with a good response. PgRMC1 overexpression in breast cancer cell lines reduced chemosensitivity. Real-time qPCR analyses revealed that PgRMC1 induced the expression of differentiation markers, including CDH1 and KRT19, indicating that PgRMC1 is involved in the suppression of epithelial-mesenchymal transition and mammary luminal epithelial differentiation. Our findings suggest that PgRMC1 may contribute to chemoresistance and serve as a putative biomarker for assessing neoadjuvant chemotherapy sensitivity.

Bovine coronavirus (BCoV) is one of the most common pathogens affecting cattle of all ages. BCoV possesses multiple tissue tropism in cattle, particularly in the respiratory and enteric tracts of the affected animals. Viral entry is a crucial step in the replication cycle of all viruses, including BCoV. The process of viral entry requires the orchestration between several proteins from the virus and the host side. The coronavirus spike glycoproteins contributed substantially to other viral infections and the molecular pathogenesis of coronaviruses, including BCoV. Meanwhile, among all corona-viruses, the hemagglutinin esterase enzyme is found in only BCoV and the human corona-virus-OC43 (HCoV-OC43). The viral receptors are among the key players in the viral entry and could explain the viral tropism, at least in part. The presence of some host cell proteases also en-hances the virus replication from the entry until the release of the virus from the host cells. Previous studies have shown that the 9- O-acetylated sialic acids could potentially act as receptors for the BCoV. However, little is known about the BCoV receptors and if other co/receptors might be needed to ensure viral entry to the host cells. In addition to that, the roles of other host cell proteases, such as Furin and TMPRSS2, in BCoV infection have not yet been well studied. The main objectives of the current study are to identify some novel receptors for BCoV and some host cell proteases that might enhance virus replication. We used some in silico docking tools to predict some new BCoV receptors out of some known other coronavirus receptors (ACE-2, NRP1, DPP4, APN, and CEACAM1). Our results postulated the potential actions of the host Furin and TMPRRS2 enzymes in the activation of BCoV-S glycoprotein, which potentially enhances BCoV replication. Our modeling confirms the high binding affinities of both the 9- O-acetylated sialic and the NRP1 with the BCoV-S and BCoV-HE compared to the ACE-2, DPP4, and CEACAM-1, suggesting their roles as receptors for BCoV. Our prediction models show the potential bindings of the Furin and TMPRSS2 to the BCoV-S polybasic cleavage site (RRSRR|A). To our knowledge, this is the first study to investigate the bovine coronavirus interaction with some other potential host receptors, particularly ACE-2, NRP1, DPP4, APN and CEACAM1, TMPRSS2, and the bovine Furin protease.

In the dynamic arena of healthcare research, where the complexities of data often rival the intricacies of biological systems, the ability to model and analyze such multifaceted datasets is crucial. This comprehensive review delves into the evolution and application of Soft Sets and their extensions, including HyperSoft Sets, SuperHyperSoft Sets, IndetermSoft Sets, IndetermHyperSoft Sets, and TreeSoft Sets, in healthcare claims data analysis. These extensions address intricate challenges in data analysis, offering versatile frameworks for managing uncertainty and indeterminacy inherent in healthcare claims data. By exploring their definitions and applications, this review elucidates how these mathematical tools have evolved and their significance in advancing healthcare research and enhancing data analysis methodologies. Real-world examples underscore the implications of these tools, emphasizing their pivotal role in facilitating informed decision-making and knowledge discovery in healthcare. The review systematically examines various case studies and research findings to illustrate the practical utility of Soft Set extensions. Detailed analyses of real-world scenarios highlight advancements in processing complex healthcare data. The conclusions drawn from this analysis indicate that the adoption of Soft Sets and their extensions can significantly improve the accuracy and efficiency of healthcare data analysis, ultimately contributing to better healthcare outcomes and more informed policy-making. Future research directions are also discussed, suggesting further potential applications and developments in this field.

In this paper the possibility of harvesting energy from the vibrations of a plate is analyzed. The harvester takes the form of a cantilever dynamic vibration absorber equipped with a piezoelectric layer and tuned by means of a tip mass to the first mode of vibration of the plate. A mathematical model of the coupled system composed of the plate and the harvester is presented. The validity of the proposed harvester is proved by means of simulations carried out with the modal expansions approach. Simulation results highlighting the effect of harvester tuning and location are presented as well. Then the validity of the harvester is confirmed by experimental tests carried out both with a concentrated impulsive load and with a distributed pressure load. Simulations and experimental tests show that the cantilever piezoelectric dynamic vibration absorber generates open circuit voltage an order of magnitude larger than the one generated by the same piezoelectric layer when directly bonded to the plate surface.

With the deterioration of the bridge performance and ever-increasing amount of traffic, the bridge safety is becoming a concern for engineering community. A method that can assess the bridge's condition in real-time is urgently needed. The main factors that hinder the bridge condition assessment are the uncertain operational environments. A new moving principal component analysis (MPCA) based method is developed for structural damage detection of bridges in operational environments in this paper. Two main operational environmental factors: the environmental temperature and traffic loads, are studied in the assessment process to verify the robustness and practicality of the proposed method. The numerical and experimental results show that the proposed method is effective and accurate to assess the bridge condition in operational environments.

During the last years the desire and the need for green buildings have been increased. The rise of energy cost, the higher transportation expenses and the international challenges along with the climate change are related with the green buildings market but are also affecting the cost of construction. The aim of this research is to discover and confirm the increased request of green properties and to investigate whether this is related to a new need or just a desire of the buyers. Moreover, the paper examines the people’s knowledge of greenness and sustainability and their wish to live and work in sustainable buildings. Finally, do the buyers will to pay extra in order to purchase a sustainable property and how sustainability can affect the market value and the construction industry. The participants who took part in this research were people that are living and working in Cyprus. One of the significant outcomes was the fact that people who have the knowledge and awareness related to sustainability are willing to pay extra to purchase green properties.

During the last 20 years, with the development of Information and Communication Technologies (ICTs), an emerging interest has appeared in Digital Community Engagement (DCE) in the process of cultural heritage management. Due to a growing need to involve a broader community in the Historic Urban Landscape approach, social media are considered one of the most important platforms to promote the public participation process of urban heritage conservation in the context of rapid urbanization. Despite the growing literature on DCE, which has delivered a general overview of different digital technologies and platforms to enhance heritage conservation, little research has been done on taking stock of the utilization of social media in this process. This study aims to fill the research gap by providing a more comprehensive picture of the functionalities of social media platforms and impacts on sustainable urban development through a systematic literature review. As a result, 19 out of 248 DCE relevant articles are selected as objects to illustrate the contribution of social media. The study identified the characteristics of these applied social media tools, explores their roles and influences in cases. The article concludes with directions for further research.

Sublingual vaccines offer the benefits of inducing mucosal immunity to protect against respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and influenza, while also enabling needle-free self-administration. Previously, we developed a sublingual vaccine formulated with the SARS-CoV-2 receptor binding domain antigen and Poly(I:C) adjuvant in nonhuman primates, cynomolgus macaques. This study examined the immune and inflammatory responses elicited by the sublingual influenza vaccine containing hemagglutinin (HA) antigen and Poly(I:C) adjuvant and assessed the safety of this vaccine in nonhuman primates. The Poly(I:C)-adjuvanted sublingual vaccine induced both mucosal and systemic immunities. Specifically, the sublingual vaccineproduced HA-specific secretory IgA antibodies in saliva and nasal washings, and HA-specific IgA and IgG were detected in the blood. This vaccine appeared to be safe, as judged from the results of blood tests and plasma C-reactive protein levels. Notably, sublingual vaccination neither increased the production of inflammation-associated cytokines—IFN-alpha, IFN-gamma, and IL-17—in the blood, nor upregulated the gene expression of proinflammatory cytokines—IL12A, IL12B, IFNA1, IFNB1, CD69, and granzyme B—in white blood cells. Moreover, DNA microarray analyses revealed that sublingual vaccination evoked both enhancing and suppressing expression changes in genes associated with immune-related responses in cynomolgus monkeys. Therefore, the sublingual vaccine with Poly(I:C) adjuvant is safe and creates a balanced state of enhancing and suppressing the immune-related response.

Silicon Photomultipliers find applications across various fields. One potential Silicon Photomultiplier application domain is neutrino telescopes, where they may enhance the angular resolution. However, the elevated dark count rate associated with Silicon Photomultipliers represents a significant challenge to their widespread utilization. To address this issue, it is proposed to use Silicon Photomultipliers and Photomultiplier Tubes together. The Photomultiplier Tubes signals would serve as a trigger to mitigate the dark count rate, thereby preventing undue saturation of the available bandwidth. This paper presents an investigation into a fast and resource-efficient method for filtering Silicon Photomultiplier dark count rate. A low-resource and fast coincident filter has been developed, which removes the Silicon Photomultiplier dark count rate by using as trigger the Photomultiplier Tube input signals. The architecture of the coincidence filter, together with the first results obtained, which validate the effectiveness of this method are presented.

Keywords: emerging pollutants; pharmaceuticals; plant uptake; soil behavior; soil remediation.

An electrothermal analysis for barium titanate based ceramics is presented combining the Heywang–Jonker model for the electric resistivity with a heat dissipation mechanism based on natural convection and radiation in a one dimensional model on the device level with voltage as the control parameter. Both PTC and NTC effects are accounted for through the double Schottky barriers at the grain boundaries of the material. The problem formulated in this way admits uniform and non–uniform multiple steady state solutions that do not depend on the external circuit. The numerical bifurcation analysis reveals that the PTC effect gives rise to several multiplicites above the Curie point, whereas the NTC effect is responsible for the thermal runaway (temperature blowup). The thermal runaway phenomenon as a potential thermal shock could be among the possible reasons for the observed thermomechanical failures (delamination fracture). The theoretical results for the NTC regime and the thermal runaway are in agreement with experimental flash sintering results obtained for 3% and 8% yttria stabilized zirconia.

Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% of people after the initial SARS-CoV-2 infection, and so far has affected about 65 million people. The etiology of LC remains unclear; however, many pathophysiological pathways may be involved, including viral persistence; chronic, low grade inflammatory response; immune dysregulation and defective immune response; reactivation of latent viruses; autoimmunity; persistent endothelial dysfunction and coagulopathy; gut dysbiosis; hormonal dysregulation, mitochondrial dysfunction; and autonomic nervous system dysfunction. There are no specific tests for the diagnosis of LC, and clinical features including laboratory findings and biomarkers may not specifically relate to LC. Therefore, it is of paramount importance to develop and validate biomarkers that can be employed for the prediction, diagnosis and prognosis of LC and its therapeutic response. Promising candidate biomarkers that are found in some patients are markers of systemic inflammation including acute phase proteins, cytokines and chemokines; biomarkers reflecting SARS-CoV-2 persistence, reactivation of herpesviruses and immune dysregulation; biomarkers of endotheliopathy, coagulation and fibrinolysis; microbiota alterations; diverse proteins and metabolites; hormonal and metabolic biomarkers; as well as cerebrospinal fluid biomarkers. At present, there are only two reviews summarizing relevant biomarkers; however, they do not cover the entire umbrella of current biomarkers or their link to etiopathogenetic mechanisms, and the diagnostic work-up in a comprehensive manner. Herein, we aim to appraise and synopsize the available evidence on the typical laboratory manifestations and candidate biomarkers of LC, their classification based on main LC symptomatology in the frame of the epidemiological and pathogenetic aspects of the syndrome, and furthermore assess limitations and challenges as well as potential implications in candidate therapeutic interventions.

This paper discovers that current variational principle and Noether theorem for different physics systems with (in)finite freedom systems have missed the double extremum processes of the general extremum functional that both is deduced by variational principle and is necessarily taken in deducing all the physics laws, but these have not been corrected for over a century since Noether's proposing her famous theorem, which result in the crisis deducing relevant mathematical laws and all physics laws. This paper discovers there is the hidden logic cycle that one assumes Euler-Lagrange equations, and then he finally deduces Euler-Lagrange equations via the equivalent relation in the whole processes in all relevant current references. This paper corrects the current key mistakes that when physics systems choose the variational extreme values, the appearing processes of the physics systems are real physics processes, otherwise, are virtual processes in all current articles, reviews and (text)books. The real physics should be after choosing the variational extreme values of physics systems, the general extremum functional of the physics systems needs to further choose the minimum absolute extremum zero of the general extremum functional, otherwise, the appearing processes of physics systems are still virtual processes. Using the double extremum processes of the general extremum functionals, the crisis and the hidden logic cycle in current variational principle and current Noether theorem are solved. Furthermore, the new mathematical and physical double extremum processes and their new mathematical pictures and physics for (in)finite freedom systems are discovered. This paper gives both general variational principle and general Noether theorem as well as their classical and quantum new physics, which would rewrite all relevant current different branches of science, as key tools of studying and processing them.

As early as February 2020, many countries have started imposing measures to curb the spread of Covid-19. Despite the right intention, it is a challenging moment for the people, especially the rural population living in the coastal areas. The document presents the preliminary findings on the impacts of Covid-19 on the small scale fisheries in Tun Mustapha Park, Sabah, Malaysia.

Background/Objectives: The management of early breast cancer (BC) includes surgery, followed by adjuvant radiotherapy, chemotherapy, hormone therapy, or immunotherapy. However, the influence of these interventions in metabolic reprogramming remains unknown. This study explored alterations in the plasma metabolome of BC patients following distinct treatments to deepen our understanding of BC pathophysiology, outcomes, and the identification of potential biomarkers. Methods: We included 52 women diagnosed with BC and candidates for surgery as primary oncological treatment. Blood samples were collected at diagnosis, two weeks post-surgery, and one month post-radiotherapy. Plasma samples from 49 healthy women served as controls. Targeted metabolomics assessed 74 metabolites spanning carbohydrates, amino acids, lipids, nucleotide pathways, energy metabolism, and xenobiotic biodegradation. Results: Before treatment, BC patients exhibited notable changes in carbohydrate, nucleotide, lipid, and amino acid metabolism. We noticed a gradual restoration of specific metabolite levels (hypoxanthine, 3-phosphoglyceric acid, xylonic acid, and maltose) throughout different treatments, suggesting a normalization of nucleotide and carbohydrate metabolic pathways. Moreover, we observed increased dodecanoic acid concentrations, a metabolite associated with cancer protection. These variations distinguished patients from controls with high specificity and sensitivity. Conclusion: Oncological treatments modified the metabolism of patients towards a favorable profile with a decrease in the pathways that favor cell proliferation and an increase in the levels of anticancer molecules. These findings emphasize the pivotal role of metabolomics in recognizing the biological pathways influenced by each cancer treatment and the resulting metabolic consequences. Furthermore, it aids in identifying potential biomarkers for disease onset and progression.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with a poor prognosis. Pirfenidone is approved and widely used for the treatment of IPF and reduces lung function decline. The aim of this study was to evaluate the efficacy of different doses of pirfenidone for the prevention of disease progression in patients with IPF. Methods: This was a prospective, observational, single-center cohort study conducted in Haeundae Paik Hospital, Republic of Korea, from April 2021 to March 2023. IPF patients were assigned to three groups according to the dose of pirfenidone (600mg, 1,200mg, 1,800mg). The primary endpoint was the efficacy of pirfenidone according to dose for the prevention of disease progression over 12 months. The secondary endpoint was the role of Krebs von den Lungen-6 (KL-6) in predicting disease progression. Results: A total of 44 patients were enrolled, of whom 39 completed the study, with 13 patients assigned to each of the three groups. The median age was 71.7 years, and 79.5% of patients were men. The baseline characteristics were similar across groups, except the 600mg group was older (75.9 vs. 69.2 vs. 68.2 years, p = 0.016). Fourteen patients (35.9%) suffered disease progression. The rate of disease progression did not differ according to the dose of pirfenidone (38.5 vs. 38.5 vs. 30.8%, p = 1.000). In multivariable logistic regression analysis, KL-6 was not a statistically significant predictor of disease progression. Conclusions: In our study, regardless of dose, consistent pirfenidone use for 12 months resulted in similar efficacy for the prevention of disease progression in patients with IPF. Large-scale, randomized, double-blind, placebo-controlled clinical trials are needed.

18F-fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET-CT) is increasingly used in the diagnosis, prognosis, staging, and treatment monitoring of many tumor types. However, only a small number of studies have reported the use of 18F-FDG PET-CT in intrahepatic cholangiocarcinoma (ICC). This study aimed to examine the accuracy of tumor staging in ICC by using 18F-FDG PET-CT. Between January 2009 and December 2020, patients with suspected ICC were retrospectively enrolled in the study and underwent imaging. The sensitivity and specificity of 18F-FDG PET-CT, CT, and magnetic resonance imaging (MRI) in detecting tumors, satellite focus, vascular invasion, and lymph node metastases were analyzed. The efficacy of 18F-FDG PET-CT for tumor staging was evaluated. Of the 110 patients who were enrolled in the study, 52 underwent surgical treatment and 45 were histologically diagnosed with ICC. When compared with CT or MRI, 18F-FDG PET-CT had similar sensitivity and specificity values for diagnosing satellite focus and vascular and bile duct invasion; however, PET-CT showed higher accuracy in diagnosing regional lymph node metastases. The accuracy of tumor staging by 18F-FDG PET-CT was higher than that by CT/MRI. Thus, 18FDG PET-CT may support tumor staging in ICC.

Objectives: 1) To describe the cardiovascular health of the construction workers in Hong Kong, 2) to examine the demographic differences in cardiovascular health, and 3) to examine the association between modifiable lifestyle behaviors and cardiovascular conditions. Methods: 626 registered construction workers were included in the analysis. Blood chemistry, blood pressure, weight and height were measured. Face-to-face questionnaire interview was conducted. T-tests and One-way ANOVAs were used to compare the cardiovascular health score, cardiovascular outcomes, and lifestyle behaviors by demographic characteristics. Logistic regressions were performed to assess the cardiovascular outcomes by lifestyle behaviors. Results: Two-thirds of the construction workers failed to achieve three out of the seven “ideal” cardiovascular health indicators. The younger, more educated, and female subjects had better cardiovascular health scores than their counterparts. The ideal fish and seafood consumption was associated with 1) ideal weight status and 2) ideal cholesterol level, whereas less soft drink consumption was associated with ideal cholesterol level. Conclusions: The findings highlighted the importance of promoting cardiovascular health in the construction industry. This study provided insights for future interventions, which should include increasing fish and seafood intake, decreasing soft drink consumption, and enhancing the health literacy amongst older, less educated, and male construction workers.

To understand the health impacts of “hikikomori” lifestyle and to establish its first comprehensive health profile, a cross-sectional study was designed to measure how well the cases of hikikomori youths of Hong Kong were living, in terms of social, mental and physical aspects. This study involved 104 eligible participants at age 19.02 year-old who had completed the set of questionnaires and a series of anthropometric and physical health measurements. Despite SF36 score of 84.0 indicated good physical functioning in general, participants were lived sedentarily with high incidence of hypertension at 15.4% and prehypertension at 31.7%. Occurrence of hypertension in cases living as hikikomori >6 months was 3-times higher than those newly onset cases. The blood pressure levels were correlated with age and all obesity index parameters measured including waist circumference and body mass index. Half of the hypertensive cases involved the elevation of systolic blood pressure, which suggested higher odds of cardiovascular complications. Participants were mentally stable living with moderate levels of perceived stress and state anxiety, but borderline clinical depression. In conclusion, the hikikomori lifestyle could be a risk behavior that may harm the younger generation physically by promoting obesity and hypertension and probably other chronic illnesses.

The study focuses on the free vibration analysis of beams made of axially functionally graded materials (AFGM) with curvilinear variable cross-sections along their length. The beams encompass various shapes, including concave and convex conic sections, with axial material properties varying according to polynomial and exponential laws. The equations of motion are derived using Hamilton's principle within the framework of Timoshenko beam theory. These governing equations, subjected to various boundary conditions, are solved using the differential transform method (DTM). The proposed solution technique is validated by comparing computed natural frequencies with existing in literature results and those obtained through three-dimensional finite element analysis in ABAQUS. The incorporation of material gradients into the beam finite element models was achieved through the user-defined material subroutine (UMAT). Additionally, a comprehensive study is conducted to examine the influence of various factors on the natural frequencies of functionally graded beams. These factors include parameters of material laws, types of variable beam shapes, slenderness ratio, and specific boundary conditions. This study provides a thorough understanding of the modal dynamics of the considered beams, offering valuable insights into the behavior of FGM structures.

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

The self-assembly is an intriguing process of great importance in general soft matter and thus re-ceives an ever-growing scientific interest. Its most trivial example is the entropy-driven crystalli-zation of hard spheres. Past works have established the similarities and differences in the phase behavior of monomers and chains made of hard spheres. In the present work, inspired by the dif-ference in the melting points of the pure components, we study, through Monte Carlo simulations, the phase behavior of athermal mixtures composed of fully flexible polymers and individual monomers of uniform size. We analyze how the relative number fraction and the packing density affect crystallization and the established ordered morphologies. A synergetic effect is observed in the crystallization leading to synchronous crystallization of the two species. Structural analysis of the resulting ordered morphologies shows perfect mixing and thus no phase separation, which could split the system into polymer-rich and monomer-rich domains. Due to the constraints imposed by chain connectivity, the local environment of the individual spheres is systematically more spherical and more symmetric compared to the one of spheres belonging to chains. In general, increasing polymer content leads to reduction of the degree of crystallinity. According to the present findings, relative concentration is another determining factor to control the phase behavior of hard colloidal systems based on polymers.

The Tisza River is the longest tributary of the Danube, draining the eastern part of the Carpathian Basin (Central Europe). Five countries share its catchment with different waste production and management practices. Large amounts of waste, including macroplastics (MaPs), are washed into the river. Some of the litter is trapped by the riparian vegetation forming litter accumulations. The study aimed to map the amount of litter by a citizen science program and remote sensing data and to compare the MaP data to the amount of microplastic fragments in sediments. Volunteers reported 3216 riverine litter accumulations from five countries along the entire length of the Tisza (2016–2022). The results suggest that low flow conditions (e.g., impoundment by dams) support litter and MaP trapping. The volume of large accumulations registered by the citizens showed a good correlation with the area of drifting litter revealed on Sentinel-2 images (2015–2021) using machine learning algorithms. Though the MaPs probably fragmentate during their fluvial transport, no clear connection was found between the volume of litter accumulations and the mean microplastic fragment content of sediments (2019–2022). The “Clean Tisza Map“ reveals the high degree of stranded pollutants along rivers and supports public cleanup activities.

Lynch syndrome (LS) is one of the most common hereditary cancer syndrome in human populations, associated with germline variants in MLH1, MSH2/EPCAM, MSH6 and PMS2 genes. The advent of next generation sequencing has proven a significant impact in germline variant detection in the causative genes; however, a large proportion of patients with clinical criteria still receive uncertain or negative results. PMS2 is the least frequent reported gene, associated with up to 15% of LS cases with late-onset disease and low penetrance phenotype; however, the proportion of PMS2-LS cases is considered to be highly underestimated. In this context, we consulted public available databases (ClinVar, LOVD) for missense and intronic PMS2 variants and performed an in silico analysis of the genomic sequence. Splicing bioinformatics tools proven effective in other genes were used to assess both the wild-type DNA sequence and reported genetic variants. Splicing alterations were predicted in silico and using GTEx short-read RNA expression data. Out of the 2384 missense variants discovered, 90% were classified with uncertain significance (VUS). 4.9% of missense variants were shown to have a potential splicing consequence (DS > 0.2) using SpliceAI. As described in the original publication, SpliceAI-visual was proven effective in annotation of short intronic variants (< 50 bp). Four short intronic variants were identified using SpliceAI-visual as potentially splicing disturbing, in spite of using a lower threshold (DS > 0.1). Moreover, we observed that Splicing Regulatory Elements (SREs) may play a fundamental role in alternative splicing in PMS2 gene, ESE motifs being overrepresented in highly expressed exons 5, 11 and 14. Computational analysis performed in our study serves as a valuable filtering step for guiding further RNA sequencing experiments. Additional functional data is necessary to evaluate the significance of our findings.

Utilization of wasted heat instead of fuel combustion is effective to reduce primary energy consumption for mitigating global warming problem. Because wasted heat sources are not necessarily located close to areas of heat demand, one of the difficulties is that wasted heat has to be transferred from heat source side to heat demand side, which may require heat transportation over long distance. From this point we proposed and have examined new idea of heat transportation using ammonia-water as the working fluid which system is named Solution Transportation Absorption chiller, in short STA. Our previous studies of STA were mainly the experimental investigation with STA facility which cooling power was 25RT (90kW). As a result, the COP of STA was found almost same value 0.65 with the conventional absorption chiller without depending on the transportation distances. The simulation using AspenHYSYS also examined with same experimental condition. The experimental data showed good agreement with the simulation calculation. In this study, we examined the large-scale cooling power STA on simulation. The examination cooling powers were from 90 kW(25RT) to 3517 kW(1000RT). All cooling power achieved around COP 0.64 including pump power consumptions. In addition, we performed the dynamic simulation. As the results, there was no effect of pipeline size on the cooling capacities and mass flow rates. Furthermore, the stability time of the cooling capacities and mass flow rates were almost same regardless of the pipeline size and cooling capacity. In other words, STA may be achieved the same COP even though having various complex conditions compared with the conventional absorption chiller.

Rosemary is one of the most important medicinal plants for natural therapy due to its multiple pharmacological properties, such as antioxidant, anti-inflammatory, neuroprotective, antiproliferative, antitumor, hepato- and nephroprotective, hypolipidemic, hypocholesterolemic, antihypertensive, anti-ischemic, hypoglycemic, radioprotective, antimicrobial, antiviral, antiallergic, wound healing. Our study reports for the first time, over a 12-month period, the identification and quantification of polyphenols and the investigation of the antioxidant and acetylcholinesterase (AChE) inhibitory activity of the Rosmarinus officinalis L. species harvested at flowering from the flora of southwestern Romania (Oltenia Region). Identification and quantification of polyphenolic acids was made by ultra-high-performance liquid chromatography/mass spectrometry (UHPLC/MS). Total phenolic content was determined using the spectrophotometric method. In situ antioxidant and anticholinesterase activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and AChE inhibitory assay, respectively, on high-performance thin-layer chromatography (HPTLC) plates. DPPH radical scavenging activity was also assessed spectrophotometrically. The results revealed significant correlations between specific polyphenolic compounds and the measured biological activities, understanding the role of seasonal variations and providing insights into the optimal harvesting times and medicinal benefits of rosemary. Our research brings new information on the phytochemical profile of R. officinalis, as a natural source of polyphenols with antioxidant and AChE inhibitory properties.

An emerging picture in cancer biology is that, paradoxically, chemotherapy can actively induce changes that favor cancer progression. These pro-cancer changes can be either inside (intrinsic) or outside (extrinsic) the cancer cells. In this review, we will discuss the extrinsic pro-cancer effect of chemotherapy; that is, the effect of chemotherapy on the non-cancer host cells to promote cancer progression. We will focus on metastasis, and will first discuss recent data from mouse models of breast cancer. Intriguingly, despite reducing the size of primary tumors, chemotherapy changes the tumor microenvironment, resulting in an increased escape of cancer cells into the blood stream. Furthermore, chemotherapry changes the tissue microenvironment at the distant sites, making it more hospitable to cancer cells upon their arrival. We will then discuss the idea and evidence that these devastating pro-metastatic effects of chemotherapy can be explained in the context of stress response. At the end, we will discuss the potential relevance of these mouse data to human breast cancer and their implication on chemotherapy in the clinic.

Coronavirus disease 2019 (COVID-19) has affected medical practice. More than 7,000,000 patients died worldwide after being infected with COVID-19; however, no specific laboratory markers have yet been established to predict death related to this disease. In contrast, electrocardiographic changes owing to COVID-19 include QT prolongation and ST-T changes; however, there have been no studies on ambulatory electrocardiographic markers of COVID-19. We encountered three patients diagnosed as having COVID-19 who did not have a prior history of significant structural heart diseases. All had abnormalities in ambulatory echocardiogram parameters detected by high-resolution 24-h electrocardiogram monitoring: positive late potentials (LPs) and T-wave alternans (TWA), abnormal heart rate variability (HRV), and heart rate turbulence (HRT). Case 1 involved a 78-year-old woman with a history of chronic kidney disease, Case 2 a 76-year-old man with hypertension and diabetes, and Case 3 a 67-year-old man with renal cancer, lung cancer, and diabetes. None of them had a prior history of significant structural heart disease. Although no significant consistent increases in clinical markers were observed, all three patients died, mainly because of respiratory failure with mild heart failure. LP, TWA, HRV, and HRT were all positive in three cases with no significant structural cardiac disease at the initial phase of admission. There is a possibility that LP, TWA, HRV, and HRT have the potential to be risk stratifiers of COVID-19 pneumonia in the early phase of admission. Further accumulation of data regarding ambulatory electrocardiographic markers in patients with COVID-19 is needed.

Background: Positive person-centered attributes of inpatient rehabilitation need to be identified from the patient perspective to be further developed and sustained. Purpose: To identify which attributes patients openly evoke as being great care experiences, using an open appreciative inquiry during the inpatient rehabilitation stay. Methods: Qualitative secondary analysis of appreciative patient comments during a bedside patient experience rounding, facilitated by a neutral party. Two independent analysts employed an inductive, summative form of content analysis. Results: Among 150 patients rounded, 122 provided categorizable appreciative accounts. Over two thirds of the patients (67.2%) focused on “staff attributes” in their great-experience accounts. Those attributes were mostly interpersonal such as being “attentive & caring - beyond clinical duty” and being “encouraging (but not too hard) & reassuring”. These interpersonal staff attributes were reported with words showing deep levels of personal significance or patient appreciation. Beyond staff attributes, the perceived quality of the “patient care” (31.1%) and opportunities for “leisure and social activities” (9.0%) were also frequently evoked. Amenities like food or costumer service were the least evoked, rarely so as an exclusive attribute (0.8% for each). Conclusions: The human(e) factor, especially the interpersonal qualities of staff, emerged as greatly appreciated from the patient experience perspective during inpatient rehabilitation. These experiences help identify which person-centered attributes of care might be further developed and sustained.

Hip replacement has significantly improved the quality of life of patients with symptomatic hip osteoarthritis. Metal-on-metal (MoM) bearings have been used with conventional total hip re-placement (THR) for several decades with promising results from early applications. Wear and corrosion of these implants may lead to a release of metal products into surrounding tissue and body fluids. From the 1980s onwards, the search for increasingly better coupling materials with low levels of wear led to the rise of hard-on-hard couplings such as ceramic-on-ceramic (CoC). The latter is currently the coupling with the longest known duration and with a wear rate close to zero. MoM coupling has been for a long time the most significative alternative, but systemic and local complications linked to the release of chromium and cobalt ions, determine the withdrawn from the market. One other alternative proposed over the time has been Ceramic-on-Metal (CoM) bearing. Preliminary results have been described as favourable, but due to the failures of metal on metal it has been withdrawn from the market, without causing significant clinical complications. In this narrative review, we analysed risks and benefits associated with the implantation of hybrid hard-on-hard bearings, such as CoM.

Salivarian trypanosomes are extracellular parasites causing anthroponotic and zoonotic infections. Anti-parasite vaccination in considered the only sustainable method for global trypanosomosis control. Unfortunately, not a single field applicable vaccine solution has been successful so far. Active destruction of the host’s adaptive immune system by trypanosomes is believed to contribute to this problem. Here we show Trypanosome brucei brucei infection results in the lasting obliteration of immunological memory, including vaccine-induced memory against non-related pathogens. Using the well-established DTPa vaccine model in combination with a T. b. brucei infection and diminazene diaceturate anti-parasite treatment scheme, our result demonstrate that while the latter ensured the full recovery from the T. b. brucei infection, it failed to restore an efficacious anti-pertussis vaccine recall response. DTPa vaccine failure coincided with a shift in the IgG1/IgG2a anti-pertussis antibody ratio in favor of the latter, and a striking impact on all spleen immune cell populations. Interestingly, an increased plasma IFNy level in DTPa vaccinated trypanosome infected mice did result in a temporary antibody-independent improvement of early-stage trypanosomosis control. In conclusion, our results are the first to show that trypanosome inflicted immune damage is permanent, and is not restored by successful anti-parasite treatment.

Standardized protocols were specifically designed and developed for clinical information collection and obtaining trio genomic information from infants affected with congenital anomalies (CA) and their parents, as well as securing human biological resources. Two large areas of these protocols include clinical and genomic information collection on CA which were difficult to diagnose using pre-existing screening methods. The following are three essential items for the clinical information collection protocol: establishment of a consent system for collecting and utilizing research resources, establishment of criteria for target patient selection, and collection of clinical and epidemiological information. A total of 138 cases consisting of 45 families of infants with CA and their parent trios have provided human-derived resources and genomic information. Whole genome sequencing data have been generated for all participants, and standardized protocols for resource collection and manufacturing have been developed. Phenotype information according to the Human Phenotype Ontology term and major test findings were recorded. It is important to keep updating and recording clinical symptoms and genetic diagnosis that are newly added or changed over time. The unique significance of this study is to develop a protocol that enables long-term tracking by adding growth and development tests that reflect important characteristics of newborns. By using these clinical and genetic information collection protocols for CA, it will be possible to establish an essential platform for early genetic diagnosis and diagnostic research, and further present new genetic diagnostic guidelines in the near future.

Background: Malnutrition in critically ill paitents is closely linked with clinical outcomes. During acute inflammatory states, nutrition cannot reverse the loss of body cell mass completely. Studies on nutritional screening and strategy considering metabolic changes not yet been conducted. We aimed to identify nutrition strategies using the modified Nutrition Risk in the Critically ill (mNUTIRC) score. Methods: Nutrition support data, laboratory nutrition indicators, and prognosis indices were prospectively collected on the 2nd and 7th day after admission. It is to identify the effect of changes on the metabolic status and critical target of nutrition intervention. To discriminate the high-risk group of malnutrition, receiver operating characteristic curves were plotted. Risk factors associated with 28 day-mortality were evaluated using multivariable Cox proportional hazards regression. Results: A total of 490 and 266 patients were analyzed on the 2nd and 7th day, respectively. Only the mNUTRIC score showed significant differences in nutritional risk stratification. The use of vasopressors, hypo-protein supply (< 1.0 g/kg/day), high mNUTRIC score and hypoalbuminemia (<2.5 mg/dl) in the recovery phase was strongly associated with 28-day mortality. Conclusions: The implementation of the mNUTRIC score and protein supply in the post-acute phase is critical to improve 28-day mortality in critically ill patients.

The paper provides and comments on the results of studies of the effect of sandstone-based abrasives and quartz sand alone on the wear of martensitic surfaces of wear-resistant steels. The wear process was examined on a ring-on-ring test rig seeking to determine the mass decrement parameter which characterised wear. The tests were conducted for three sandstone varieties: Carboniferous, Permian, and Cretaceous, and they made it possible to determine that the most intense process of deterioration of wear-resistant steels took place in the presence of quartz sand grain, while less intense wear was observed in the case of sandstone-based abrasives. The mass decrement values established in the presence of the sandstones in question did not differ significantly between individual sandstone varieties. Based on a surface damage analysis, the basic damage mechanism was found to be micro-scratching, however, with regard to the sandstones examined, it was also determined that individual grains could be pressed into surface irregularities, as well as that films of soft hematite cement developed in the Permian sandstone and that inclusions of carbonaceous matter were formed in the Carboniferous sandstone. With reference to the wear process observations, a wear model was described for the surface of the steels examined in the presence of sandstone-based abrasives.

The agricultural sector is amidst an industrial revolution driven by the integration of sensing, communication, and artificial intelligence (AI). Within this context, the internet of things (IoT) takes center stage, particularly in facilitating remote livestock monitoring. Challenges persist, particularly in effective field communication, adequate coverage, and long-range data transmission. This study focuses on employing LoRa communication for livestock monitoring in mountainous pastures in the north-western Alps in Italy. The empirical assessment tackles the complexity of predicting LoRa path loss attributed to diverse land-cover types, highlighting the subtle difficulty of gateway deployment to ensure reliable coverage in real-world scenarios. Moreover, the high expense of densely deploying end devices makes it difficult to fully analyze LoRa link behavior, hindering a complete understanding of networking coverage in mountainous environments. This study aims to elucidate the stability of Lora link performance in spatial dimensions and ascertain theextent of reliable communication coverage achievable by gateways in mountainous environments. Additionally an innovative deep learning approach was proposed to accurately estimate path loss across challenging terrains. Remote sensing contributes to land-cover recognition, while Bidirectional Long Short-Term Memory (Bi-LSTM) enhances the path loss model’s precision. Through rigorous implementation and comprehensive evaluation using collected experimental data, this deep learning approach significantly curtails estimation errors, outperforming established models. Our results demonstrate that our prediction model outperforms established models with a reduction in estimation error to less than 5dB, marking a 2X improvement over state-of-the-art models. Overall, this study signifies a substantial advancement in IoT-driven livestock monitoring, presenting robust communication and precise path loss prediction in rugged landscapes.

Synaptopodin 2-like protein (SYNPO2L) is localized in the sarcomere of cardiomyocytes and is involved in heart morphogenesis. However, the molecular function of SYNPO2L in the heart is not fully understood. We investigated the interaction of SYNPO2L with sarcomeric alpha-actinin and actin filaments in cultured mouse cardiomyocytes. Immunofluorescence studies showed that SYNPO2L colocalized with alpha-actinin and actin filaments at the Z-discs of the sarcomere. Recombinant SYNPO2La or SYNPO2Lb caused bundling of actin filaments in the absence of alpha-actinin and enhanced alpha-actinin-dependent formation of actin bundles. In addition, high-speed atomic force microscopy revealed that SYNPO2La directly bound to alpha-actinin via its globular ends. The interaction between alpha-actinin and SYNPO2La stabilized the two proteins on actin filaments. These results strongly suggest that SYNPO2L cooperates with alpha-actinin during actin bundle formation to facilitate sarcomere formation and maintenance.

We used numerical methods to define the normative structure of the different stages of sleep and wake (W) in a pilot study of 19 subjects without pathology (18–64 years old) using a double-banana bipolar montage. Artefact-free 120–240 s epoch lengths were visually identified and divided into 1 s windows with a 10% overlap. Differential channels were grouped into frontal, parieto-occipital, and temporal lobes. For every channel, the power spectrum (PS) was calculated via fast Fourier transform and used to compute the areas for the delta (0–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), and beta (13–30 Hz) bands, which were log-transformed. Furthermore, Pearson’s correlation coefficient and coherence by bands were computed. Differences in logPS and synchronization from the whole scalp were observed between the sexes for specific stages. However, these differences vanished when specific lobes were considered. Considering the location and stages, the logPS and synchronization vary highly and specifically in a complex manner. Furthermore, the average spectra for every channel and stage were very well defined, with phase-specific features (e.g., the sigma band during N2 and N3, or the occipital alpha component during wakefulness), although the slow alpha component (8.0–8.5 Hz) persisted during NREM and REM sleep. The average spectra were symmetric between hemispheres. The properties of K-complexes and the sigma band (mainly due to sleep spindles – SSs) were deeply analysed during the NREM N2 stage. The properties of the sigma band are directly related to the density of SSs. The average frequency of SSs in the frontal lobe was lower than that in the occipital lobe. In approximately 30% of patients, SSs showed bimodal components in anterior regions. qEEG can be easily and reliably used to study sleep in healthy subjects and patients.

In an era marked by swift technological progress, the pivotal role of Artificial Intelligence (AI) is increasingly evident across various sectors, including local governments. These governmental bodies are progressively leveraging AI technologies to enhance service delivery to their communities, ranging from simple task automation to more complicated engineering endeavours. While more and more local governments are adopting AI, it is imperative to understand the functions, implications, and consequences of AI. Despite the growing importance of this domain, a significant gap persists within the scholarly discourse. This study strives to bridge this void by exploring the applications of AI technologies within the context of local government service provision and using this inquiry to generate lessons and best practices for similar smart city initiatives. Through a comprehensive grey literature review, we analysed 262 real-world AI implementations across 170 local governments worldwide. The findings underscore several key points: (a) There has been a consistent upward trajectory in the adoption of AI by local governments over the last decade; (b) Local governments from China, the US, and the UK are at the forefront of AI adoption; (c) Among local government AI technologies, Natural Language Processing and Robotic Process Automation emerge as the most prevalent ones; (d) Local governments primarily deploy AI across 28 distinct services; (e) Information management, back-office work, and transportation and traffic management are leading domains in terms of AI adoption. This study enriches the extant body of knowledge by providing an overview of existing AI applications within the sphere of local governance. It offers insights for smart city policymakers and decision-makers considering the adoption, expansion, or refinement of AI technologies in urban service provision. Additionally, it underscores the importance of using these insights to guide the successful integration and optimisation of AI in future smart city projects, ensuring they meet the evolving needs of communities.

Objectives: The study aimed to develop a deep learning-based edge AI model deployed on electrocardiograph (ECG) devices for real-time detection of atrial fibrillation (AF)-risk during sinus rhythm (SR) using standard 10-second 12-lead electrocardiograms (ECGs). Methods: A novel approach was used to convert standard 12-lead ECGs into binary images for model input, and a lightweight convolutional neural network (CNN)-based model was trained using data collected by the Japan Agency for Medical and Research Development (AMED) between 2019 and 2022. Patients over 40 years old with digital, SR ECGs were retrospectively enrolled and divided into AF and non-AF groups. Data labeling was supervised by cardiologists. The dataset was randomly allocated into training, validation, and internal testing datasets. External testing was conducted on data collected from other hospitals.　Results: The best-trained model achieved an AUC of 0.82 and 0.80, sensitivity of 79.5% and 72.3%, specificity of 77.8% and 77.7%, precision of 78.2% and 76.4%, and overall accuracy of 78.6% and 75.0% in the internal and external testing datasets, respectively. The deployed model and app package utilized 2.5MB and 40MB of the available ROM and RAM capacity on the edge ECG device, correspondingly. Processing time for AF-risk detection was approximately 2 seconds.　Conclusion: The model maintains comparable performance and improves its suitability for deployment on resource-constrained ECG devices, thereby expanding its potential impact to a wide range of healthcare settings. Its successful deployment enables real-time AF-risk detection during SR, allowing for timely intervention to prevent AF-related serious consequences like stroke and premature death.

This study aimed to investigate the fatigue performance and interfacial strengthening mechanisms of Al6061-to-Cu dissimilar lap joints via electromagnetic pulse welding (EMPW). The load-bearing capacity of the joints at discharge voltages of 14 kV and 16 kV was superior to that of 12 kV. Furthermore, the fatigue life of the 14 kV joints was one order of magnitude higher compared to the 12 kV joints. SEM observation of the fatigue fracture surface revealed the presence of typical "tire-mark" fatigue striations only in the 14 kV joint, indicating higher ductility and the ability to withstand extended plastic deformation. Notably, ultra-fine nanocrystalline Al2Cu phase, amorphous phase, and numerous dislocations hindered EBSD acquisition in the transition zone. Nevertheless, dense low-angle grain boundaries (LAGBs) and refined grains were examined at the bonding interface. This suggests that the high-velocity collision caused severe plastic deformation and led to the formation of substructures. The interfacial strength was attributed not only to the "wave-like" or "inverted hook-like" diffusion layer but also to the presence of refined grains along the interface and nanocrystalline Al2Cu in the transition zone. Furthermore, the hybrid nanocrystalline-amorphous microstructure strengthened the joint by regulating the balance between strength and ductility.

(1) Background: This study aimed to evaluate whether the implementation of a modified blood sampling protocol, which focused on need-based laboratory testing and minimized venous sampling by replacing it with point-of-care testing (POCT) via capillary puncture, successfully reduced iatrogenic blood loss, incidence of anemia, and frequency of blood transfusion in extremely low birth weight infants (ELBWIs) without negatively affecting neonatal outcomes. (2) Methods: A retrospective analysis was conducted on 313 ELBWIs of gestational age (GA) between 23 and 28 weeks, born between 2013 and 2019. The infants were divided into two groups: before (period I) and after (period II) the implementation of the modified blood sampling protocol in January 2016. Propensity score matching was conducted to minimize selection bias. Clinical data, including the frequency and amount of blood sampling, frequency and volume of blood transfusion, and clinical characteristics, such as gestational age, birth weight, and neonatal outcome data, were collected and compared between the two groups. (3) Results: No significant differences in the GA or birth weight between the two periods were observed. The total sampling volume during a month after birth (16.7 ± 4.1 mL vs. 15.6 ± 4.4 mL, P=0.03) and total sampling volume during hospital days (51.4 ± 29.7 mL vs. 44.3 ± 27.5 mL, P=0.04) in period II were significantly lower than that in period I. There were no differences in the mortality or morbidity between the two periods. Although the transfusion frequency and amount did not have significant differences between the periods, we observed a positive correlation between the transfusion frequency and sampling volume (coefficient: 0.09, 95% CI: 0.08–0.11). (4) Conclusions: The modified blood sampling protocol effectively reduced the iatrogenic blood loss without negatively affecting the neonatal outcomes.

Typhonium flagelliforme is an Indonesian herbal plant used and applied traditionally to treat cancer diseases. Gamma rays have irradiated rodent tuber mutant plant at six doses gray to in-crease the chemical compounds of anticancer activity. The effect of isolated compounds from ro-dent tuber mutant plants has never been studied and published yet. Our study unveiled the poten-tial of stigmasterol as a remarkable cytotoxic agent and the significant contribution of NMR spectroscopy, IR, Mass spectra, QTOF MS towards the isolation and identification of this anti-cancer agent. Stigmasterol was isolated from T. flagelliforme mutant plant. Stigmasterol was more effective against MCF-7 cells with an IC50 value of 0.1623 µM than Cisplatin with IC50 value 13.2 µM. It is the most potential and active fraction in the human breast cancer cell line. The mo-lecular docking study analyzed the chemical profile of stigmasterol to confirm the receptor in agonist binding sites. The prediction of the toxicity of stigmasterol compounds using in silico and analysis of its interaction with the receptor can act as a competitive regulator with a high-affinity binding site on FXR. Stigmasterol has potential as a candidate for an anticancer drug that pro-moting further clinical action.

It has been regarded that Vibrio cholerae O1 inhabit in environmental water. As many cholera patients emerge in Kolkata, it has been thought that V. cholerae O1 is easily detected in environmental water in Kolkata. However, the detection of V. cholerae O1 is rare, though other V. cholerae (NAG Vibrio) is constantly detected. To clear the reason for the difference of the detection rate of two Vibrios, we examined the viability of V. cholera O1 and NAG Vibrios in low ionic strength aquatic medium. We observed greater declining viability of V. cholerae O1 possessing cholera toxin gene (ctx) in low ionic strength solution, but the decline of NAG Vibrios non-possessing ctx is small. To evaluate the concerning of ctx in the viability, we examined the viabilities of V. cholerae O1which do not possess ctx and NAG Vibrios possessing ctx under the same condition. The result indicated that the existence of the ctx induces the decrease the viability of the host in low ionic strength solution. The decrease observed in this experiment might relate with the low detection of V. cholerae O1 possessing ctx in environmental water, though NAG Vibrio is constantly detected.

Extremely low-frequency electromagnetic fields (ELF-EMFs) are non-ionizing radiations typically emitted by power lines, electrical wiring and electrical appliances. Epidemiological studies have repeatedly shown a positive association between ELF-EMFs and childhood leukemia. Exposures greater than 0.3-0.4 µT increase the risk by approximately 1.5-2 fold, and estimates indicate that up to 2% of childhood leukemia cases in Europe may be attributable to ELF-EMFs. However, it is considered unlikely that ELF-EMFs can cause cancer, because carcinogenesis requires the accumulation of DNA alterations and ELF-EMFs do not have enough energy to damage the DNA. Lack of biological plausibility is a barrier to accept the evidence of carcinogenicity in human studies and to take measures to protect pregnant women and children from ELF-EMFs. Recent evidence indicates that non-mutagenic agents can cause DNA alterations and increase the risk of cancer by promoting the accumulation of cell divisions in stem cells. Cell division generates DNA alterations (e.g., mutations arising during DNA replication), which occur even in the absence of DNA-damaging agents. Importantly, ELF-EMFs can trigger the division of stem cells; this effect is under development in the field of regenerative medicine. A possible mechanism by which ELF-EMFs induce the malignant transformation of hematopoietic stem cells is discussed.

Epidemiological data indicate that 5.8% of cancer deaths world-wide are attributable to alcohol consumption. The risk of cancer is higher in tissues in closest contact on ingestion of alcohol, such as the oral cavity, pharynx and esophagus. The risk of these cancers is increased even in people who have only one alcoholic drink per day. However, since ethanol is not mutagenic and the carcinogenic metabolite of ethanol (acetaldehyde) is mostly produced in the liver, it is not clear why alcohol use preferentially exerts a local carcinogenic effect. It is well known that ethanol causes cell death at the concentrations present in alcoholic beverages; however, this effect has been overlooked probably because dead cells cannot give rise to cancer. Here I discuss that the cytotoxic effect of ethanol on the cells lining the oral cavity, pharynx and esophagus activates the division of the stem cells located in deeper layers of the mucosa to replace the dead cells. Every time stem cells divide, they become exposed to unavoidable errors associated with cell division (e.g., mutations arising during DNA replication and chromosomal alterations occurring during mitosis) and also become highly vulnerable to the genotoxic activity of endogenous and exogenous DNA-damaging agents (e.g., reactive oxygen species, acetaldehyde and tobacco carcinogens). Alcohol consumption probably increases the risk of developing cancer of the oral cavity, pharynx and esophagus by promoting the accumulation of cell divisions in the stem cells that maintain these tissues in homeostasis. Because the cytotoxic activity of ethanol is concentration-dependent, the risk of these cancers will not only increase with increasing amounts of ethanol, but also with increasing concentrations; an ounce of whisky is probably more carcinogenic when taken undiluted than when taken mixed with non-alcoholic beverages. The local cytotoxic effect of ethanol can also explain the known synergistic effect of alcohol and tobacco use on the risk of these cancers. Understanding the mechanisms of carcinogenicity of alcohol is important to reinforce the epidemiological evidence and to raise public awareness of the strong link between alcohol consumption and cancer.

Tobacco use, most people would say. Smoking tobacco increases the risk of developing many types of cancer and is responsible for approximately one-third of all cancer deaths. The association between tobacco use and lung cancer is well known; lung cancer occurs about 20 times more often in heavy smokers than in nonsmokers [1]. However, many lung cancers are diagnosed in never smokers [2], and most smokers do not develop lung cancer [3,4].

Super duplex stainless steel (SDSS) is used for manufacturing large valves and pipes in offshore plants because of its excellent strength and corrosion resistance. Large valves and pipes are manufactured by forging after casting, and the outside and inside microstructures are different owing to the difference in the cooling rate caused by the thermal conductivity. This microstructural variation causes cracks during solution annealing, which breaks the materials. To study toe corrosion resistance of the SDSS forged material, the microstructure was conducted based on the difference in the cooling rate between the inside and outside of the cast SDSS. To analyze the effects of the secondary phase fraction before solution annealing on the solution and corrosion resistance, the corrosion resistance with and without solution annealing was measured using the potentiodynamic polarization test and critical temperature test after the precipitation of the secondary phase. In the potentiodynamic polarization test, the secondary phase decreased the activation polarization and increased the corrosion rate. The critical pitting temperature exhibited the effect of the secondary phase.

As an export commodity coffee industry contributes to the economies of both exporting and importing countries. The aim of the study involves competitiveness and determinant of coffee export in Ethiopia through the period of 1990–2018 observations. To explain the level of comparative advantage and competitiveness respectively Revealed Comparative Advantage and Syematric Revealed Comparative Advantage were employed. To capture determinans of coffee ARDL model with bound testing to co-integration approach was employed to investigate the long-run association between Ethiopian total coffee export in bags (60kg each) with domestic coffee production, world coffee price, real exchange rate, FDI, world coffee production and price ratio. Even though Ethiopia has the comparative advantage in the export of coffee, however, the share it in the international market low in amount and not inlined with RCA. Bound testing to co-integration approach result confirmed the existence of a long-run relationship between total coffee exports of Ethiopia with its independent variables. The analysis pointed out that in the long run the extent of domestic coffee production, world price, and real exchange rate positively and significantly affects total coffee export. However, FDI, price ratio, world production of coffee have negative & significant effects. In the short-run Ethiopian total coffee export defined as a positive significant function of domestic coffee production and real exchange rate positive but insignificant effect with Level of RCA and world price as well as a negative function of FDI, price ratio, and world production of coffee. Coefficient Error Correction Model (ECM (-1)) was negative and significant with a value of 134.4 % of the adjustment would make each year and return to its long-run equilibrium after 1.3 years. The policy implication calls for addressing issues of the combined effect of the policy setting, institutions, and market failures to avoid the evil effect of the sector.

The origin of a product, consumer familiarity, and purchasing identity are factors that affect perception of cheese consumption. The present study aims at identifying consumers’ conceptualizations and attitudes towards local Greek cheeses of the North-Aegean Sea islands, such as Ladotyri, Graviera, Kasseri, Kaskavali, Melichloro, and Kalathaki, some of which have a Protected Designation of Origin (PDO) status, as opposed to cheeses of non-Greek origin, such as Cheddar, Regatto, and Gouda. Sensory and emotional attributes of local, local PDO, and imported cheeses, and drivers associated with consumers’ choice and acceptance above and beyond their sensory attributes were studied, using three methods: a) Flash Profile to gain insight into the sensory positioning of products and description of samples, b) qualitative analysis of focus groups to pinpoint consumer knowledge, preference, and consumption criteria, and c) a new methodology for natural language processing and sentiment analysis of social media posts to determine consumer conceptualizations. Social media posts have proven to be a valuable source of linguistic and cultural data for cheeses. Local cheeses, including PDO products, were found to be linked to village life and family gatherings, home, tradition, and childhood memories, with saltiness and hardness being their main sensory attributes. Imported cheeses were linked to fast food, pizza, and snacking, with elasticity and gumminess as prominent sensory qualities. The main criterion of purchase was intended usage and versatility, taste and texture, price, and familiarity. The findings provide key sensory attributes, information about consumer purchasing criteria, and relevant vocabulary for the promotion of cheeses as agri-food and gastronomic identity key products.

Background: Atopic dermatitis is a chronic condition that significantly affects the daily life of those who suffer from it, requiring complex and personalized management with active participation of the patient in the management of their disease. Objective: to describe the design and development process of a mobile application, using the Design Thinking method, for the follow-up of patients with atopic dermatitis. Methods: User-centered design and prototype creation method, differentiating the phases of the empathize, define, idea, prototype, and test. A purposive snowball sampling was used to recruit patients with atopic dermatitis, family members, and health professionals. Three two-hour workshops were held, attended by 25 people. Results: the parameters to be monitored will include objective data (physical, behavioral, treatments, environmental, integration of daily routines) and subjective data (user experience). On the other hand, it will figure out behavior patterns, set up rewards, foster a feeling of community, and use notifications and a chatbot. Conclusion: The active integration of all stakeholders at each stage of the design and development of the digital solution has improved its relevance and acceptance, resulting in a tool that is expected to significantly improve the management of atopic dermatitis.

General derivation of the well-known Ren-Otsuka relation, 1/α (dTo)/dx=-α/β (where To, x, α and β(>0) are the transformation temperature, the composition, as well as the composition and temperature coefficient of the critical shear constant, c’, respectively) for shape memory alloys, SMAs, is provided based on the similarity of interatomic potentials in the framework of dimensional analysis. A new dimensionless variable, to(x)=(To (x))/(Tm (x) ), describing the phonon softening (where Tm is the melting point) is introduced. The dimensionless values of the heat of transformation, H, and entropy, S as well as the elastic constants c’, c44, A=c44/c' are universal functions of to(x) and have the same constant values at to(0) within sub-classes of host SMAs having the same type of crystal symmetry change during martensitic transformation. The ratio of (dto)/dx and α has the same constant value for all members of a given sub-class and relative increase of c’ with increasing composition should be compensated by the same decrease of to. In the generalized Ren-Otsuka relation the anisotropy factor, A appears instead of c’ and α as well as β are the differences of the corresponding coefficients for the c44 and c’ elastic constants. The obtained linear relation between h and to rationalizes the observed empirical linear relations between the heat of transformation measured by DSC (QAM) and the martensite start temperature, Ms.

The energy efficiency of existing buildings is a crucial factor in addressing Europe’s energy con-sumption challenges, accounting for nearly 40% of the total energy usage. The ongoing energy crisis, driven by the reliance on fossil fuels and increasing prices, has underscored the urgency of adopting sustainable and energy efficient practices especially to the existing building stock. Cyprus is par-ticularly vulnerable due to its heavy dependence on imported fuels for electricity generation and faces significant challenges in transforming its existing building stock into energy-efficient and sustainable structures. Extensive focus has been made by the government on the energy-efficient retrofit of non-residential public buildings. This study examines an existing cultural hall. The case study of the Cultural Hall represents the building stock before 2010 which is lacking thermal in-sulation, double glazing and any energy efficient element. It then offers an ideal case study to ex-plore sustainable solutions which can be easily adopted from the construction industry and from the building owners. The primary objective of this research is twofold: first, to develop a comprehensive retrofit plan to transform the cultural hall into a net-zero energy building; and second, to explore how this transformation can give value back to the local community. After running two simulation scenarios and providing two energy performance certificates, one with at the existing state and one with the intended retrofit measures, it is clear that the building can be a net zero energy consump-tion building. Some interesting results derived, present also how this building can provide value back to the community i.e. through solar carports for EV charging.

Computational methods are essential to support and advance nuclear technologies due to the hazards of handling and analysing highly radioactive materials such as spent nuclear fuel (SNF). However, many such methods, including those thatcan predict SNF compositions and decay heat parameters, require expensive, proprietary software, alongside significant programming experience and computational power for utilisation, severely limiting availability of data and hampering research throughput. Although some datasets are available, many are incomplete or only cover certain fuel systems for older reactor types. Research investigating new methods for SNF recycling, for example, requires compositional and decay heat data for fuel systems not covered by extant data, though analogous source data may be available. With this in mind, we have developed a simple, accessible, and flexible method for extrapolation of isotopic, elemental, and decayheat compositions for SNF at discharge and following decay storage before recycling, based on an extant dataset. This semi-empirical method uses physical and mathematical first principles and can be performed using software accessible to all researchers. This provides outputs accurate to within 1% of reference values interpolated within the range of available data for isotopic compositions, with sensible extrapolations at higher burnups beyond those reported, withoverall elemental outputs accurate to within 0.1%of expected totals. In this publication, we present the developmental methodology, some sample data, the present limitations, and options for future development and expansion of functionality.

Abstract: Given the links between parental obesity and eating psychopathology in their children, it is important to understand the mechanisms via which unhealthy relationships with eating are passed from parents to children. The aim was to review research focusing on food-related parenting practices (FPPs) used by parents with overweight/obesity. Web of Science, PubMed and PsycINFO were searched. Twenty studies were included in the review. Single studies suggest differences between parents with healthy-weight vs overweight/obesity with respect to; food accessibility, food availability and modelling. Multiple studies suggest that several parenting strategies do not differ according to parental weight status (child involvement, praise, use of food to control negative emotions, use of food-based threats and bribes, pressure, restriction, meal and snack routines, monitoring, and rules and limits). There was inconclusive evidence with respect to differences in parental control, encouragement and use of unstructured FPPs among parents with healthy-weight vs overweight/obesity. The findings of this review imply some differences between parents with overweight/obesity and healthy-weight and the use of some food-related parenting practices, however they should be interpreted with caution since research remains limited and is generally methodologically weak. The review highlights opportunities for further research and to improve current measures of FPPs and help clarify current study findings.

For very first time, we report the synthesis of 8-(2-methoxyphenyl)-6-methyl-2-(1-methyl-1H-benzo[d]imidazol-2-yl)quinoline 1. This was achieved in several steps, including usage of Suzuki reaction for functionalization of 2-(1H-benzo[d]imidazol-2-yl)quinoline moiety. The new compound exhibits blue fluorescence. Its structure was confirmed with 1D- and 2D-NMR spectroscopy, IR-spectroscopy, high-resolution mass spectrometry and X-ray analysis.

Fe[C5H5N]2[N(CN)2]2 (1) was synthesized from a reaction of stoichiometric amounts of NaN(CN)2 and FeCl2·4 H2O in a methanol/pyridine solution. Single-crystal and powder diffraction show that 1 crystallizes in the monoclinic space group I2/m (no. 12), different from Mn[C5H5N]2[N(CN)2]2 (P21/c, no. 14) due to tilted pyridine rings, with a = 7.453(7) Å, b = 13.167(13) Å, c = 8.522(6) Å, β = 114.98(6)° and Z = 2. ATR-IR, AAS, and CHN measurements confirm the presence of dicyanamide and pyridine. Thermogravimetric analysis shows that π-stacking interactions of the pyridine rings play an important role in structural stabilization. Based on DFT-optimized structures, a chemical bonding analysis was performed using a local-orbital framework by projection from a plane-wave basis. The resulting bond orders and atomic charges are in good agreement with the expectations based on the structure analysis. SQUID magnetic susceptibility measurements show a high-spin state FeII compound with predominantly antiferromagnetic exchange interactions at lower temperatures.

Significant efforts are being made across academia and industry to better characterize lithium-ion battery cells as reliance on the technology for applications ranging from green energy storage to electric mobility increases. The measurement of short-term and long-term volume expansion in lithium-ion battery cells is relevant for several reasons. For instance, it provides information about the quality and homogeneity of battery cells during charge and discharge cycles, as well as aging over it’s lifetime. The expansion measurements are useful for the evaluation of new materials and the improvement of end-of-line quality tests during cell production. These measurements may also indicate the safety of battery cells by aiding in predicting state of charge and state of health over the lifetime of the cell. Expansion measurements can also assess inhomogeneities on the electrodes and defects such as gas accumulation and lithium plating. In this review, we first establish the known mechanisms through which short term and long term volume expansion in lithium-ion battery cells occurs. We then explore the current state-of-the-art for both contact and non-contact measurements of volume expansion. This review compiles existing literature to outline the various options available to researchers aiming to make ex situ volume expansion measurements by doing post mortem analyses on individual components and in operando measurements on entire battery cells. Finally, we discuss the different considerations when selecting an appropriate measurement technique. The selection of the optimal method for measuring battery cell expansion depends on the objective of the characterization, duration, required resolution, and repeatability of results. Costs and required space for the measurement equipment are also considered.

Lymphoma is one of the most common cancers worldwide, categorized into Hodgkin lymphoma and non-Hodgkin lymphoma. 18F-fluorodeoxyglucose positron emission tomography (FDG PET) has become an essential imaging tool for evaluating patients with lymphoma in terms of initial diagnosis, staging, prognostication, and treatment response assessment. Recent advancements in imaging technology and methodologies, along with the development of artificial intelligence, have revolutionized the evaluation of complex imaging data, enhancing the diagnostic and predictive power of PET in lymphoma. However, FDG is not cancer-specific, but it primarily reflects glucose metabolism, which has prompted the investigation of alternative PET tracers to address this limitation. Novel PET radiotracers, such as fibroblast activation protein inhibitors targeting the tumor microenvironment, have recently shown promising results in evaluating various malignancies compared to FDG PET. Furthermore, with the rapid advancements in immunotherapy and the favorable imaging properties of 89Zr, immunoPET has emerged as a promising modality, offering insights into the functional and molecular status of the immune system. ImmunoPET can also facilitate the development of new antibody therapeutics and radioimmunotherapy by providing pharmacokinetic and pharmacodynamic data. This review provides comprehensive insights into the current clinical applications of FDG PET in lymphoma, while also exploring novel PET imaging radiotracers beyond FDG, discussing their mechanisms of action and potential impact on patient management.

Wild-type p53 cancer therapy-induced senescent cells frequently engulf and degrade neighboring ones inside a massive vacuole in their cytoplasm. After clearance of the internalized cell, the vacuole persists, seemingly empty, for several hours. Despite large vacuoles being associated with cell death, this process is known to confer a survival advantage to cancer engulfing cells, leading to therapy resistance and tumor relapse. Previous attempts to resolve the vacuolar structure and visualize their content using dyes were unsatisfying for lack of known targets and ineffective dye penetration and/or retain. Here, we overcame this problem by applying optical diffraction tomography and Raman spectroscopy to MCF7 doxorubicin-induced engulfing cells. We demonstrated a real ability of cell tomography and Raman to phenotype complex microstructures, such as cell-in-cells and vacuoles, and detect chemical species in extremely low concentrations within live cells in a completely label-free fashion. We show that vacuoles had a density indistinguishable to the medium, but were not empty, instead contained diluted cell-derived macromolecules, and we could discern vacuoles from medium and cells using their Raman fingerprint. Our approach is useful for the non-invasive investigation of senescent engulfing (and other peculiar) cells in unperturbed conditions, crucial for a better understanding of complex biological processes.

To investigate the impact of radiologic experience on the diagnostic accuracy of computed tomography CT vs. magnetic resonance imaging (MRI) reporting for liver metastases of pancreatic ductal adenocarcinoma (LM of PDAC). Intra-individual CT and MRI examinations of 112 patients with clinically proven LM of PDAC were included. Four radiologists with varying years of experience (A > 20, B > 5, C > 1 and D < 1) assessed liver segments affected by LM of PDAC, as well as associated metastases occurring in each patient. Their sensitivity and specificity in evaluating the segments were compared. Cohen's Kappa (κ) for diagnosed liver segments and Intra-class Correlation Coefficients (ICC) for the number of metastatic lesions in each patient were calculated. The radiologists’ sensitivity and specificity for the CT vs. MRI were, respectively: Reader A -94.4, 90.3% vs. 96.6, 94.8%; B - 86.7, 79.7% vs. 83.9, 82.0%; C - 78.0, 76.7% vs. 83.3, 78.9% and D - 71.8, 79.2% vs. 64.0, 69.5%. Reviewers A and B achieved greater agreement in assessing results from the MRI (κ = 0.72, p < 0.001; ICC = 0.73, p < 0.001) vs. the CT (κ = 0.58, p < 0.001; ICC = 0.61, p < 0.001), in contrast to readers C and D (MRI: κ = 0.34, p < 0.001; ICC = 0.42, p < 0.001, and CT: κ = 0.48, p < 0.001; ICC = 0.59, p < 0.001). Our results indicate that accurate diagnosis of LM of PDAC depends more on radiologic experience in MRI over CT scans.

Amidst worsening climate change, drought stress imperils global agriculture, jeopardizing crop yields and food security, necessitating urgent exploration of sustainable methods like biopriming, harnessing beneficial microorganisms to bolster plant resilience. Recent research has revealed diverse biological compounds with versatile applications produced by Schizophyllum commune, rendering this fungus as a promising contender for biopriming applications. For the first time this study aimed to investigate,the potential of S. commune exo- (EPSH) and intra-PSH (IPSH), isolated from two strains: Italian (ITA) and Serbian (SRB) under submerged cultivation, in enhancing the resilience of Pisum sativum L. seeds through biopriming technique. Testing of seed quality of bioprimed, hydroprimed, and unprimed seeds was done using a germination test, under optimal and drought conditions. In optimal conditions, the IPSH SRB increased germination energy by 5.50% compared to the control, while the highest percentage of germination (94.70%) was shown after biopriming with PSH isolated from the ITA strain. Additionally, all assessed treatments resulted in a boost in seedling growth and biomass accumulation, where the ITA strain demonstrated greater effectiveness in optimal conditions, whereas the SRB strain showed superiority in drought conditions. The drought tolerance indices increased significantly in response to all examined treatments during the drought, with EPSH ITA (23.00%) and EPSH SRB (24.00%) demonstrating the greatest effects. Results demonstrate a significant positive influence of fungal PSH, indicating their potential as biopriming agents and offers insights into novel strategies for agricultural resilience in the face of changing environmental conditions.

Dysregulation of the Cyclin-dependent kinase 8 (CDK8) activity has been associated to many diseases including the colorectal and breast cancer. As usual in the CDK family, the activity of CDK8 is controlled by a regulatory protein called cyclin C (CycC). But while human CDK family members are generally activated in two steps that is, the binding of the cyclin to CDK and the phosphorylation of a residue in the CDK activation loop, CDK8 does not require the phosphorylation step to be active. Another peculiarity of CDK8 is its ability to be associated to CycC while adopted an inactive form. These specificities raise the question of the role of CycC in the complex CDK8-CycC, which appears to be more complex than for the other members of CDK family. Through MD simulations and binding free energy calculations, we investigated the effect of CycC on the structure and dynamics of CDK8 on the one hand, and the structural molecular basis of the protein-protein interaction between the two partners on the other hand. We found that CycC has a stabilizing effect on CDK8 and identified specific interaction hotspots within its interaction surface compared to other human CDK/Cyc pairs. Targeting these specific interaction hotspots could be a promising approach in terms of specificity, to effectively disrupt the interaction between CDK8. The simulation of the conformational transition from the inactive to the active form of CDK8 suggests that the residue Glu99 of the CycC may assume the role of the missing phosphorylation step in the activation mechanism of CDK8. In a more general view, these results point the importance of keeping the CycC in computational studies when studying the human CDK8 protein in both the active and the inactive form.

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

Resveratrol (RSV), a naturally occurring phytoalexin, is the most important stilbenoid synthesized by plants, as a defense mechanism, in response to microbial aggression, toxins or ultraviolet radiation. RSV came to the attention of researchers both as a potential chemopreventive agent and a possible explanation for the low incidence of cardiovascular disease (CVD) in French people with a high-fat diet. RSV is mainly administered as a food supplement, its properties being evaluated in vitro or in vivo, on various experimental models. RSV modulates signaling pathways that limit the spread of tumor cells, protects nerve cells from damage, is useful in the prevention of diabetes, and generally acts as an anti-aging natural compound. It was highlighted that RSV could ameliorate the consequences of an unhealthy lifestyle caused by an exaggerated caloric intake. This paper reviews the evidence supporting the beneficial effect of RSV for various pathological conditions, e.g., neoplastic diseases, neurodegeneration, metabolic syndrome, diabetes, obesity, CVDs, immune diseases, bacterial, viral, and fungal infections. The study also focused on the chromatographic analysis of trans-RSV (tRSV) in Romanian wine samples, providing a comprehensive overview of tRSV content across different types of wine.

The paper provides a discussion on the results of studies of the effect exerted by combined degradation factors typical of four types of wear: abrasion, impact-abrasion, tribocorrosion, and impact-abrasion-corrosion, conducted for chain wheels made of Ni-Cu alloyed Austempered Ductile Iron. The studies consisted in determining the content of retained austenite in the structure of the cast irons in question, establishing the measures of wear following wear testing, and identifying basic surface degradation mechanisms observed in the chain wheels tested following multifactorial wear processes. The chain wheels made of ADI were found to have sustained the greatest damage under the impact-abrasion-corrosion (three-factor) wear scenario, while the wear was least advanced in the abrasion (one-factor) wear case. Another observation derived from the studies is that the combined effect of dynamic forces, corrosion, and quartz sand-based abrasives causes increased surface degradation in the cast iron grades taken into consideration compared to processes characterised by a reduced number of degradation factors (i.e. one- or two-factor wear processes). Additional hardness tests and XRD analyses have revealed a distinctive effect attributable to combined degradation factors on the surface hardness increase value and implied that bench testing was followed by phase transition.

Focal adhesions (FAs) play a crucial role in cell spreading and adhesion, and their autophagic degradation is an emerging area of interest. Our study investigates the role of Thrombospondin Type 1 Domain-Containing Protein 1 (THSD1) in regulating autophagy and FA stability in brain endothelial cells, shedding light on its potential implications for cerebrovascular diseases. Our research reveals a physical interaction between THSD1 and FAs. Depletion of THSD1 significantly reduces FA numbers, impairing cell spreading and adhesion, in an autophagy-dependent manner. Intriguingly, THSD1-mediated autophagy activation operates independently of changes in mTOR and AMPK activation, implying that THSD1 primarily governs FA dynamics rather than serving as a global regulator of nutrient and energy status. Interestingly, THSD1 negatively regulates Beclin 1, a central autophagy regulator, at FAs through interactions with focal adhesion kinase (FAK). The loss of THSD1 diminishes FAK activity, consequently relieving its inhibitory phosphorylation on Beclin 1. This, in turn, promotes the complex formation between Beclin 1 and ATG14, a critical event for the activation of the autophagy cascade. In summary, our findings identify THSD1 as a novel regulator of autophagy that degrades FAs in brain endothelial cells. This underscores the distinctive nature of THSD1-mediated, cargo-directed autophagy and its potential relevance to vascular diseases due to the loss of endothelial FAs. Investigating the underlying mechanisms of THSD1-mediated pathways holds promise for discovering novel therapeutic targets in vascular diseases.

Aquaculture is expected to play a vital role in solving the challenge of sustainably providing the growing world population with healthy and nutritious food. Pathogen outbreaks are a major risk for the sector, so early detection and a timely response are crucial. This can be enabled by monitoring of pathogen levels in aquaculture facilities. This paper describes a photonic biosensing platform based on silicon nitride waveguide technology with integrated active components, which could be used for such applications. Compared to the state of the art, the current system presents improvements in terms of miniaturization of the Photonic Integrated Circuit (PIC), and the development of wafer level processes for hybrid integration of active components and for material-selective chemical and biological surface modification. Furthermore, scalable processes for integrating the PIC in a microfluidic cartridge have been developed, as well as a prototype desktop readout instrument. Three bacterial aquaculture pathogens (Aeromonas salmonicida, Vagococcus salmoninarum, and Yersinia ruckeri) were selected for assay development. DNA biomarkers were identified, corresponding primer-probe sets designed, and qPCR assays developed. The biomarker for Aeromonas was also detected using the hybrid PIC platform. This is the first successful demonstration of biosensing on the hybrid PIC platform.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, and despite advances in treatment, survival rates are still low; therefore, the development of novel drugs is imperative. Acetylcorynoline (ACN) is derived from Corydalis ambigua. The effect of ACN on colon cancer is still unknown. Therefore, we investigated its potential effects. Our data showed that ACN inhibited cell viability and proliferation. Moreover, ACN induced apoptosis and cell cycle arrest by inhibiting cell growth. In the present study, we hypothesized that ACN regulates c-Myc through CNOT2 or MID1IP1. ACN reduced the protein expression of oncogenic genes, decreased c-Myc half-life, and rapidly inhibited the serum stimulation response. Moreover, knockdown of CNOT2 and MID1IP1 with ACN increased apoptosis and further reduced the expression of oncogenes. In addition, ACN exhibited a synergistic effect with low-dose of 5-fluorouracil (5-FU) and doxorubicin (Dox). Collectively, our data demonstrates that ACN inhibited c-Myc expression through CNOT2 and MID1IP1 and induced apoptosis. These findings indicate the potential of ACN as a therapeutic agent against colon cancer.

As renewable energy generation prediction systems have been introduced into the energy trading market, accurate prediction of solar photovoltaic (PV) energy generation has become a crucial challenge for ensuring stable trade of variable energy. Therefore, it is essential to quantitatively investigate and analyze current prediction technology and develop more advanced prediction systems. In this study, three models for predicting PV energy generation were investigated. Multiple regression, random forest, and gradient boosting machine (GBM) models were con-structed for 15 utility-scale power plants throughout South Korea. Model performance was evaluated in terms of root mean square error (RMSE) and mean absolute error (MAE). The multiple regression-based model had an RMSE of 12.00% and MAE of 9.06%. The random forest model had an RMSE of 11.69% and MAE of 8.61%. The GBM model had an RMSE of 11.34% and MAE of 8.18%, indicating its superior accuracy among the three models in predicting PV energy generation. These findings provide valuable insights that may contribute to the development of advanced PV energy generation models and their application in grid operations.

The inter-subspecific crossing between indica and japonica subspecies in rice have been utilized to improve the yield potential of temperate rice. In this study, a comparative study of the genomic regions in the eight high-yielding varieties (HYVs) was conducted with those of the four non-HYVs. The Next-Generation Sequencing (NGS) mapping on the Nipponbare reference genome identified a total of 14 common genomic regions of japonica-originated alleles. Interestingly, the HYVs shared japonica-originated genomic regions on nine chromosomes, although they were developed through different breeding programs. A panel of 94 varieties was classified into four varietal groups with 38 single nucleotide polymorphism (SNP) markers from 38 genes residing in the japonica-originated genomic regions and 16 additional trait-specific SNPs. As expected, the japonica-originated genomic regions were only present in the japonica (JAP) and HYV groups, except for Chr4-1 and Chr4-2. The Wx gene, located within Chr6-1, was present in the HYV and JAP variety groups, while the yield-related genes were conserved as indica alleles in HYVs. The japonica-originated genomic regions and alleles shared by HYVs can be employed in molecular breeding programs to further develop the HYVs in temperate rice.

Ulmus species have been widely used in Korean folk medicine because of their anti-inflammatory and antimicrobial properties. We intended to investigate the wound healing effect of the powder of Ulmus parvifolia (UP) root bark in a mouse wound healing model. We also determined the mechanisms of effects of Ulmus parvifolia (UP) in skin and skin wound healing effect using keratinocyte model. in vivo experiments showed that the wound lesions in the mice decreased by U. parvifolia with 200 mesh size of root bark powder and significantly reduced by treatment with UP, compared with those treated with U. macrocarpa (UM). Results from in vitro experiments also revealed that UP extract promoted the migration of human skin keratinocytes. UP powder treatment upregulated the expression of the matrix metalloproteinase-2 and -9 protein and significantly increased transforming growth factor (TGF)-β levels. We confirmed that topical administration of the bark powder of exerted a significant effect on skin wound healing by upregulating the expression of MMP and transforming growth factor-β. TGF-β In, Our study suggests that U. parvifolia may be a potential candidate for skin wound healing including epidermal skin rejuvernation.

The ongoing challenge to ensure a sustainable and affordable energy supply forces industrial companies to implement appropriate measures. These measures typically lead to an increased system complexity, which has to be addressed during operation. Whereas existing approaches from the field of supervisory and optimal control appear to be capable of mastering this issue, these are still not adopted in industry. Therefore, this work presents a procedure model for the systematic development of application-oriented operating strategies for industrial energy supply systems. The procedure model combines research approaches from the fields of sequencing control and approximate MPC to extract rule-based operating strategies. By splitting the procedure model into five phases, expert knowledge can be integrated in a target-oriented manner. Subsequently to the description, the procedure model is exemplary applied to the example of an industrial heating supply system. Throughout an optimization study, the developed operating strategy is compared to a MPC strategy as well as a baseline strategy. Whereas the conventional MPC approach is the upper bound with regard to optimality, the developed operating strategy is able to generate comparable results. Compared to the baseline strategy, a relative reduction in operating expenses of 5.4 % to 37.0 % are achieved in this specific use case.

The purpose of this study was to analyze the cross-linguistic influence of previously learned languages and working memory capacities on the vocabulary performance of two different typological languages. The objectives of this study were (1) to compare the working memory capacities of bilingual adults in relation to the vocabulary performance of two different languages never learned by the participants, and (2) to analyze to what extent the typology of previously learned languages influences working memory capaci-ties in relation to the vocabulary performance of French and Nahuatl. A group of 43 Mexican-Spanish college students participated in this experimental study. The participants completed a series of working memory tasks in Nahuatl and French. The results showed that working memory capacities were lower in Nahuatl than in French. Thus, a correlation was found between their first and second language and vo-cabulary performance in French. We can consider the influence of previously learned languages as a significant factor in vocabulary acquisition in accordance with the participants' working memory capacities.

Natural Gas (NG) processing is a prominent industrial separation process. Among the available techniques, the innovative membrane process shows potential for efficient removal of impurities, including carbon dioxide (CO₂). This study focuses on utilizing breakthroughs in membrane separation to drive sustainable CO₂ extraction from natural gas. Through comprehensive research and analysis, we explore the effectiveness and feasibility of membrane-based systems in removing CO₂ impurities from NG, thus promoting greener and more sustainable industrial practices. Our findings underscore the transformative nature of membrane separation technology, presenting new possibilities for a more environmentally-friendly and sustainable approach to CO₂ extraction from natural gas.Natural Gas (NG) processing utilizes various techniques for impurity removal, with the membrane process emerging as a promising option for efficient carbon dioxide (CO₂) extraction. This research proposes the integration of a simple mathematical model into ASPEN HYSYS to design a membrane system for CO₂/CH₄ separation. The study also investigates parameter sensitivities by altering operating conditions, such as feed composition and pressure, as well as membrane properties, including selectivity. By analyzing these variables, we aim to optimize the performance and efficiency of the membrane system, facilitating the sustainable extraction of CO₂ from NG. The findings contribute to advancing the design and operation of membrane-based processes for CO₂ separation, paving the way for greener and more sustainable industrial practices. In addition, this study explores various configurations for optimizing the design of the membrane system, including single-stage with and without recycling as well as double-stage configurations. The investigation demonstrates that methane recovery can be enhanced through the recycling of the permeate stream and by implementing a double stage membrane system. These findings highlight the potential for improving the efficiency and performance of the membrane system, enabling higher methane recovery rates. By considering different configurations, this research contributes to the development of more effective and sustainable CO₂ extraction processes from natural gas.

Airborne wind energy (AWE) systems use tethered flying devices to harvest higher-altitude winds to produce electricity. For a successful deployment of these systems, it is crucial to understand how the public perceives them. If public concerns about the technology are not taken seriously, implementation could be delayed or, in some cases, prevented, resulting in increased costs for project developers and a lower contribution of the sector to renewable energy targets. This literature review assessed the current state of knowledge on public responses to AWE. An exhaustive literature search led to the identification of 40 relevant publications that were reviewed. The literature assumed that the safety, visibility, acoustic emissions, ecological impacts, and the siting of AWE systems shape public responses to the technology. The reviewed literature views people’s responses to AWE very optimistically but lacks scientific evidence to back up its claims. It seems to overlook that the influence of AWE’s characteristics (e.g., visibility) on public responses will also depend on a range of situational and psychological factors (e.g., people’s general attitude towards AWE, the public’s trust in project developers). Therefore, empirical social scientific research is needed to increase the field’s understanding of public responses to AWE and thereby facilitate deployment.

Driving simulators are widely used for understanding human-machine interaction, driver behavior and in driver training. The effectiveness of simulators in these process depends largely on their ability to generate realistic motion cues. Though the conventional filter-based motion cueing strategies have provided reasonable results, these methods suffer from poor workspace management. To address this issue, linear MPC-based strategies have been applied in the past. However, since the kinematics of the motion platform itself is non-linear and the required motion varies with the driving conditions, this approach tends to produce sub-optimal results. This paper presents a nonlinear MPC-based algorithm which incorporates the nonlinear kinematics of the Stewart platform within the MPC algorithm in order to increase the cueing fidelity and utilize maximum workspace. Further, adaptive weights-based tuning is used to smoothen the movement of the platform towards its physical limits. Full-track simulations were carried out and performance indicators were defined to objectively compare the response of the proposed algorithm with classical washout filter and linear MPC-based algorithms. The results indicate a better reference tracking with lower root mean square error and higher shape correlation for the proposed algorithm. Lastly, the effect of the adaptive weights-based tuning was also observed in the form of smoother actuator movements and better workspace utilization.

The efficacy and safety of organic UV-filters could benefit from their incorporation into lipid nanoparticles because of the ability of such carriers to reflect solar radiations, thus acting synergically as physical sunscreens. In this work, bemotrizinol (BMTZ), a broad-spectrum UV-filter, was loaded into nanostructured lipid carriers (NLC) whose lipid matrix contained different oils to assess the effects of the lipid core composition on the properties of the resulting NLC. Subsequently, the effects of incorporating different concentrations of optimized BMTZ-loaded NLC on the technological properties of O/W emulsions (pH, viscosity, spreadability, occlusion factor, in vitro BMTZ release and skin permeation, in vitro sun protection factor) were assessed. Optimized BMTZ-loaded NLC showed mean size=190.6±9.8 nm, PDI=0.153±0.013, ζ-potential=-10.6±1.7 mV, loading capacity=8% w/w. The incorporation of increasing concentrations of optimized BMTZ-loaded into emulsions provided slight increase of spreadability, lower viscosity and no change of pH, occlusion factor and BMTZ release compared to the control. No BMTZ skin permeation was observed from all formulations. About 20% increase of sun protection factor values was obtained for vehicles containing BMTZ-loaded NLC. Therefore, BMTZ-loaded NLC incorporation into emulsions could be a promising strategy to develop safer and more effective sunscreen formulations.

Flexible wearable pressure sensors offer numerous benefits, including superior sensing capabilities, a lightweight and compact design, and exceptional conformal properties, making them highly sought after in various applications including medical monitoring, human-computer interaction, and electronic skin. Because of their excellent characteristics, such as simple fabrication, low power consumption, and short response time, capacitive pressure sensors have received widespread attention. As a flexible polymer material, polydimethylsiloxane (PDMS) is widely used in the preparation of dielectric layers for capacitive pressure sensors. The Young's modulus of the flexible polymer can be effectively decreased through the synergistic application of sacrificial template and laser ablation techniques, thereby improving the functionality of capacitive pressure sensors. In this study, a novel sensor was developed through a series of processes including sacrificial template method using NaCl microparticles, CO₂ laser ablation, and sandwiching a porous PDMS dielectric layer between two flexible electrodes to create a capacitive pressure sensor. The sensor demonstrates a sensitivity of 0.694 kPa-1 within the pressure range of 0-1 kPa, and can effectively detect pressures ranging from 3 Pa to 200 kPa. The sensor demonstrates stability for up to 500 cycles, with a rapid response time of 96ms and a recovery time of 118ms, coupled with a low hysteresis of 6.8%. Furthermore, our testing indicates that the sensor possesses limitless potential for use in detecting human physiological activities and signaling emergencies.

Sesame seeds and their edible oil are highly nutritious and rich in mono- and polyunsaturated fatty acids. Bioactive compounds such as sterols, tocopherols, and sesamol provide significant medicinal benefits. The high oil content (50%) and favorable mono-and polyunsaturated fatty acids balance, as well as sesame's resilience to water stress makes, make it a promising candidate for global agricultural expansion. However, sesame production faces challenges such as low yields, poor response to agricultural inputs, and losses due to capsule dehiscence. To enhance yield, traits like determinate growth, dwarfism, high harvest index, non-shattering capsules, and photoperiod sensitivity are needed. These traits can be achieved through variation or induced mutation breeding. Traditional breeding methods often result in unwanted genetic changes. The CRISPR/Cas9 technology has the potential to suppress detrimental alleles and improve the fatty acid profile by inhibiting polyunsaturated fatty acid biosynthesis. Even though sesame is an orphan crop, it has entered the genomic era, with available sequences assisting molecular breeding efforts. This progress aids in associating single nucleotide polymorphisms (SNPs) and simple sequence repeats (SSRs) with key economic traits, as well as identifying genes related to adaptability, oil production, fatty acid synthesis, and photosynthesis. Additionally, transcriptomic studies can reveal genes involved in abiotic stress responses and adaptation to diverse climates. Quantitative trait loci (QTL) mapping can identify loci linked to crucial traits such as capsule size, seed count per capsule, and capsule number per plant. This paper reviews recent advances in sesame breeding, discusses ongoing challenges, and explores potential strategies for future improvement. Hence, integrating advanced genomic tools and breeding strategies provides promising ways to enhance sesame production to meet global demands.

Healthcare professionals constantly face situations that reflect ecosystems’ degradation. These can negatively affect their mental health. Research suggests that hope and resilience can play an important role in this scenario, since they are related to/predict mental health in highly heterogeneous samples (considering geography, age, profession, health, etc.). In this context, the aims of the present study are: to characterize and explore the relationship between hope, resilient coping and mental health of Portuguese healthcare professionals. Using Google Forms, 276 healthcare professionals answered to the GHQ-28, the (adult) Trait Hope Scale, and the Brief Resilient Coping Scale (cross-sectional study). The minimum and maximum possible scores were reached, with the exception of the maximum score of GHQ-28-Total. Regarding Hope, 19.6% scored below the midpoint (M=43.46, SD=11.97); 29.3% revealed low resilience (M=14.93, SD=4.05); and the average of 4 of the 5 Mental Health scores (exception: Severe Depression) indicates the probability of a psychiatric case. Hope correlated with Social Dysfunction and GHQ-28-Total; resilient coping proved to be a (weak) predictor of 4 of the 5 GHQ-28 indicators (exception: Severe depression). The results support the need to promote the sample's mental health, hope and resilient coping. They also suggest that stimulating resilient coping may contribute to improving healthcare professionals’ mental health.

In 2011, commercial aviation contributed approximately 3.5% of global anthropogenic climate change through the emission of greenhouse gases during flight and operational non-CO2 climate effects. Over the last few years, numerous aviation-related organisations have set goals to reduce aviation’s climate impact. These goals, however, lack alignment, are poorly or ambiguously defined, or are internally inconsistent. This increases uncertainty about what aviation should work towards, how various stakeholders can contribute, and introduces problems with respect to accountability. In order to address this issue, this paper presents a comprehensive definition of a climate neutral air transport system as an “air transport system of which the climate effects of all its greenhouse gases and non-carbon dioxide effects throughout the entire life-cycle of each element of the system is balanced”. The proposed definition spans relevant system and encompasses all life cycle phases. To achieve a climate neutral air transport system by 2050, all life-cycle greenhouse gas emissions and non-CO2 climate effects remaining after in-sector reduction should be neutralised, as should all remaining non-CO2 climate forcing from emissions prior to 2050. Clarity on governance is furthermore needed, as the goal and associated targets proposed should be adopted globally.