The implementation of morphing wing mechanisms holds promise in enhancing aircraft perfor-mance, as indicated in current literature. The Clean Sky 2 AirGreen 2 European project is currently conducting ground and wind tunnel tests to validate innovative studies on morphing wing structures. The project aims to showcase the effectiveness of these morphing architectures on a potentially flying demonstrator at true scale. This article describes design methodology and struc-tural testing of a scaled morphing flap structure capable of 3 different morphing modes required for low-speed (take-off/landing) and high-speed (cruise) conditions. A significant scale factor of 1:3 was selected to enhance the importance and relevance of the wind tunnel test campaign. Geometrical scaling to the real flap prototype was deemed impractical due to limitations associated with scaling the embedded mechanisms and actuators responsible for shape changing. Static analyses were performed using the finite element method to address the most critical loads determined through three-dimensional CFD analysis. The Finite Element (FE) analysis results were briefly outlined, and comparisons were drawn between the obtained results and the empirical data collected during the structural test. Good correlations were observed between the results and numerical predictions, encompassing static deflections under applied loads and elastic deformations. Consequently, the modeling approaches utilized during the design and testing phases were considered highly suc-cessful. Therefore, based on the results extrapolated from simulations under ultimate load condi-tions relevant to the wind tunnel test campaign, the scaled flap prototype was deemed suitable for testing.

This study, conducted with meticulous attention to detail, comprehensively examines the state of plants and their adaptation to Kazakhstan's extra-arid climatic zone of the Mangistau. It uses the collections of woody plants from the Mangyshlak Experimental Botanical Garden in Aktau as a case study and extrapolates the results to the entire region. The study area is arid and unsuitable for many plants, so examining physiological adaptation mechanisms and strategies for preserving plants in unfavourable conditions is crucial. The study employed a range of methods, including the measurement of the intensity of transpiration, leaf hydration, and the content of chlorophyll A, B, and carotenoids. These methods were chosen for their proven effectiveness in similar studies and their ability to provide accurate and reliable data. The samples were also assessed using a point system for resistance to drought, phytophagy, gas tolerance, salt tolerance, winter hardiness, and soil fertility. The results obtained and entered into the IEBG platform “DinTseR” to assess the value of the introduction using a diagnostic scale revealed a high variability (up to 51.7-52.2%) of physiological indicators of growth and development. The highest values of transpiration intensity were observed in deciduous trees and shrubs, rose varieties (205-243 mg/g fresh leaf mass per hour), leaf water content - in climbing plants (68.9%), chlorophyll A and B content - in deciduous plants, and plants - old trees, fruit trees and varietal roses (3.46-3.93 and 1.34-1.84%). Their concentration in coniferous species is almost two times lower (0.63%). A correlation was also made between various significant factors. Twenty regression equations and forecasts have been identified that can be used to diagnose and assess resistance, thereby reducing the cost of determining the introduction value in the conditions of Mangistau. These findings are essential in understanding and preserving the unique flora of the Mangistau region.

This article presents the analysis of the allocation of important plant areas (IPA), which urgently identifies the most valuable sites for protecting plant objects. The study is based on a comprehensive inventory of the species composition of plants in the flora of the Western Karatau Ridge and the Mangyshlak Peninsula (arid regions)- key sites Akmysh, Samal, and Kogez, considered standard and the best preserved with natural vegetation cover. The flora of these critical sites was analysed using a combination of field surveys, herbarium studies, and a literature review. The results revealed a rich biodiversity, with 104 species from 82 genera and 33 families. Most species belong to 9 families, making up 60.6% of the total taxa. By the nature of life forms, perennial herbaceous plants dominate in all key sites (30 species, 50.0%). The eco-phylogenetic spectrum showed that a significant share of the flora of the studied IPAs is made up of xerophytes (21 species, 35%) and xeromesophytes (9 species, 15%); desert and mountain-steppe species prevail (53.0%). Rare, endangered and Red Book species account for 10-21.3% of those growing in the region. Regarding economic value, fodder, ornamental, honey, medicinal and food species dominate. The Shannon, Simpson, and Jaccard indices assessed alpha-beta and gamma diversity. The index showed that biodiversity in the Samal and Kogez sites is higher and more evenly distributed compared to the Akmysh site. The Whittaker, Harrison and Cody indices confirm significant differences in the species composition between the sites. In light of these compelling results, a clear and urgent call to action is proposed to allocate these areas to the IPA category, a crucial step towards ensuring the long-term existence of natural biocenoses.

The study explores how different dimensions of perfectionism influence psychological well-being (PWB) in emerging adults. Literature has deepened the relationships between maladaptive perfectionism (e.g., excessive self-criticism, perceived discrepancy from the standards) and low PWB. Less is known about whether and how adaptive perfectionism (e.g., pursuing personal standards) relates to PWB. Secondly, the study has investigated whether self-compassion (i.e., self-benevolence, seeing personal imperfections as a common condition) may mediate the relationships between adaptive/maladaptive perfectionism and PWB. Participants (N=217, 18-35 y. o.) completed self-report questionnaires measuring: adaptive/maladaptive perfectionism (Almost Perfect Scale-Revised, APS-R: high standards and order/discrepancy, respectively), PWB, and self-compassion (SCS). Adaptive perfectionism resulted associated with PWB, particularly higher presence of purpose in life, environmental mastery, self-acceptance, and personal growth. Conversely, discrepancy resulted the most robust predictor of low PWB (β=-.68), followed by high standards with a positive direction (β=.23; Rc²=.514, p<.001). A strong negative association emerged between discrepancy and SCS (r=-.67, p<.001). A mediation analysis shows that self-compassion has an indirect effect reducing the strength of the relationship between discrepancy and low PWB. Results suggest focusing on self-compassion as a buffer factor that reduces the negative impact of maladaptive perfectionism on psychological well-being. Implications for education and health psychology are discussed.

Background and objectives: The fact that the results of troponin and Nt-proBNP interfere from biotin caused some commercial firms to update their measurement methods. In particular, the clinical incompatibility of cardiac test results may affect the risk of morbidity and mortality. The aim of this study is to investigate the interference effects of 7 different contrast agents on cardiac markers (Troponin-I, Nt-proBNP, Mass CK-MB, CK, AST, LDH) and coagulation tests (PT, APTT). Materials and Methods: Seven different contrast medias were added into control materials by using interference protocol. Concentration of PT, APTT, CK, AST, LDH, Mass CK-MB, Troponin-I, Nt-proBNP were measured by Sysmex CS-2100, Abbott c16000, Siemens Centaur XP and AFİAS-6 analyzer. The amount of deviations from target values were calculated. Results: 7 different contrast medias caused negative interference in troponin levels between 57.43% and 62.87%. It was found that different contrast medias produced false negativity in the Nt-proBNP test ranging from 6.11% to 96.01%. Enzymes and coagulation tests have been less affected. Conclusions: Different contrast medias may cause false negative cTnI and Nt-proBNP. Therefore, the contrast medias which causes the least interference should be preferred. The results of samples taken in the first hour of contrast imaging should be interpreted with care.

Objective: to retrospectively evaluate the incidence rate (IR) of echocardiographic signs suspected for pulmonary hypertension (PH) in Systemic sclerosis (SSc) patients after the introduction of a combination therapy with bosentan and sildenafil for treatment or prevention of digital ulcers. Methods: patients attending the Scleroderma Unit of the Universital Hospital of Careggi from July 2010 to July 2023 were enrolled. Patients older than 18 years old, with an history of digital ulcers, treated with bosentan and sildenafil in combination for at least 12 months were included. Patients with a diagnosis of PH preceding the introduction of the therapy were excluded. Demographical data, disease duration, laboratoristic and instrumental data (pulmonary function tests, echocardiographic estimation of pulmonary artery pressure (PAPs) and ultrasonographic value of renal resistive index) were collected. The IR of echocardiographic signs suspected for pulmonary hypertension and their 95% confidence interval were calculated in events/1000 patients-years.Results: forty-seven patients were enrolled; mean disease duration was 12,14 years (SD 5,87). Mean duration of the combination treatment was 78.33 (SD 41.37) months and total at-risk time was 3525 months. Two patients (4,2%) presented echocardiographic signs of PH (sPAP 50 mmHg and 40 mmHg); the IR was calculated to be 6.8/1000 patients-years (95% CI 6,02-7,7). In one of the 2 patients RHC excluded PAH, while the other patient refused to undergo to RHC and PAH could not be confirmed/excluded. A stability of PFTs and echocardiografic PAPs was observed during the observation time. Conclusions: the results of this retrospective study suggest that combination therapy with endothelin receptor antagonist and Phosphodiesterase-5 (PDE5) inhibitors could help in preventing PAH in SSc; prospective case-control studies on larger population are needed to improve knowledge in this field.

Daridorexant, as the first Dual Orexin Receptor Antagonist (DORA) marketed in Europe, offers a novel therapeutic approach to insomnia. However, data regarding its real-world safety are scarce. Thus, the aim of this study was to assess its safety profile using a large-scale pharma-covigilance database. Daridorexant-related Adverse Drug Reaction (ADR) reports from the FDA Adverse Event Reporting System were scrutinized, and ADRs were selected using reporting odds ratio (ROR) as a measure of disproportionality. Frequencies of events related to daridorexant were compared to all other drugs (reference group, RG1) and only to other DORAs (RG2). Only significant disproportionalities to both RGs were evaluated in-depth. A total of 845 dari-dorexant-related reports were selected; nightmares (n = 146; Dari vs. RG1: ROR = 113.74; 95%CI[95.13, 136]; Dari vs. RG2: ROR = 2.35; 95CI%[1.93, 2.85]), depression (n = 22; Dari vs. RG1: 2.13; [1.39, 3.25]; Dari vs. RG2: ROR = 2.31; 95CI%[1.45, 3.67]), and hangover (n = 20; Dari vs. RG1: ROR = 127.92; 95CI%[81.98, 199.62]; Dari vs. RG2: 3.38; [2.04, 5.61]) were considered as safety signals. These data provide valuable insights into the real-world safety profile of dari-dorexant, supporting the existence of safety signals related to nightmares, depression, and hang-over.

The impact of systemic vascular resistance (SVR) in hypertrophic (HCM) and amyloid cardio-myopathies has been seldom investigated. We studied pressure-strain loop derived myocardial work (MW) indices and SVR in patients with either sarcomere HCM or wild type transthyretin cardiac amyloidosis (ATTR), presented with heart failure and preserved left ventricular ejection fraction (HFpEF) at the outpatient cardiology units at Messina and Catania University Hospitals (Italy). Patients were in sinus rhythm and needed to have good transthoracic ultrasound imaging quality to undergo transthoracic strain-echocardiography. Other than conventional parameters, SVR and GWI (global work index) were measured. Based on cross-tabulation (a way to assess the ventricular-arterial coupling), the patients were then classified in 4 classes according to the cut-off values suggested by previous studies of 1,440 dyne/s/cm-5 for SVR (Stefadouros et al., 1973) and 1576 mm Hg% for GWI (Olsen et al., 2022). Sixty patients, 30 in each group, aged 61±16 years, 78% males, were studied. HCM were younger than ATTR patients and in a better clinical status (23% HCM vs 77% ATTR were NYHA class 3, p<0.001). Overall, 51 patients (85%) showed high SVR, of whom 21 were HCM (70%) and 30 ATTR (100%) (p<0.005). Both, SVR and GWI were impaired (the poorest class C) in 43% HCM patients (with greater left ventricular concentric hypertrophy) vs 93% of ATTR patients (in advanced NYHA class) (p<0.001). In conclusion, assessing SVR and GWI in HFpEF patients with HCM or ATTR can help clinicians to interpret the pathophysiological and clinical features of such complex diseases.

Introduction: Despite great advances in the treatment of oncological diseases, the development of medical technologies to prevent or reduce complications of therapy, in particular, those associated with surgery and the introduction of antibiotics remains relevant. The aim of the study: to evaluate the effectiveness of the use of autoprobiotics based on indigenous non-pathogenic strains of Enterococcus faecium and Enterococcus hirae in the complex therapy of colorectal cancer (CRC) in the early postoperative period. Materials and methods: A total of 36 patients diagnosed with CRC were enrolled in the study. The study group (Group A) comprised 24 CRC patients who received autoprobiotic therapy in the early postoperative period, while the control group (Group C) included 12 CRC patients without autoprobiotic therapy.Prior to surgery and between days 14-16 post-surgery, comprehensive evaluations were conducted on all patients, encompassing the following: stool and gastroenterological complains analysis. examination of the gut microbiota (bacteriological study, quantitative polymerase chain reaction, metagenome analysis), analysis of interleukins in serum. Results: The use of autoprobiotics led to decrease dyspeptic complaints after surgery, was associated with absence of postoperative complications, did not cause side effects, led to a decrease in the level of pro-inflammatory cytokines (IL-6 and IL-18) in the blood serum. The use of autoprobiotics led to positive changes in the structure of escherichia and enterococci populations, the elimination of Parvomonas micra, Fusobacterium nucleatum, decrease in the quantitative content of Clostridium perfringens, Akkermansia muciniphila. Metagenomic analysis (16S rRNA) revealed an increase in alpha diversity. Conclusion: The administration of autoprobiotics in the postoperative period is highly effective and safe in the comprehensive treatment of colorectal cancer patients. Future studies will allow the discovery of additional fine mechanisms of autoprobiotic therapy and its impact on the digestive, immune, endocrine and neural systems.

Water is a limited resource that needs to be properly managed and distributed to the ever-growing population of the world. Rapid urbanization and development have drastically increased the overall water demand worldwide. Ageing water distribution networks are vulnerable to deterioration and leakage, thereby causing an estimated annual loss of about 48 trillion liters of water. To address these issues, efficient and reliable leakage detection and management techniques are necessary. In this paper, the results of the experiments performed on a looped water distribution network in AnSeong, Korea are discussed. Transient-based techniques were used and physical data were collected for the detection and localization of leakages in the experimental water pipes. The results obtained from the experiments demonstrated the applicability of transient techniques for leak analysis in looped water distribution networks.

This article studies the morphological parameters of vegetative and generative organs of different age groups of Crataegus ambigua from four populations in Western Karatau (Mangistau region, Kazakhstan). The study examined four populations Pop 1 Sultan Epe, Pop 2 Karakozaiym, Pop 3 Emdikorgan, and Pop 4 Samal located in various gorges of western Karatau. Some phylogenetic inference methods were applied using six genetic markers atpF-atpH, ITS, matK, psbK-psbI, rbcL, and trnH-psbA. We also used a statistical analysis of the vegetative and generative organs of plants for three age groups of plants (virgin, young generative, and adult generative). According to the age structure, Samal populations have a high concentration of young generative plants - 42.3% and adult generative plants - 30.9%. Morphological analysis showed the significance of the parameters of the generative organs and separated the Samal population into a separate group according to the main PCoA coordinates. The results of the floristic analysis showed that the populations in the Samal have a high concentration of species diversity. The comparative dendrogram of UPGMA shows the informativeness of the use of genetic markers and the psbK-psbI region can be used to judge the difference between the fourth Samal population and the other three.

Objectives: To rate the effects of low molecular weight hyaluronic acid (LMWHA) solution and high concentration oxygen (HCO) through a specific medical device (Caress Flow©), compared to topical administration of hyaluronic acid (HA) alone on symptoms of mild and moderate stress and mixed urinary incontinence in women with genitourinary syndrome of menopause (GSM). Methods: A total of 68 postmenopausal women were enrolled (from October 2021 to September 2023). Patients were separated in two groups: one group used therapy with LMWHA solution and HCO combined and the second group used therapy with HA alone. Patient Global Impres-sion of Improvement (PGI-I) as the first outcome was used. As secondary outcomes International Consultation on Incontinence Questionnaire - short form (ICIQ-SF) questionnaire and Internation-al Quality of Life (IQoL) questionnaire were used. Results: Sixty-eight (68) women, 35 (51%) and 33 (49%), were treated with LMWHA solution and HCO combined and HA alone for 10 weeks, respectively. 28 (80%) versus 7 (20%) women reported an improvement (PGI-I score ≤3) of the symptoms in LMWHA solution and HCO com-bined group versus HA alone group. According to the ICIQ-SF, a statistically significant differ-ence was recorded after treatment between the two groups (median, 7 [5-11] vs 10 [8-11]; P = 0.03). According to the IQoL questionnaire, a statistically significantly lower median score was recorded in the LMWHA solution and HCO combined compared with the HA group, before (71 [IQR 55-81] vs 89 [IQR 67-94]; P < 0.01) and after (78 [IQR 65-86] vs 88 [IQR 72-99]; P = 0.04) treatment. Conclusions: LMWHA solution and HCO combined might improve the mild and moderate stress and mixed urinary incontinence in this set of women and that it is superior to HA therapy alone. However, these results need to be confirmed in further studies with a controlled design and a larger population.

Alhagi pseudalhagi in the arid zone of the Atyrau region and an analysis of their current state with an assessment of raw material reserves were studied. Botanical characteristics, ontogenetic spectrum, morphological indicators, productivity, areas of thickets and reserves of raw materials of above-ground organs were assessed. The structural parameters of these coenopopulations in the Zhangyr and Coneu Rivers valleys, the vicinity of Imankara Mountain, and the Taisoigan sands were studied. It was established that the species composition of the populations includes 63 species from 54 genera and 30 families. The most common species include 49 taxa, category II – 17 taxa, category III – 7 species, category IV–V – 2 species. The maximum similarity in species composition was noted between populations in the Zhangyr and Coneu Rivers valleys. The maximum morphometric indicators were observed among the population of the river valley. Coneu and the minima are located on the Taisoigan sands. Analysis of the age spectrum made it possible to determine that the populations in the Zhangyr and Coneu Rivers valleys are characterized as young, in the area of Imankara Mountain and on the Taisoigan sands - as stable and middle-aged.

Despite the recent availability of immune checkpoint inhibitors, not all patients affected by Non-Small Cell Lung Cancer (NSCLC) benefit from immunotherapy. The reason for this variability relies to a variety of factors which may allow the identification of novel biomarkers. Presently, a variety of biomarkers are under investigation, including the PD1/PDL1 axis, the tumor mutational burden, and the Microbiota. This latter is made by all bacteria and other microorganisms hosted in our body. The gut microbiota is the most represented and has been involved in different physiological and pathological events, including cancer. In this light, it appears that all conditions modifying gut microbiota can influence cancer, its treatment, and its treatment-related toxicities. The aim of this review is to analyze all conditions influencing the gut microbiota and, therefore, affecting response to immunotherapy, iRAEs and their management in NSCLC patients. The investigation of the landscape of these biological events can allow novel insights for optimal management of NSCLC immunotherapy.

Cognitive impairment affects 34-65% of People with Multiple Sclerosis (PwMS), significantly impacting their quality of life. Clinicians routinely address cognitive deficits with in-clinic neuro-behavioural interventions, but accessibility issues exist. Telerehabilitation is a promising solution that utilises digital tools for home-based cognitive remediation. This narrative review assessed the feasibility and efficacy of cognitive telerehabilitation in PwMS, identifying 13 relevant studies. Regarding the feasibility of cognitive telerehabilitation, evidence shows adherence rates are generally good, although, surprisingly, not all studies reported a measure of compliance with the cognitive training explored. Considering the efficacy of different rehabilitative techniques on cognitive performance of PwMS, findings are generally inconsistent, with only one study reporting consistently positive results. A range of methodological limitations are reported as potential factors contributing to the variability of results. Overcoming some of these issues will be key. Upcoming research is necessary to determine optimal intervention approaches, long-term effects of rehabilitation, and how to best integrate the use of telerehabilitation into routine clinical practice. By exploiting digital tools in the best way and addressing methodological concerns, home-based rehabilitation holds the potential for improving cognitive functions and enhancing the quality of life in PwMS.

Renal cell carcinoma (RCC) accounts for approximately 90-95% of all kidney cancers in adults, with the clear cell RCC (ccRCC) the most frequently identified subtype. RCC is known for its responsiveness to immunotherapy, making it an area of significant research interest. Immune checkpoint (IC) molecules, which regulate immune surveillance, are established therapeutic targets in RCC. The aim of this study was to analyze the influence of polymorphisms in genes HVEM and CD160 on susceptibility to ccRCC and patient overall survival (OS) with over a ten-year period of observation. We genotyped three HVEM single nucleotide polymorphisms (SNPs): rs1886730, rs2234167, and rs8725, and two CD160 SNPs: rs744877 and rs2231375, in 238 ccRCC patients and 521 controls. Our findings indicated that heterozygosity within rs2231375 and/or rs2234167 increases ccRCC risk. Furthermore, in women, heterozygosity within additional HVEM SNPs, rs8725 and rs1886730, is associated with an increased ccRCC risk. The presence of a minor allele for rs1886730, rs2234167, rs8725, and rs2231375 was also correlated with certain clinical features of the disease. Moreover, the rs1886730 SNP was found to be associated with patients' OS. In conclusion, our study highlights an association between HVEM and CD160 polymorphisms and the risk of developing ccRCC as well as patient’s OS.

Background. The possible interactions between anger and fear have not been widely explored in the psychological literature. Fear and anger are currently beginning to be studied by looking at their interrelationships, rather than seeing them as simply opposing emotions. Furthermore, there is a tendency to think that anger is more typical of men and fear of women. Our contribution proposes a particular perspective of affective neuroscience. The objectives of the study are: 1) To assess possible differences in affective systems, states, and traits of anger in relation to biological sex; 2) To assess correlations between ANGER, FEAR, and PANIC, state and trait anger in both a female and male sample; 3) To assess possible differences in basic affective systems in relation to different levels of ANGER, FEAR, and PANIC, state and trait anger, in sample of female and in sample of male. Methods. A non-clinical sample of 339 females and 99 males completed the ANPS 3.1 to assess basic affective states and the STAXI 2 to assess anger states and traits. Results. No significant differences were found for ANGER and FEAR scores and for state and trait scores between the male and female samples. Clear correlations emerged (p < .01) between FEAR. PANIC and FEAR in both the female and male samples. Among the differences that emerged in the affective systems, we emphasise that in the female group as FEAR increases, there are significant variations in systems of SEEKING, PLAY, and CARE. Furthermore, only in the female sample as PANIC increases, PLAY progressively decreases, and CARE shows an irregular trend. Discussion. Given the importance of the SEEKING and PLAY systems for well-being and gender equality the hypoactivation of these systems to increases in FEAR and PANIC highlights the need to monitor conditions that may trigger these affective systems.

This paper presents results from numerical and experimental investigation on Charpy tests in order to point out failure mechanisms and to evaluate new polymeric blends PP+PA6+EPDM. Charpy tests were done for initial velocity of the impactor of 0.96 m/s and its mass of 3.219 kg and these data were also introduced in the finite element model. The proposed model take into account the system of four balls, including support and the ring of fixing the three balls and it has a finer discretization of the impact area to highlight the mechanisms of failure and their development in time. The constitutive models for four materials (polypropylene with 1% Kritilen, two blends PP+PA6+EPDM and a blend PA6+EPDM) were derived from tensile tests. Running simulations for each constitutive model of material makes possible to differentiate the destruction mechanisms according to the material introduced in the simulation, including the initiation and the development of the crack(s), based on equivalent plastic strain at break (EPS) for each material. The validation of the model and the simulation results was done qualitatively, analysing the shape of broken surfaces and comparing them to SEM images and quantitatively by comparing the impact duration, energy absorbed by the sample, the value of maximum force during impact. The duration of the destruction of the specimen is longer than the actual one, explainable by the fact that the material model does not take into account the influence of the material deformation speed in Charpy test, the model being designed with the help of tests done at 0.016 m/s (1000 mm/min) (maximum strain rate for the tensile tests). Experimental results are encouraging for recommending the blends 20% PP+42% PA6+28% EPDM and 60% PA6+ 40%EPDM as materials for impact protection at low velocity (1m/s). Simulation results are closer to the experimental ones for the more brittle tested materials (with less content of PA6 and EPDM) and more distanced for the more ductile materials (with higher content of PA6 and EPDM).

Abstract A multiple number of studies provide evidence that vasopressin (AVP) and steroid hormones are frequently secreted together and closely cooperate in the regulation of blood pressure, metabolism, water-electrolyte balance, and behavior, securing thereby survival and comfort of life. Vasopressin interacts with hormones of the hypothalamo-pituitary-adrenal axis (HPA) at several levels through regulation of release of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone ACTH, and multiple steroid hormones, as well as through interactions with steroids in the target organs. The interactions are facilitated by positive and negative feedbacks occurring between specific components of the HPA axis with engagement of other regulatory molecules. Altogether AVP and HPA cooperate closely as a coordinated functional AVP-HPA system. It has been shown that cooperation between AVP and steroid hormones may be affected by the cellular stress combined with hypoxia, and by metabolic, cardiovascular and respiratory disorders, neurogenic stress and inflammation. Growing evidence indicates that central and peripheral interactions of AVP and steroid hormones are reprogrammed in cardiovascular diseases and that the rearrangements play either beneficial or harmful effects. The present review highlights specific mechanisms of interactions of AVP and steroids at cellular and systemic levels and analyses consequences of inappropriate cooperation between various components of the AVP-HPA system for the regulation of the cardiovascular system and energy balance in cardiovascular and metabolic diseases.

The ovary is the major determinant of female reproductive health. Ovarian functions are mainly related to the primordial follicle pool, which is gradually loss with aging. Ovarian aging and reproductive dysfunctions share oxidative stress as common underlying mechanism. ROS signaling is essential for normal ovarian processes yet can contribute to various ovarian disorders when disrupted. Therefore, balance in the redox system is crucial for proper ovarian functions. In the present study, by focusing on mRNAs and ncRNAs described in the ovary and taking into account only validated ncRNA interactions, we built up an ovarian antioxidant ceRNA network, namely OvAnOx ceRNA, composed of 5 mRNAs (SOD1, SOD2, CAT, PRDX3, GR), 10 miRNAs and 5 lncRNAs (XIST, FGD5-AS1, MALAT1, NEAT1, SNHG1). Our bioinformatic analysis indicated that the components of the OvAnOx ceRNA not only contribute to antioxidant defence, but are also involved in other ovarian functions. Indeed, antioxidant enzymes encoded by mRNA of OvAnOx ceRNA operate within a regulatory network that impacts ovarian reserve, follicle dynamics, and oocyte maturation in normal and pathological conditions. The OvAnOx ceRNA represents a promising tool to unravel the complex dialogue between redox potential and ovarian signalling pathways involved in reproductive health, aging and diseases.

Adolescence is a central phase for the development of a person’s identity involving complex multidimensional changes and increasing vulnerability to distress. The aim of this study was to investigate the psychological well-being of adolescent students in Brescia (Northern Italy), two years after the beginning of the Covid-19 pandemic. An online survey investigated the extent and the reasons reported by high school students for their emotional distress (ED), also considering other factors such as physical activity, diet, sleep and smartphone overuse. The main reasons for ED were classified through a qualitative analysis of the freetext answers. 1686 students agreed to participate, 50% showed a presence of ED. According to a multiple logistic analysis, the main factors associated to ED were female gender (AdjOR 2.3, p<0.0001), age (AdjOR 1.6, p<0.0001), sleep duration <8 hours (AdjOR 1.5, p=0.0003), anxiety perception (AdjOR 3.4, p<0.0001), and certain eating behaviors, e.g. comfort food consumption (AdjOR 2.0, p<0.0001). According to free-text answers, the main reasons for ED were: “school pressure”, “ relationships with family and peers”, “negative emotional states” and “the pandemic”. The results show a high level of ED among adolescents and the reported reasons may help to better address their psychological needs after the pandemic.

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

Background: Cardiac development is a complex developmental process. The early cardiac straight tube is composed of an external myocardial layer and an internal endocardial lining. Soon after rightward looping, the embryonic heart becomes externally covered by a new epithelial lining, the embryonic epicardium. A subset of these embryonic epicardial cells migrate and colonize the embryonic myocardium, contributing to distinct cell types. In recent years, our understanding of the molecular mechanisms that govern proepicardium and embryonic epicardium formation has greatly increased. We have recently witnessed a novel layer of complexity governing gene regulation with the discovery of non-coding RNAs. Our laboratory recently identified three distinct lncRNAs, adjacent to the Wt1, Bmp4 and Fgf8 chicken gene loci, with enhanced expression in the proepicardium that are distinctly regulated by Bmp, Fgf and thymosin 4, providing support of their plausible implication in epicardial formation. Methods: Expression of lncRNAs was analyzed in different chicken and mouse tissues as well as their subcellular distribution in chicken proepicardial, epicardial, ventricle explants and in different murine cardiac cell types. lncRNA transcriptional regulation was analyzed by using siRNAs and expression vectors of different transcription factors in chicken and mouse. Antisense oligonucleotides were used to inhibit Gm14014 expression. Cardiac injury was induced ex vivo in mouse ventricle explants by cryoinjury. Furthermore, RT-qPCR, immunocytochemistry, RNA pulldown, Western blot, viability and cell migration assays were conducted to investigate the biological function of Wt1_76127 and Gm14014. Results: We demonstrated that Wt1_76127 in chicken and its evolutionarily conserved homologue Gm14014 in mice are widely distributed in different embryonic and adult tissues and distinctly regulated by cardiac enriched transcription factors, particularly Mef2c and Nkx2.5. Gm14014 is distinctly regulated in mouse ventricular cryoinjury ex vivo models, displaying a negative correlation with epicardial and epithelial to mesenchymal transition markers. Furthermore, silencing assays demonstrated that mouse Gm14014, but not chicken Wt1_76127, is essential for epicardial, but not endocardial or myocardial cell migration. Such process is governed by partnering with Myl9, promoting cytoskeletal remodeling. Conclusion: Our data evidence that Gm14014 plays a pivotal role in epicardial cell migration essential for heart regeneration.

Uterine pathologies pose a challenge to women’s health on a global scale. Despite extensive research, the causes and origin of some of these common disorders are not well defined yet. This study presents a comprehensive analysis of transcriptome data from diverse datasets encompassing relevant uterine pathologies such as endometriosis, endometrial cancer and uterine leiomyomas. Leveraging the Comparative Analysis of Shapley values (CASh) technique, we demonstrate its efficacy in improving the outcomes of classical differential expression analysis on transcriptomic data derived from microarray experiments. CASh integrates the Microarray game algorithm with Bootstrap resampling, offering a robust statistical framework to mitigate the impact of potential outliers in the expression data. Our findings unveil novel insights into the molecular signatures underlying these gynecological disorders, highlighting CASh as a valuable tool for enhancing the precision of transcriptomics analyses in complex biological contexts. This research contributes to a deeper understanding of gene expression patterns and potential biomarkers associated with these pathologies, offering implications for future diagnostic and therapeutic strategies.

This paper details the comprehensive activities conducted in a laboratory setting to assess the Structural Health Monitoring (SHM) of prefabricated building envelopes. Aimed at enhancing the structural evaluation of buildings, the focus of this research lies in employing nondestructive sensors for SHM with the objective to advance in the understanding and assessment of facade conditions. The paper outlines the methodologies employed, starting with a modal analysis to define the structural vibration's modal frequency. Subsequently, tests were defined and executed to validate building envelope compliance in case of stress typical of high-rise building. Throughout these tests, continuous monitoring of the façade was conducted using both conventional (accelerometers, extensimeter washers) and non-conventional sensors (Fiber Optic Sensing) The gathered data underwent thorough processing and analysis to provide an overall perspective on the structure's behavior during the stress test. The investigation aimed to identify whether specific physical phenomena correlate with distinct signals and to evaluate if continuous façade monitoring over the building's lifespan aids in preventing potential structural damage. Moreover, two modal analyses were conducted to compare final data and frequencies with earlier data, enabling the detection of any structural alterations. The results from compliance testing and structural analysis yielded noteworthy insights contributing to the evolving field of structural health monitoring, offering valuable findings that advance our ability to proactively manage and maintain the integrity of building structures.

The nuclear hormone family of receptors regulates gene expression. The androgen receptor (AR) shuttles upon ligand binding and homodimerization from the cytosol into the nucleus to activate gene expression. Thyroid hormone receptors(TR), retinoic acid receptors (RAR), and the vitamin D receptor (VDR) are present in the nucleus bound to chromatin as a heterodimer with the retinoid X receptors (RXR) and repress gene expression. Ligand binding leads to transcription activation. The hormonal ligands for these receptors play crucial roles to ensure the proper conduct of very many tissues and exert effects on prostate cancer (PCa) cells. Androgens support PCa proliferation and deprivation alone or with chemotherapy is the standard therapy for PCa. RAR activation and 3,5,3'-triiodo-L-thyronine (T3) stimulation of TR support the growth of PCa cells. Ligand stimulation of VDR drives growth arrest, differentiation, and apoptosis of PCa cells. Often these receptors are explored as separate avenues to find treatments for PCa and other cancers. However, there is accumulating evidence to support receptor interactions and crosstalk of regulatory events whereby a better understanding might lead to new combinatorial treatments.

A low cost, scalable and robust process has been proposed as innovative method for coating solar mirrors with a self-cleaning, transparent in the full solar range and versatile material based on auxetic aluminium nitrides, previously obtained on the laboratory scale. This work presents the scaling-up of fabrication process from laboratory to prototypal scale and pre-liminary results of outdoor self-cleaning solar mirror prototypes testing in the demonstrative CSP plant ENEASHIP located in Casaccia (Rome) ENEA research centre. Prototypes 50x40cm have shown stability in external conditions: no degradation occurs during the test campaign. Their washing restores the initial reflectance affected by soiling and the self-cleaning performance allows the utilization of a reduced quantity of water for cleaning operations with respect to uncoated glass of back surface mirrors. A similar self-cleaning AlN coating could be utilized on other solar components affected by soiling, such as glass envelopes of heat collecting elements, PV panels and everywhere are required self-cleaning performance combined to optical ones.

The performance of the presurgical test (preSurg) for temporal lobe epilepsy (TLE) was evaluated via video-electroencephalography (VEEG), electroencephalography (EEG), 99mTc-HmPAO single-photon emission tomography (SPECT) and 1.5 T magnetic resonance imaging (MRI) in a group of 112 men (37.0 ± 1.1 years) and 106 women (39.7 ± 1.1 years) operated on for TLE. The epileptic zone (EZ) was adequately identified to determine whether the patient reached an Engel I grade (EI) at least one year postop. Accuracy was evaluated by the coefficient α, ranging from 3 (when result = EZ) to 2 (result in the same hemisphere as the EZ), 1 (noninformative result) or 0 (EZ in the contralateral hemisphere). The simplicity of diagnosis was defined as the number of preSurg surgeries needed to identify the EZ. EI was obtained in 85.8% of patients even though 42.2% of patients had noninformative MRI results. For preSurg α was (mean ± SEM) = VEEG (2.83 ± 0.04) &gt; MRI (2.14 ± 0.08) &gt; EEG (1.87 ± 0.09) &gt; SPECT (1.71 ± 0.09). The accuracy (combination of sensitivity and specificity) was calculated as follows: VEEG (0.797) &gt; MRI (0.518) &gt; EEG (0.446) &gt; SPECT (0.360). The likelihood positive ratio was greater, and the likelihood negative ratio was lower for VEEG. The most relevant factor for the regression model was VEEG (3.106) &gt; MRI (2.558) &gt; EEG (1.905), and the factors were not significantly related to SPECT. EZs in EI patients with low simplicity were identified mainly by VEEG. A very good postoperative outcome can be obtained even in TLE patients with no lesions on MRI. The VEEG is the most reliable preSurg test and may be the only reliable test for patients with very low simplicity (i.e., difficult).single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

Crop rotation diversification using legumes has been advocated as one of the solutions to improve the resilience of the crop system to various environmental stresses and the use of nitrogen resources. However, when forage legumes or grass-legumes are ploughed, there is a high risk of nitrate leaching, especially in sandy soils. The aim of the study was to determine the effect strip tillage intercropping management on soil mineral nitrogen (SMN), water-extractable organic carbon (WEOC) content and winter wheat (WW, Triticum aestivum L.) grain yield compared to forage legume and WW monocropping with conventional tillage. In intercropping was used winter wheat - black medick (Medicago lupulina L.) WW+BM, winter wheat - white clover (Trifolium repens L.) WW+WC, and winter wheat - Egyptian clover (Trifolium alexandrinum L.) WW+EC. Research was repeated in two experiments. The results showed that after strip tillage and WW sowing less or similar SMN content cud be detected, as in conventional tillage and WW + forage legumes intercropping. WW grain yield in intercrops decreased, compared to the grasses monocultures that were ploughed before WW sowing. The highest amount of WEOC was in intercropping soil growing WW+WC or in all fields (except WW+EC) after applying strip tillage. During the research period, the amounts of mobile humic substances (HSs) and mobile humic acids (HAs) changed analogously. Their content increased substantially in fields with WC and EC, regardless of whether the grasses were ploughed or grown with WW.

Bosentan, an endothelin-receptor antagonist (ERA), has potential anti-atherosclerotic properties. We investigated the complementary effects of bosentan and atorvastatin on the progression and composition of the atherosclerotic lesions in diabetic mice. Forty-eight male apoE-/- mice were fed high-fat diet (HFD) for 14 weeks. At week 8, diabetes was induced with streptozotocin and mice were randomized into 4 groups: 1) Control/COG: no intervention. 2) ΒΟG: bosentan 100 mg/kg/day per os. 3) ATG: atorvastatin 20mg/kg/day per os). 4) BO+ATG: Combined administration of bosentan and atorvastatin. The intra-plaque contents of collagen, elastin, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-a (TNF-a), matrix-metalloproteinases (MMP-2,-3,-9), and TIMP-1 concentrations were determined. The percentage of lumen stenosis significantly decreased across all treated groups: BOG: 19.5±2.2%, ATG: 12.8±4.8%, BO+ATG: 9.1±2.7% compared to controls (24.6±4.8%, p&lt;0.001). Both atorvastatin and bosentan significantly increased collagen content and fibrous cap thickness versus COG (p&lt;0.01). All intervention groups reduced the relative intra-plaque concentrations of MCP-1, MMP-3,-9, and increased TIMP-1 compared to COG (p&lt;0.001). Importantly, bosentan showed modest but additive to atorvastatin effects on the latter parameters compared COG (p&lt;0.05). Bosentan treatment in diabetic, atherosclerotic apoE-/- mice delayed the atherosclerosis progression and enhanced plaques’ stability, showing modest but complementary effects with atorvastatin, which are promising in atherosclerotic cardiovascular diseases.

Antimicrobial peptides (AMPs) are promising tools for combating microbial resistance. However, their therapeutic potential is hindered by two intrinsic drawbacks – low target affinity and poor in vivo stability. Macrocyclization, a process that improves the pharmacological properties and bioactivity of peptides, can address these limitations. As a result, macrocyclic peptides represent attractive drug candidates. Moreover, many drugs are macrocycles that originated from natural product scaffolds, suggesting that nature offers solutions to the challenges faced by AMPs. In this review, we explore natural cyclic peptides from the DBAASP database. DBAASP is a comprehensive repository of data on antimicrobial/cytotoxic activities and structures of peptides. We analyze the data on small (≤25 AA) ribosomal and non-ribosomal cyclic peptides from DBAASP according to their amino acid composition, bonds used for cyclization, targets they act on, and mechanisms of action. This analysis will enhance our understanding of the small cyclic peptides that nature has provided to defend living organisms.

In this paper, we study the asymptotic behavior of the sequential empirical process and the sequential empirical copula process, both constructed from residuals of multivariate stochastic volatility models. Applications for the detection of structural changes and specification tests of the distribution of innovations are discussed. It is also shown that if the stochastic volatility matrices are diagonal, which is the case if the univariate time series are estimated separately instead of being jointly estimated, then the empirical copula process behaves as if the innovations were observed; a remarkable property. As a by-product, one also obtains the asymptotic behavior of rank-based measures of dependence applied to residuals of these time series models.

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer characterized by two etiologies: the first one, observed in most cases, is attributed to Merkel cell polyomavirus (MCPyV), a DNA tumor virus, while the second one is due to ultraviolet (UV) radiation exposure. Currently, there are limited diagnostic, prognostic, and therapeutic biomarkers available for MCC. MicroRNAs (miRNAs) are small RNA molecules that do not code for proteins but regulate various cellular processes, including cell cycle progression, proliferation, differentiation, and apoptosis. The dysregulation of miRNAs has been associated with a wide range of cancers since they can act as either tumor suppressors or oncogenes. This paper aims to collect, summarize and re-organize the recent discoveries concerning miRNAs, whose dysregulation in the pathogenesis and progression of MCC is slowly emerging. Furthermore, the potential clinical applications of miRNAs as diagnostic biomarkers, possible differentiation between MCPyV-related and unrelated MCC, predictors of response to therapy and prognostics are also discussed. From this review, it emerges that miRNAs may have, in the near future, the potential to become clinically significant in improving the diagnostic accuracy, prognostic evaluation, and therapeutic options of MCCs. Finally, the new perspectives on the poorly explored field of artificial intelligence in MCC are provided.

The increasing prevalence of Metabolic Syndrome (MetS), a serious condition associated with elevated risks of cardiovascular diseases, stroke, and type 2 diabetes, underscores the urgent need for effective diagnostic tools. This research carefully examines the effectiveness of 16 diverse machine learning (ML) models in predicting MetS, a multifaceted health condition linked to increased risks of heart disease and other serious health complications. Utilizing a comprehensive, unpublished dataset of imbalanced blood test results, spanning from 2017 to 2022, from the Laboratory Information System of the General Hospital of Amfissa, Greece, our study embarks on a novel approach to enhance MetS diagnosis. By harnessing the power of advanced ML techniques, we aim to predict MetS with greater accuracy using non-invasive blood test data, thereby reducing the reliance on more invasive diagnostic methods. Central to our methodology is the application of the Borda count method, an innovative technique employed to refine the dataset. This process prioritizes the most relevant variables, as determined by the performance of the leading ML models, ensuring a more focused and effective analysis. Our selection of models, encompassing a wide array of ML techniques, allows for a comprehensive comparison of their individual predictive capabilities in identifying MetS. This study not only illuminates the unique strengths of each ML model in predicting MetS but also reveals the expansive potential of these methods in the broader landscape of health diagnostics. The insights gleaned from our analysis are pivotal in shaping more efficient strategies for the management and prevention of Metabolic Syndrome, thereby addressing a significant concern in public health.

Due to the genotype-dependent effects of water deficit (WD) on coffee physiology, climate change raises the risk of coffee yield. The aim of the study was to assess the effect of WD on physiological and growth traits in arabica coffee (Coffea arabica L.). Water status, photosynthetic response to in-tercellular concentration of CO2 (A/Ci curves) and growth parameters were evaluated in seedlings of four genotypes (Catimor ECU 02, Cavimor ECU, red Caturra and Sarchimor 4260). Most of the physiological traits evaluated differed significantly among genotypes. Between control and WD plants, there were significant differences in A/Ci parameters, showing a wide range of values for photosynthetic rate, stomatal conductance, and water use efficiency, with decreases ranging from 4 to 74%. Maximum rate of carboxylation by RuBisCO, maximum electron transport rate through photosystem II, and triose phosphate utilization rate were all strongly reduced by WD 61 % (red Caturra and Sarchimor 4260), followed by Cavimor ECU (35 %) and 24 % in Catimor ECU 02. Differences in response to WD among genotypes suggest possible genotypic differences in toler-ance. The results indicated that Catimor ECU 02 and Cavimor ECU were less sensitive to WD, while red Caturra and Sarchimor 4260 were the most susceptible.

To secure logic circuits against the illegal copying the insertion of the so-called key bit inputs using XOR/XNOR gates has been proposed in . The inserted gates modify (lock) the behavior of the original circuit and only the correct choice of the secret key bits guarantees the equivalent behaviour of the locked circuit to the original circuit. To break this kind of security, i.e. to find the secret key bits, there was a SAT solver based attack proposed in . The aim of this work is to experimentally verify this attack on several locked circuits with various number of primary inputs and outputs and with various number of gates. Except for the random placement of the key gates we evaluate also the positioning with chaining elimination. The obtained and presented results show that we were able to unlock 10 of 11 circuits within few minutes on a common PC.

Idiopathic pulmonary fibrosis [IPF] is a chronic progressive disease characterised by the accumulation of scar tissue in the lung parenchyma. It primarily occurs in middle-aged and elderly adults and results in significant morbidity and mortality worldwide. The disease occurs due to repetitive lung epithelial injury, subsequent fibroblast activation and myofibroblast differentiation, resulting in excessive extracellular matrix deposition. This leads to scar formation and subsequent loss of lung function. Current treatment options for patients with IPF include the two anti-fibrotic drugs, pirfenidone and nintedanib, which can slow disease progression; however, there are currently no known cures for the disease. As such, novel methods and drug targets are warranted. In this review, we provide an up-to-date account of the importance of specific cytokines and the potential role of regulatory immune cells. We discuss their role in the pathogenesis of IPF and address some of the key gaps in knowledge.

Japanese plum tree (Prunus salicina Lindl.) is mainly cultivated in temperate areas of China and some European countries. Certain amounts of wood (from pruning works) are generated every year from this crop of worldwide commercial significance. The main objective of this work was to value this agricultural woody residue, for which the chemical composition of pruning wood extracts from six Japanese plum cultivars was investigated, and the antiproliferative activity of extracts and pure phenolics present in those extracts was measured. For the chemical characterization, total phenolic content and DPPH radical-scavenging assays and HPLC‒DAD/ESI‒MS analyses were performed, the procyanidin (‒)-ent-epicatechin-(2α→O→7,4α→8)-epicatechin (5) and the propelargonidin (+)-epiafzelechin-(2β→O→7,4β→8)-epicatechin (7) being the major components of the wood extracts. Some quantitative differences were found among plum cultivars, and the content of proanthocyanidins ranged from 1.50 (cv. ‘Fortune’) to 4.44 (cv. ‘Showtime’) mg/g of dry wood. Regarding the antitumoral activiy, eight wood extracts and four phenolic compounds were evaluated in MCF-7 cells after 48 h of induction, showing the wood extract from cv. ‘Songold’ and (‒)-annphenone (3) the best antiproliferative activity (IC50: 424 ppm and 405 ppm, respectively).

Curcumin, found in the rhizome of turmeric, has extensive therapeutic promises via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown curcumin to be an effective treatment for multiple cancers. These effects are drived by curcumin's ability to induce G2/M cell cycle arrest, induction of autophagy, activation of apoptotic pathways, disruption of molecular signaling, inhibition of invasion and metastasis, and by increasing the efficacy of existing chemotherapeutics. Here we focused on the hormetic behaviour of curcumin. Frequently, low doses of toxins and other stressors not only are harmless but also activate an adaptive stress whereas high dose activates acute responses like autophagy and cell death. This phenomenon is referred to as hormesis. Many molecules that cause cell death elicite an initial autophagic step that is a cytoprotective mechanism relying on elimination of dysfunctional structures intracellular, notably by mitophagy. This phenomenon is considered as a primarily protective mechanism against stressors. At higher doses, cells undergo mitochondrial outer membrane permeabilization due to calcium release from the endoplasmic reticulum and die. Herein, we address the complex crosstalk between the induced mitochondrial biogenesis, mitochondrial destabilization accompanied by mitophagy and cell death that can also be at play.

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent world-wide. It progresses from simple steatosis to non-alcoholic steatohepatitis (NASH). Fibrosis is often present during NAFLD progression; however, factors determining which subjects develop NASH or fibrosis are unclear. Insulin-like growth factor binding proteins (IGFBP) is a family of secreted proteins involved in senescence and scarring mainly synthetized in the liver. Here we aimed to study the association of IGFBP and its induced senescence with the progression of NAFLD and liver fibrosis. Materials and Methods: 16 weeks old male C57BL/6 mice weighing 23 ± 3 g were fed either Methionine-Choline Deficient or control diet for 2, 8 or 12 weeks. Blood and liver samples were collected; histological assessment of NAFLD and fibrosis was performed. Fat contents were measured. Cellular senescence was evaluated in the liver. IGFBP levels were assessed in liver and serum. Data was expressed as Mean ± SD and analyzed by one-way ANOVA followed Tukey’s test. Lineal regression models were applied for NAFLD and fibrosis progression. p

Background: high-altitude work exposes individuals to reduced oxygen levels, imposing physi-ological adaptations. These conditions can induce alterations in the cardiovascular system, po-tentially exacerbating pre-existing health issues and impacting overall well-being of workers in such environments. This study has investigated the cardiovascular challenges for the high-altitude worker on Etna volcano. Methods: Through an observational study, ten healthy, non-smoking male participants underwent cardiovascular and pulmonary function tests at alti-tudes below 500m and above 3000m, simulating work conditions on the volcano. Results: signif-icant findings include elevated systemic blood pressure and heart rate, indicating an increased cardiovascular workload necessary for adaptation to hypoxia. Conclusions: the study highlights the importance of acclimatization to high altitude for minimizing cardiovascular risks among workers. It calls for the development of safety protocols, underlining the critical role of preven-tative measures and specific safety protocols for high-altitude workers.

: Tunnel instability and lining integrity are intimately tied to the creep properties of the surrounding rock. The acquisition of rock mass creep parameters is critical in ascertaining the appropriate timing for lining construction. Nevertheless, creep tests on rock specimens conducted in a controlled setting cannot be straightforwardly extrapolated to rock mass creep analysis. This study performs laboratory-based creep tests on mudstone samples and establishes the corresponding creep constitutive model. Integration of a Mohr-Coulomb element with the Burgers model in series serves to characterise the yield creep behaviour of the rock mass. Additionally, the research outlines a series of 100 orthogonal experiments utilising randomised creep parameters, and formulates a GA-BP neural network inversion model. Employing long-term deformation measurements from the crown and sidewalls of the project site, this study deduces the creep parameters of the mudstone in the investigated tunnel section and examines the prolonged deformation traits of the surrounding rock. Drawing on the deformation traits of the surrounding rock and the forces impacting the primary support and lining structures, this paper evaluates the earliest and latest viable lining casting periods and pinpoints an optimal timing interval for lining implementation. The methodologies employed herein can serve as a benchmark for analogous endeavors internationally.

Cancer cells require substantial amounts of energy and substrates for their metabolic hyperactivity, enabling the synthesis of new cells at the expense of healthy ones. Preliminary in vitro data suggest that a mix of free essential amino acids (EAA-mix) can promote cancer cell apoptosis by enhancing autophagy. This study aimed to confirm, both in vitro and in vivo, whether EAA intake could influence the development of colon cancer in mice. We investigated changes in cancer proliferation in CT26 cells treated with EAA-mix, and in mice fed with EAA rich modified diets (EAARD) as compared to those on a standard laboratory diet (StD). CT26 cells were injected subcutaneously (s.c.) or intraperitoneally (i.p.). After 21 days, tumors were removed and measured. In vitro data corroborated that EAA-mix impairs cancer growth by inducing autophagy and apoptosis. In vivo data revealed that mice on StD developed significantly larger (s.c.) and more numerous (i.p.) cancers than those on EAARD. EAA administration appears to influence cancer cell survival with notable anti-proliferative properties.

Transcatheter Aortic Valve Implantation (TAVI) now represents the mainstay in the treatment of severe aortic stenosis. Owing to its exceptional procedural efficacy and safety, TAVI has been extended to include patients at lower surgical risk, thus now encompassing a diverse patient population receiving this treatment. Yet, long-term outcomes also depend on optimal medical therapy for secondary vascular prevention, with antithrombotic therapy serving as a cornerstone. Leveraging data from multiple randomized controlled trials, current guidelines generally recommend single antithrombotic therapy, with either single antiplatelet therapy (SAPT) or oral anticoagulation (OAC) alone in those patients without, or with atrial fibrillation respectively. Yet, individualization of this pattern, as well as specific case uses, may be needed based on individual-patient characteristics and concurrent procedures. This review aims to discuss the evidence supporting antithrombotic treatments in patients treated with TAVI, indications for a standardized treatment, as well as specific considerations for an individualized approach to treatment.

Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSA/MAA) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies, may be underestimated. This study analyzed adult PH patients without pre-existing IIM for MSA/MAA prevalence using a line-blot assay. We compared PH patients with and without ILD signs to a cohort clinically suspected of IIM/ILD (n=558). Our PH cohort (n=121) showed a significantly higher prevalence of overall weak positive MSA/MAAs and positive overlap syndrome-associated MAAs than the suspected IIM/ILD group (p

We recently demonstrated the effectiveness of long-term treatment with rifaximin and the probiotic VSL#3 at improving urogenital and gastrointestinal symptoms in patients with both chronic inflammatory prostatitis (IIIa prostatitis) and diarrhea-predominant irritable bowel syndrome (IBS-D), relative to patients with IBS-D alone. Because low-grade inflammation of the intestine and prostate may be one of the reasons for co-developing both IIIa prostatitis and IBS-D, we designed the present study to once again evaluate the efficacy of combined rifaximin and VSL#3 treatment in patients affected by IIIa prostatitis plus IBS-D, but we also measured seminal plasma pro-inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines before and after treatment. We consecutively enrolled 124 patients with IIIa prostatitis and IBS-D (diagnosed using the Rome III criteria). Patients were randomized into two groups: group A (n=64) was treated with rifaximin (seven days per month for three months) followed by VSL#3, and group B (n=60) was treated with a placebo. At the beginning of the study and after three months of treatment, all patients completed NIH-CPSI and IBS-SSS questionnaires to score the severity of their urogenital and gastrointestinal symptoms, and we measured seminal plasma levels of IL-6 and IL-10 using ELISA. We defined patients who improved following the treatment as those with a ≥6-point reduction in their NIH-CPSI score or ≥50-point reduction in their IBS-SSS score. By the end of the intervention, 68.7% and 62.5% of patients from group A reported improved NIH-CPSI and IBS-SSS scores, respectively, compared to only 3.3% and 5% of the placebo group. Group A patients also had significantly lower mean seminal plasma levels of IL-6 (11.3 vs 32.4 pg/mL) and significantly higher mean levels of IL-10 (7.9 vs 4.4 pg/mL) relative to baseline, whereas levels of IL-6 and Il-10 did not change in the placebo group. The co-occurrence of two clinical phenotypes (IBS-D plus IIIa prostatitis) result in increased intestinal inflammation and altered immune activation, both of which can be balanced by treatment with rifaximin and VSL#3.

To address the insufficient mechanical properties of calcined phosphogypsum, this research aims to investigate the utilization of basalt fiber and calcium carbonate whiskers as reinforcing agents. The study examines their impact on the flexural and compressive strength, toughness, water resistance, and tensile strength of calcined phosphogypsum. In the individual tests, basalt fibers with different lengths (3 mm, 6 mm, 9 mm, and 18 mm) were added at dosages of 0%, 0.5%, 1.0%, and 1.5% respectively. The findings demonstrate that basalt fiber effectively enhances the flexural and compressive strength, toughness, and tensile strength of calcined phosphogypsum, albeit potentially compromising water resistance. Among the various fiber lengths, the 6 mm fibers exhibit the most advantageous influence on the performance of calcined phosphogypsum. A subsequent test was conducted to investigate the impact of cross-scale fibers on the properties of calcined phosphogypsum by mixing 6 mm basalt fibers and calcium carbonate whiskers. The results illustrate that calcium carbonate whisker refines the pores, thereby improving the flexural strength and toughness of calcined phosphogypsum. Furthermore, it compensates for the water resistance limitations associated with the sole utilization of basalt fiber while further augmenting the tensile strength and strain capacity. However, it should be noted that increasing the dosage of both calcium carbonate whiskers and basalt fibers concurrently leads to increased porosity of phosphogypsum and reduced compressive strength.

Hemophagocytic lymphohistiocytosis (HLH) is a serious haematologic condition that can be re-lated to various diseases, including tuberculosis (TB). The patient is a previously healthy 26-years-old man, originally from Western Africa, admitted to hospital for fever and weight loss. Given the results of computed tomography (CT) scan, ocular examination and microbiologic tests, a miliary TB with pulmonary, lymph nodal and ocular involvement was diagnosed. Following introduction of antitubercular treatment (ATT) an increase in inflammation indexes and severe pancytopenia were observed; at this point the patient presented six of eight diagnostic criteria for HLH and the diagnosis of HLH secondary to TB was raised. Therefore, HLH treatment with high dose of dexamethasone was started with a good clinical response. We performed a literature re-view of TB-related HLH, which shows a high mortality rate; ATT is necessary to ensure patient survival to remove the antigenic driver. Our patients developed HLH after initiation of ATT as a paradoxical reaction, that may be linked to the release of antigens due to the bactericidal effect of ATT.

JAK2 V617F is a somatic mutation associated with myeloproliferative neoplasm (MPN): polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). In MPNs this mutation is associated with the germline GGCC (46/1) haplotype. Most studies consider the association of the JAK2 haplotypeGGCC_46/1 with some MPNs clinical parameters but no one analyzed the association between JAK2 haplotypeGGCC_46/1 and the onset of onco-drug resistance. Thus, we assessed for JAK2 46/1 haplotype correlation with therapy response in JAK2 V617F positive patients. Patients with MPN, selected by the Hematology Laboratory of “V. Fazzi” Hospital (LE), were analyzed with RLFP-PCR assay with rs10974944 SNP. Most of them had PV (63%) or PMF (61%). Among patients that developed onco-drug resistance, 58% had C/G genotype and only 11% had the G/G allele. No correlation between onco-drug resistance and JAK2 haplotype 46/1 variants emerged. Nevertheless, we observed that G/G allele seems to be related to MPNs evolution to myelofibrosis and to the development of onco-drug resistance clinical parameters (p-value= 0.002449; odd ratio of 3.701209). Thus, although other analyses are required, due to the narrow cardinality of sample, our findings suggest how the G/G allele could be useful for MPNs diagnosis and for the prediction of the disease outcome.

Vibrio parahaemolyticus is an important foodborne bacterium that causes severe gastroenteritis following the consumption of contaminated seafood. To identify V. parahaemolyticus and determine its pathogenicity, the U.S. Food and Drug Administration (FDA)’s Bacteriological Analytical Manual (BAM) recommends a multiplex polymerase chain reaction (PCR) protocol to simultaneously detect the species-specific thermolabile hemolysin (tlh) gene and the pathogenic thermostable-related hemolysin (trh) and thermostable-direct hemolysin (tdh) genes. However, this assay has shown two limitations: difficulty in separating the amplicons of the trh (486 bp) and tlh (450 bp) genes due to their similar sizes, and the weaker band exhibited by the tdh gene amplicon (270 bp). The present study aimed to improve the BAM’s multiplex PCR assay by separating the three amplicons with similar intensity. A new primer set was applied for the tlh gene (369 bp) alongside the existing primers for the trh and tdh genes. The amplicons for the three genes were effectively separated by electrophoresis on a 2% tris-borate-EDTA (TBE) agarose gel within 45 minutes. Primer concentrations of 0.2 µM for trh, 0.2 µM for tlh, and 0.4 µM for tdh produced a significant amount of amplicons among various combinations of primer concentrations with 35 PCR cycles (P &lt; 0.05). This assay exhibited a detection limit of 10 pg of bacterial DNA, demonstrating its high sensitivity. It did not display amplicons from nine Vibrio strains known to be human pathogens or from 18 well-documented foodborne pathogens. Therefore, the present multiplex PCR protocol could help overcome the limitations of existing assays and provide a more reliable method for detecting the three genes of V. parahaemolyticus.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder characterized by the development and progression of multiple renal cysts, leading to progressive renal function decline. To date, the only approved treatment for this condition is able to slow down the loss of annual renal function, without stopping the disease progression. Furthermore, this therapy is approved only for patients with rapid disease progression and its compliance is problematic because of the impact of this drug on quality of life. The recent literature suggests that cystic cells are subject to metabolic dysregulation in the glucose pathway (Warburg Effect). This finding paved the way for new lines of research targeting potential therapeutic interventions for ADPKD. In particular, this review highlights the latest studies on the use of ketosis, through ketogenic dietary interventions (daily calorie restriction, intermittent fasting, time-restricted feeding, and ketogenic diets), as a potential strategy for patients with ADPKD, and the possible involvement of microbiota in the ketogenic interventions’ effect.

Aim: The aim of this study was to investigate if tests used to assess core stability could be used to determine success in physiological tests applied to assess dynamic balance and agility for a young active population. Methods: Pearson's r correlation coefficient was used to assess the relationship between the core stability tests and the dynamic balance and agility tests. Evaluation of the tests was established using Cronbach's coefficient of variance as part of intra-rater reliability tests. An analysis of 18 active college aged students was conducted (males: n= 13, females: n= 5). The mean ± SD age for males was 19.2 years ± 3.22 years and for females was 19.4 years ± 1.14 years. Conclusion: The results indicate that there is no significant relationship between tests that assess core stability and tests conducted to assess dynamic balance in active young adults. With the exception of the abdominal flexion test, no significant relationship exists between the remaining core stability tests and agility T-Test. Core stability is not a determinant of balance and agility.

Endolysin of bacteriophage T5 (EndoT5) is a Zn2+-dependent and Ca2+-activated L-alanyl-D-glutamate peptidase that hydrolyses peptidoglycans during the destruction of the cell wall of the phage host bacterium Escherichia coli. To elucidate the mechanism of calcium activation, the spatial solution structure of EndoT5 in a complex with two ions - catalytic Zn2+ and regulatory Ca2+ (EndoT5-Zn2+Ca2+, PDB ID: 8P3A) was determined by high-resolution NMR and deposited in the Protein Data Bank. We show that coordination of the Ca2+ ion fix the spatial position of polar amino acid residues D113, N115 and S117. As a result, the intramolecular mobility of extended protein loops (residues 40-70 and 111-132) is significantly reduced compared to the mobility of these loops in the structure of an enzyme containing only a catalytic a Zn2+ ion (EndoT5-Zn2+, PDB ID: 2MXZ). In the stabilized EF-like calcium-binding loop (residues 111-132), the number of van der Waals interactions with amino acid residues of the globular core of the protein increases. The binding of the Ca2+ ion is accompanied by the selection of the functional states of both extended loops of the enzyme (residues 40-70 and 111-132), because of which EndoT5-Zn2+Ca2+ acquires the structural integrity necessary for catalysis. Therefore, the mechanism of activation of L-alanyl-D-glutamate peptidase of bacteriophage T5 by Ca2+ ions involves stabilization of the enzyme molecule in a catalytically active “open” conformation. This work sheds light on the structural grounds of the ion-dependent functional proteoforms of this interesting protein.

Abstract: Spinal disorders are some of the most prevalent health concerns, especially among stu-dents. Based on student demographics, this cross-sectional study evaluated the correlation be-tween functional tests (FT) and spinal range of motion (ROM). This study included 206 students from Vasile Alecsandri University of Bacău. Participants' assessments were conducted using the following tests: (i) Ott, (ii) Schober, (iii) Stibor, (iv) finger-to-floor distance, (v) lateral flexion of the cervical and lumbar spine, and (vi) flexion of the cervical spine. Correlation analyses were evaluated using Spearman correlation coefficient analysis. The results indicated a very strong re-lationship between lateral flexion of the lumbar spine on the left (LFLSL) and right (LFSR) for all departments (r = 0.85 to 0.97, p < 0.05). There was a stronger relationship between FT results and spinal ROM of physical education department students compared to students from other de-partments (n = 17, r = -0.38 to 0.93, p < 0.05). There was no statistically significant correlation be-tween FT and spinal ROM based on age (p > 0.05). The study results provide evidence of the pri-mary risk factors that predispose students to postural deviations. Practitioners and physiothera-pists can utilize these values as a reference for potential therapeutic interventions.

Hereditary cardiomyopathies (CMPs), including Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), Dilated Cardiomyopathy (DCM), and Hypertrophic Cardiomyopathy (HCM), represent a group of heart disorders that significantly contribute to cardiovascular morbidity and mortality and are often driven by genetic factors. Recent advances in Next-Generation Sequencing (NGS) technology have enabled the identification of rare variants in both well-established and minor genes associated to CMPs. Nowadays, a set of core genes is included in diagnostic panels for ARVC, DCM, HCM. On the other hand, despite their lesser-known status, variants in the minor genes may contribute to disease mechanisms and influence prognosis. This review evaluates the current evidence supporting the involvement of the minor genes in CMPs, considering their potential pathogenicity and clinical significance. A comprehensive analysis of databases such as ClinGen, ClinVar, and GeneReviews, along with recent literature and diagnostic guidelines, provides a thorough overview of the genetic landscape of minor genes in CMPs and offers insights for future research and translation to clinical practice. Given the increasing knowledge on these less-understood genetic factors, future studies are essential to clearly assess their roles, ultimately leading to improved diagnostic precision and therapeutic strategies in hereditary CMPs.

New antimicrobial approaches are essential to counter antimicrobial resistance. The drug development pipeline is exhausted with emergence of resistance resulting in unsuccessful trials. The lack of an effective drug developed from the conventional drug portfolio has mandated the introspection into the list of potentially effective unconventional alternate antimicrobial molecules. Alternate therapies, that are clinically explicable forms include monoclonal antibodies, antimicrobial peptides, aptamers and phages. Clinical diagnostics optimizes the drug delivery. In the era of diagnostic-based applications, it is logical to draw diagnostic based treatment for infectious diseases. Selection criteria of alternate therapeutics in infectious disease include detection, monitoring of response and resistance mechanism identification. Integrating these diagnostic applications is disruptive to the traditional therapeutic development. The challenges and mitigation methods need to be noted. Applying the goals of clinical pharmacokinetics that include enhancing efficacy and decreasing toxicity of drug therapy this review analyses the strong correlation of alternate antimicrobial therapeutics in infectious diseases. The relationship between drug concentration and the resulting effect defined by the pharmacodynamic parameters are also analyzed. This review analyzes the perspectives of aligning diagnostic initiatives into the use of alternate therapeutics with a particular focus on companion diagnostic applications in infectious diseases.

Research into lightweight structural concrete using volcanic tuff is of great importance to the construction industry. These materials have excellent thermal insulation properties, which helps improve the energy efficiency of buildings. A three-factor experimental design was used to build the statistical model. The test methods used were methods for determining the crushability of volcanic tuff, determining the average density, compressive strength and thermal conductivity of lightweight structural concrete. The influence of basalt fiber on the properties of lightweight structural concrete has been determined. The optimal compositions of lightweight structural concrete using tuff have been selected. The compressive strength of lightweight structural concrete reached 32.0 MPa. The average density range is 1754.6-2114.0 kg/m³. Good thermal conductivity values ​​were obtained in the range of 0.653-0.818 W/m·K. The article obtained the optimal compositions of lightweight structural concrete using volcanic tuff as a filler.

LONP1 is the principal AAA+ unfoldase and bulk protease in the mitochondrial matrix, so its deletion causes embryonic lethality. The AAA+ unfoldase CLPX and the peptidase CLPP also act in the matrix, conspicuously during stress periods, but their substrates are poorly defined. Mammalian CLPP deletion triggers infertility, deafness, growth retardation, and cGAS-STING activated cytosolic innate immunity. CLPX mutations impair heme biosynthesis and heavy metal homeostasis. CLPP and CLPX are conserved from bacteria to human, despite their secondary role for proteolysis. Based on recent proteomic-metabolomic evidence from knockout mice and patient cells, we propose that CLPP acts on phase-separated ribonucleoprotein granules, and CLPX on multi-enzyme condensates, near the inner mitochondrial membrane, as first-aid system. Trimming within assemblies, CLPP rescues stalled processes in mitoribosomes, in mitochondrial RNA granules and nucleoids, and in D-foci-mediated degradation of toxic double-stranded mtRNA / mtDNA. Unfolding multi-enzyme condensates, CLPX maximizes PLP-dependent delta-transamination, and rescues malformed nascent peptides. Overall, their actions occur in granules with multivalent or hydrophobic interactions, separated from the aqueous phase. Thus, the role of CLPXP in the matrix is compartment-selective, like peptidases MPP at precursor import pores, m-AAA and i-AAA at either IMM face, PARL within the IMM, and OMA1/HTRA2 in the intermembrane space.

Abscisic acid (ABA) is a conserved “stress hormone” in unicellular organisms, plants and animals. In mammals, ABA and its receptors LANCL1 and LANCL2 stimulate insulin-independent cell glucose uptake and oxidative metabolism: overexpression of LANCL1/2 increases, and their si-lencing conversely reduces, mitochondrial number, respiration and proton gradient dissipation in muscle cells and in brown adipocytes. We hypothesized that the ABA/LANCL hor-mone/receptors system could be involved in thermogenesis. Heat production by LANCL1/2-overexpressing vs. double-silenced cells was compared in rat H9c2 cardiomyocytes with two different methods: differential temperature measurements using sensitive thermistor probes, and differential isothermal calorimetry. Results indicate that overexpressing cells generate an approx. double amount of thermal power compared with double-silenced cells, and that addition of ABA further doubles heat production in overexpressing cells. With the temperature probes, we find a time-scale of approx. 4 min for thermogenesis to “turn on” after nutrient addition. These results identify the ABA/LANCL hormone receptors system as a hitherto unknown regu-lator of cell thermogenesis. Pharmacologic means of increasing metabolic energy dissipation are considered a promising strategy to reduce oxidative stress and lipid accumulation at a cellular and organismic level: from this study, LANCL1-2 proteins emerge as targetable controllers of ther-mogenesis through their natural ligand ABA.

Abstract: Lipodystrophies (LDs) are rare, complex disorders of the adipose tissue characterized by selective fat loss, altered adipokines profile and metabolic impairment. Sirtuins (SIRTs) are class III NAD+-dependent histone-deacetylases linked to fat metabolism. SIRT1 plays a critical role in metabolic health by deacetylating target proteins in tissues including liver, muscle and adipose tissue. Circulating SIRT1 levels have been found to be reduced in obesity while increased in anorexia nervosa and in patients experiencing weight loss. We evaluated circulating SIRT1 levels in relation to fat amount in 32 lipodystrophic patients affected by congenital or acquired LDs compared to non-LD subjects (24 with anorexia nervosa, 22 normal weight and 24 with obe-sity). SIRT1 serum levels were higher in LDs as compared with normal weight subjects (mean ± SEM: 4.17 ± 0.48 vs. 2.59 ± 0.20 ng/mL) or subjects with obesity (1.7 ± 0.39 ng/mL), whereas they were close to those measured in anorexia nervosa (3.44 ± 0.46 ng/mL). Our findings show that within the LD group there was no relationship between SIRT1 levels and the amount of body fat. The mechanisms responsible for secretion and regulation of SIRT1 in LD deserve further investi-gation.

In this paper, we introduce a specialized, fully automated experimental arrangement designed for assessing the effectiveness of augmented and virtual reality technologies in healthcare setting and explore its design principles focusing on depth sensor characterization. The main goal of this project is to establish a robust benchtop platform for the quantitative evaluation of extended reality technologies in a controlled environment, emphasizing the practical assessment of augmented reality head-mounted devices. We outline a design concept and considerations for an experimental configuration aimed at creating a realistic testing environment. This apparatus comprises an observation platform mounted on a three-degree-of-freedom motorized system and a test phantom stage. Focusing on real-case scenarios, we utilized a range of sensors, including readily available range-sensing cameras and commercial augmented reality headsets, such as the Intel RealSense L515 LiDAR camera, mounted on the motion control system. The setup enabled automated data collection and facilitates controlled assessments and validation of various facets of augmented reality technologies, including object, hand, and head tracking, as well as static and dynamic image registration. This paper describes the system architecture, the process of automated data collection, and presents several evaluation studies conducted with this setup, providing insights into the quality and temporal noise associated with static or moving objects or observers in augmented reality applications.

Menin inhibitors are new and promising agents currently in clinical development that target the HOXA/MEIS1 transcriptional program which is critical for leukemogenesis in histone-lysine N-methyltransferase 2A rearranged (KMT2Ar) and in NPM1-mutated (NPM1mut) acute leukemia. The mechanism of action of this new class of agents is based on the disruption of menin-KMT2A complex (constitute of chromatin remodelling proteins), leading to the differentiation and apoptosis of AML cells expressing KMT2A or mutated NPM1. This new class of drugs has been tested alone, or in combination with synergistic drugs, in phase I and II clinical trials (AUGMENT-01 and 02, KOMET-01 and 07, SAVE, COVALENT trial and others), showing promising results in terms of response rates and safety in heavily pre-treated acute leukemia patients. In this review, we summarise the key findings on menin inhibitors, focusing on the mechanism of action and preliminary clinical data of this emerging and promising class of agents, in particular revumenib and ziftomenib.

Background: Vestibular Neuritis (VN) induces Acute Vestibular Syndrome (AVS). This study aimed to identify predictive factors of VN recovery by healing and/or compensation. Methods: In this longitudinal and prospective study, 40 patients were included. The first assessment (T0) included medical history taking (general and specific), for cardiovascular risk factors (CVRFs), a battery of diagnostic tests, bithermal caloric test (BCT), video Head Impulse Test (VHIT) and skull vibration induced nystagmus (SVIN). All patients also completed a Dizziness Handicap Inventory (DHI). All assessments were repeated 90±15 days (T3) later. Subjective criteria compensation were based on DHI total score and objective criteria compensation on the instrumental test results. Four groups of patients (A, B, C, D) were delineated by combining patients with normal vs abnormal vestibular tests and patients with normal vs abnormal DH. Results: CVRFs were associated with a poorer recovery of symptoms but not the age or BMI. Vestibular tests mainly BCT (canal paresis %), VHIT (lateral semicircular canal gain) and SVINT (nystagmus slow phase velocity) recovered within normal values in 20%, 20%, 26% of cases respectively at T3 for the 40-patient group. Conclusions: Vascular risk factors (hypercholesterolemia) are correlated with patients who do not recover their symptoms either by healing or compensation. The evolution did not show any significant difference between high or low frequency vestibular tests in patients recovering from their symptoms. However, some patients with objective recovery may continue to show persisting subjective symptoms.

Background: Liver failure profoundly affects the immune system, leading to dysregulation of innate and adaptive immune responses. Body: This review explores the intricate relationship between liver function and immune homeostasis. The role of the liver as a central hub in immune response initiation is elucidated, emphasizing its involvement in hepatic inflammation induction and subsequent systemic inflammation. Cytokines, chemokines, growth factors, and lipid mediators orchestrate these immune processes, serving as both prognostic biomarkers and potential therapeutic targets in liver failure-associated immune dysregulation. Furthermore, the review delves into the mechanisms underlying immunosuppression in liver failure, encompassing alterations in innate immune cell functions such as neutrophils, macrophages, and natural killer cells (NK cells), as well as perturbations in adaptive immune responses mediated by B and T cells. Conclusion: Understanding the immunological consequences of liver failure is crucial for developing targeted therapeutic interventions and improving patient outcomes in liver disease management.

The field of construction materials is pivotal in developing sustainable and resilient infrastructure. This demands continuous research to understand the properties and behaviors of these materials under diverse conditions. Although advancements in material science and numerical modeling have been significant, experimental testing remains indispensable for a thorough comprehension of material characteristics, particularly under extreme stresses and environmental factors. This need has forced the development of a wide array of testing techniques, each designed to evaluate specific engineering properties, thus creating a complex and varied landscape of experimental methodologies. This study provides a comprehensive overview of both conventional and innovative experimental testing techniques used to characterize construction materials. It explores the related methodologies and identifies potential gaps in their application within the industry. The spectrum of testing covered includes mechanical, chemical, thermal, microstructural, durability, physical, rheological properties, and non-destructive testing methods. Mechanical tests assess strength, hardness, and fatigue, whereas chemical analyses utilize techniques such as spectroscopy and chromatography. Thermal properties are examined using thermogravimetric analysis, and microstructural characteristics are explored through advanced imaging techniques. Durability testing focuses on materials’ resistance to environmental challenges, while physical properties tests evaluate aspects like porosity and water absorption. Rheological and non-destructive tests further examine materials’ behavior and integrity without causing damage. By discussing these methodologies, the study sheds light on various approaches to material evaluation and aims to enhance the selection, application, and development of testing standards. This overview seeks to inform and inspire future research and innovation in the science of construction materials, contributing to the development of more resilient and sustainable construction practices.

Within the spectra of lanthanide atoms quite often overlapping spectral lines (blends) are observed. On the example of complicated blend situations within Pr I and La I it is shown that in such cases a combination of optogalvanic and laser-induced fluorescence detection is necessary to find all transitions contributing to the observed spectral signature.

Abstract: Giant Cell Arteritis (GCA) is an autoimmune/autoinflammatory disease affecting large vessels in patients over 50 years old. The disease presents as an acute inflammatory response with two phenotypes, cranial-GCA and Large Vessel Vasculitis (LV)-GCA, involving the thoracic aor-ta and its branches. 18F-fluorodeoxyglucose positron emission tomography-computed tomogra-phy (18F-FDG PET-CT) is among the imaging techniques contributing to diagnosis of patients with systemic disease. However, its association with soluble inflammatory markers is still elu-sive. This proof-of-concept study aims to identify novel soluble serum biomarkers in PET/CT pos-itive patients with LV-GCA and associate them with active (0 months) and inactive disease (6 months following treatment), in sequential samples. The Most-Disease-Segment Target-to-Background Ratio (TBRMDS) was calculated for 9 LV-GCA patients, while 12 cranial-GCA and 7 Polymyalgia Rheumatica patients with negative initial PET/CT served as disease controls. Serum macrophage-related cytokines were evaluated by Cytometric Bead Array (CBA). Finally, previously published NMR-metabolomics data acquired at the same blood sampling were associated with PET/CT findings. TBRMDS was significantly increased in active versus inactive disease (3.45 vs. 2.55, p=0.008). The analysis identified 6 serum metabolites, as more sensitive to change from the active to inactive state. Among them, choline levels were exclusively altered in the LV-GCA group, but not the disease controls. Cytokine levels were not associated with PET/CT activity. Combining with CRP, ESR, and TBRMDS a composite index was generated to depict well the differences between active and inactive systemic LV-GCA (25.45 vs 11.45, p=0.0039). These preliminary results could pave the way for more extensive studies integrating serum metabolomic parameters with PET/CT imaging data to extract sensitive composite disease indexes useful for the everyday clinical practice.

Extruded polystyrene (XPS) is frequently used in the construction of many different structures. It is therefore necessary to appropriately characterize its mechanical properties to ensure the safety of said structures. Among the available characterization tests, static bending tests are simple and easy to perform; owing to these characteristics, they should be performed more frequently than other tests. However, in static bending tests on XPS, there are several challenges owing to the high flexibility of XPS, and the chosen testing method and sample configuration affect the accuracy of characterization. In this study, three bending properties (Young’s modulus, proportional limit stress, and bending strength) of samples cut from an XPS panel were determined using three-point bending (TPB), four-point bending (FPB), and compression bending (CB) tests with varying sample span/depth ratios, and statistical analyses were performed to determine the relevance of the tests. The experimental results suggest that the TPB and CB tests were more feasible than the FPB test when the span/depth ratio was appropriately determined. However, clear differences were observed in the sample bending properties determined in these tests. In light of these findings, further studies should be conducted to elucidate these differences.

Performing optimisation and scale-up studies of crystallisation systems requires accurate and computationally efficient mathematical models. The assumption of the ideal mixing conditions in batch reactors typically produce inaccurate results while the computational expense of CFD models is still prohibitively high. Therefore, in this work, a new intermediary approach is proposed that takes into account the non-ideal mixing conditions in the reactor and requires less computational resources than full CFD simulations. Starting with the Danckwerts concept of the intensity of segregation, an analogy between its application to chemical reactions and the kinetics of the crystallisation phenomena (such as nucleation and growth) has been made. As a result, the modified kinetics expressions have been derived which incorporate the effect of non-idealities present in stirred reactors. This way, based on the experimental measurements of the mixing time using the Laser Induced Fluorescence (LIF) technique, computationally more efficient mathematical models can be developed in two ways: (1) the accurate semi-empirical correlations are available for standard mixing configurations with the most often used types of impellers, (2) CFD simulations can be utilised for estimation of the mixing time; in this case it is necessary to simulate only the mixing process. The benefits offered by the LIF experimental technique have been demonstrated and some frequent problems in its application analysed. The mixing time results for configurations with and without baffles for three types of impellers and four different rotational speeds have been presented. The false shorter mixing times in the non-baffled configurations have been observed and this phenomena explained by the existence of two segregated zones in the reactor and confirmed by additional experiments. The precise measurements in these cases have been shown as difficult using the LIF technique, particularly for higher rpms. The experimental data has been compared to the preliminary simulation results obtained from the Smoothed Particle Hydrodynamics method and the standard k-ε turbulence model with the modest success. The shortcomings of the SPH model have been recognized and the directions for the future work discussed.

This study investigates the performance and environmental impact of n-butanol blended with Jet-A fuel in turbo-engines, aiming to assess its viability as a sustainable aviation fuel (SAF). The research involves experimental testing of various blends, ranging from low to high concentrations of methanol, to determine their effects on engine performance and emissions. The experimental setup includes comprehensive measurements of engine parameters such as thrust, fuel consumption rates, and exhaust gas temperatures. Emissions of nitrogen oxides (NOx), particulate matter (PM), carbon monoxide (CO), and unburned hydrocarbons (HC) are also analysed to evaluate environmental impacts. Key findings indicate that n-butanol/Jet-A blends can significantly enhance combustion efficiency and reduce emissions compared to conventional Jet-A fuel. Higher n-butanol concentrations lead to improved thermal efficiency and lower NOx and CO emissions. However, PM emissions slightly increase with higher methanol content. The study underscores the potential of n-butanol as a SAF for turbo-engines, highlighting its ability to mitigate environmental impacts while maintaining or improving engine performance. This research supports the feasibility of integrating n-butanol into Jet-A blends for turbo-engine applications, emphasizing its role in achieving more environmentally friendly aviation operations.

In Mexico there is a deficit in the production of pine resin, because it depends on natural forests. Therefore, it is necessary to select provenances and phenotypes of potential species such as P. oocarpa. The objective was to determine the difference between provenances and the variation of resin components and quality, as well as the effect of geographic and climatic factors. Resin from five provenances was collected from southern Mexico. The percentage of rosin, turpentine and water was obtained, as well as the acidity and saponification index. P. oocarpa resin had 80.94 % rosin, 7.7 % turpentine and 11.49 % water. The saponification and acidity index was 125.47 and 117.49 mg KOH.g_1, respectively. All variables showed differences (p≤ 0.0001) between provenances. The provenance contributed between 6.44 and 11.71 % to the total variance, the error contributed between 88.29 and 93.56 %. Geographic and climatic variables only had an effect on the percentage of turpentine; the correlation was negative with altitude and longitude, but positive with temperature and precipitation. The results allow defining seed collection sites for resin plantations and orienting the selection for a P. oocarpa improvement program.

The main purpose of this study is the determination of the optimal data acquisition and processing parameters of electric and seismic tomographic techniques, for the investigation of complex geological environments. Two different study areas, in central-east Peloponnese and SW Attica were selected, where a detailed geological mapping and surface geophysical survey were carried out. The applied geophysical survey included the application of electrical resistivity tomography (ERT) and seismic refraction tomography (SRT). The geoelectrical measurements were acquired with different arrays and electrode configurations. Moreover, various types of seismic sources were used at seventeen shot locations along the seismic arrays. For the processing of geoelectrical data, clustered datasets were created increasing the depth of investigation and the discriminatory capability. The seismic data processing included: (a) creation of synthetic models and seismic records to determine the effectiveness and capabilities of the technique, (b) spectral analysis of the seismic records to determine the optimal seismic source type and (c) inversion of the field data to create representative subsurface velocity models. The results of the two techniques successfully delineated the complex subsurface structure that characterizes these two geological environments. The application of the ERT combined with the SRT, are the two dominant, high-resolution techniques for the elucidation of complex subsurface structures.

Phased injection of natural gas into internal combustion marine engines is a promising solution for optimizing performance and reducing harmful emissions, particularly unburned methane, a potent greenhouse gas. This innovative practice distinguishes itself from continuous injection because it allows for more precise control of the combustion process with only a slight increase in system complexity. By synchronizing the injection of natural gas with the intake and exhaust valve opening and closing times while also considering the gas path in the manifolds, methane release into the atmosphere is significantly reduced, making a substantial contribution to efforts to address climate change. Moreover, phased injection improves the efficiency of marine engines, resulting in reduced overall fuel consumption, lower fuel costs, and increased ship autonomy. This technology has been tested on a single-cylinder, large-bore, four-stroke research engine designed for marine applications, operating in dual-fuel mode with diesel and natural gas. Performance was compared with that of the conventional continuous feeding method. Evaluation of the effect on equivalent CO2 emissions indicates a potential reduction of up to approximately 20%. This reduction effectively brings greenhouse gas emissions below those of the diesel baseline case, especially when injection control is combined with supercharging control to optimize the air-fuel ratio.

The study aimed to evaluate the nutritional value of watermelon plant silage (WPS) and to assess the effect of replacing alfalfa hay (AH) with WPS in a diet formulated for dairy goats. The study used four goats as donors of rumen microbiota to analyze in vitro fermentation parameters. The chemical composition analysis revealed that WPS and AH had similar protein content (21.1 vs. 18.9 g CP/100 g DM), but WPS had lower contents of organic matter (77.4 vs. 89.6 g/100 g DM), NDF (36.3 vs. 49.4 g/100 g DM), ADF (26.4 vs. 34.6 g/100 g DM), LAD (6.40 vs. 8.01 g/100 g DM), and amino acids (716 vs. 874 g AA/kg N) compared to AH. Conversely, WPS had higher fat content (3.09 vs. 1.29 g CF/100 g DM) and different macro- and micromineral content values than AH. In a first in vitro experiment, WPS and AH were incubated independently to compare their fermentation behaviour, indicating that the metabolizable energy (ME) tended to be higher for WPS compared to the AH diet (6.67 vs. 5.72 MJ/kg DM; p = 0.058). WPS fermentation produced lower concentrations of total VFA than AH (66.6 vs. 115 mM; p = 0.011), lower proportions of propionate and valerate (p ≤ 0.022), and higher proportions of isobutyrate (p = 0.001), without altering gas production (GP) kinetics as degradation rate and its potential release. In a second in vitro trial, a formulated goat diet (consisting of commercial concentrate and AH in a 1:1 ratio) was used as a control to assay the impact of AH replacing by WPS at 25% and 50% respectively. Trends were observed in several parameters, such as a linear increase in GP rate (p = 0.088), organic matter digestibility (p = 0.067), and CH4 concentration in the gas produced (p = 0.094) as AH was replaced by WPS. The study concluded that WPS could serve as a viable fodder to replace AH in conventional dairy goat diets while simultaneously reducing agricultural waste and serving as a regenerative model for implementing the circular economy strategy in the affected sectors.

Background. Amyotrophic Lateral Sclerosis (ALS) is a devastating disease involving motor neuron degeneration. The few drugs approved for treatment have at most a marginal benefit, and death usually occurs 2-5 years after diagnosis. Methods. A thorough manual examination of the relevant literature, covering over 35,000 papers. Results. Two major phenomena that are generally not known to clinicians were found. First, insulin signaling is impaired in ALS even in patients not diagnosed with diabetes (DB). Almost all studies that have explicitly tested insulin function in non-DB ALS patients using glucose tolerance tests (18 out of 20, 1964-2022, different groups) have found it to be impaired. Second, there is strong evidence for excessive insulin-independent glucose uptake (IIGU) in ALS. In addition, (i) early/late diabetes are associated with increased/decreased risk, respectively; (ii) insulin-based diabetes drugs are protective in ALS in large retrospective human studies; and (iii) strong animal and human evidence shows that insulin opposes all of the major pathological processes in ALS. Conclusion. Most ALS patients have insulin impairment, yet this is commonly not diagnosed, likely because excessive IIGU normalizes glucose levels. The impairment promotes disease progression. Late diabetes is associated with decreased risk because high glucose levels indicate non-excessive IIGU, and because diabetes drugs are protective. Insulin-based treatment (e.g., GLP1 agonists, insulin) is beneficial and can be disease-modifying in ALS and in frontotemporal dementia variants comorbid with ALS. ALS patients should be routinely tested for insulin function and treated if test results are positive.

The main foundations of the standard $\Lambda $CDM model of cosmology are that: 1) The redshifts of the galaxies are due to the expansion of the Universe plus peculiar motions; 2) The cosmic microwave background radiation and its anisotropies derive from the high energy primordial Universe when matter and radiation became decoupled; 3) The abundance pattern of the light elements is explained in terms of primordial nucleosynthesis; and 4) The formation and evolution of galaxies can be explained only in terms of gravitation within a inflation+dark matter+dark energy scenario. Numerous tests have been carried out on these ideas and, although the standard model works pretty well in fitting many observations, there are also many data that present apparent caveats to be understood with it. In this paper, I offer a review of these tests and problems, as well as some examples of alternative models.

Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-aminofluorene (2-AAF). HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, β-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation.

Augmented and Virtual Reality have been experiencing a rapidly growth in recent years, but there is not still a deep knowledge on their capabilities and where they could be explored. In that sense, this paper presents a study on the accuracy and repeatability of the Microsoft's HoloLens 2 (Augmented Reality device) and HTC Vive (Virtual Reality device) using an OptiTrack system as ground truth. For the HoloLens 2, the method used was hand tracking, while in HTC Vive, the object tracked was the system's hand controller. A series of tests in different scenarios and situations were performed to explore what could influence the measures. The HTC Vive obtained results in the millimetre scale, while the HoloLens 2 revealed not so accurate measures (around 2 centimetres). Although the difference can seem to be considerable, the fact that HoloLens 2 was tracking the user's hand and not an inherit controller made a huge impact. The results were considered a significant step for the on going project of developing a human-robot interface to program by demonstration an industrial robot using Extended Reality, which shows great potential to succeed based on this data.

An extensive review of literature simulations of polymer melts is given, considering results that test aspects of the Rouse model in the melt. We focus on the mean-square amplitudes < (X_p(0))^{2} > and time correlation functions < X_p(0) X_p(t) > of the Rouse modes $X_p(t)$. Contrary to the Rouse model: (i) Mean-square Rouse mode amplitudes < (X_p(0))^2> do not scale as sin^{-2}(p \pi/2N), N being the number of beads in the polymer. For small p (say, p <= 3) < (X_p(0))^2> scales with p as p^{-2}$; for larger p it scales as p^{-3}. (ii) Rouse mode time correlation functions < X_p(t) X_p(0) > do not decay with time as exponentials; they instead decay as stretched exponentials exp(-a t^b)$. b depends on p, typically with a minimum near N/2 or N/4. (iii) Polymer bead displacements are not described by independent Gaussian random processes. (iv) For p not equal to q, < X_p(t) X_{q}(0) > is sometimes non-zero. (v) The response of a polymer coil to a shear flow is a rotation, not the affine deformation predicted by Rouse. Simulations thus conclusively demonstrate that the Rouse model is invalid in polymer melts. We also briefly consider the Kirkwood-Riseman polymer model.

The aim of this paper is to establish a valid procedure for better understanding all the phenomena associated with the high-speed machining of Glass Fibre Reinforced Plastic (GFRP) composites. Both rectangular and circular specimens were machined at high speeds (up to 50 m/min) in order to understand what occurred for all values of fiber orientation angles during machining operations. An innovative testing methodology was proposed and studied to investigate the phenomenon of burr formation and thus understand how to avoid it during machining operations. To this end, the forces arising during the machining process and the roughness of the resulting surface, were carefully studied and correlated with the cutting angle. Additionally, the cutting surface and chip morphology formed during cutting tests were examined using a high-speed camera. Close correlations are found between the variations of the cutting forces' signals and the trends of the roughness and the morphology of the machined surface.

Background: Colorectal adenoma undergoes neoplastic progression via the normal epithelium-adenoma-adenocarcinoma sequence as reported in the Vogelgram. The risk of developing cancer is strongly associated with the number and size of adenoma and with the subtype. Currently, adenomatous polyps can be distinguished on the basis of histology: the prevalence are tubular, 5-15% are villous and tubular/villous. Considering the increased risk for malignant transformation described for tubular/villous adenomas, patients diagnosed with adenomatous polyposis are at increased risk of developing CRC. The Wnt/β-catenin pathway plays a key role in the onset of colorectal adenoma, in particular intestinal cells first acquire loss-of-function mutations in APC gene that induce the formation of adenomas. Methods: Wnt/β-catenin pathway APC, Wnt3a, Wnt5a, LEF1, BCL9 genes and protein expression analyses were conducted by qRT-PCR and western blot in 68 colonic samples (polyps and adjacent mucosa) from 41 patients, of which 17 affected by FAP. Ten normal colonic mucosal samples were collected from 10 healthy donors. Results: In this study both APC gene and protein resulted less expressed in colon tumor compared to the adjacent colonic mucosa. Conversely, activated β-catenin was more expressed in polyps than in the adjacent mucosa. All results confirmed literature data on carcinomas. A statistically significant correlation between Wnt3a and BCL9 both in polyps and in the adjacent mucosa underlies that the canonical Wnt pathway is activated in early colon carcinogenesis and that the adjacent mucosa is already altered. Conclusion: This is the first study analyzing the difference in expression of Wnt/β-catenin pathway in human colorectal adenomas. Understanding the progression from adenomas to colorectal carcinomas is essential for the development of new therapeutic strategies and improving clinical outcomes.

The electric vehicle (EV) industry challenges battery joining technologies by requiring higher energy density both by mass and volume. Improving the energy density via new battery chemistry would be the holy grail but is seriously hindered and progresses slowly. In the meantime, alternative ways, such as implementing more efficient cell packaging by minimizing the electrical resistance of joints are of primary focus. In this paper we discuss the challenges associated with the electrical characterisation of laser soldered joints in general, and the minimization of their resistive losses, in particular. In order to assess the impact of the joint resistance on the overall resistance of the sample, the alteration in resistance was monitored as a function of voltage probe distance and modelled by finite element simulation. The experimental measurements showed two different regimes: one far from of the joint area and another in its vicinity and within the joints cross section. The presented results confirm the importance of the thickness of the filler material, the effective and the total soldered area, and the area and the position of the voids within the total soldered area in determining the electrical resistance of joints.

Acquired immunodeficiency syndrome (AIDS) has transitioned from a progressive, fatal disease to a chronic, manageable disease thanks to better defining of antiretroviral therapy, hence contributing to increased life expectancy. In parallel, a growing number of subjects without overt clinical signs of disease but living with chronic HIV infection (people living with HIV, PLWH) are experiencing early cardiovascular disease worldwide. However, a progressive increase in the prevalence of multiple comorbid diseases has been reported as these patients age, including cardiovascular disease (CVD). Cardiovascular mortality can be either directly related to the viral infection, a progressive reduction of response to the antiretroviral therapy, chronic inflammation or lifestyle-related. Cardiovascular ageing represents a relevant issue in the management of HIV-infected patients. Although the exact pathophysiological mechanism that leads PLWH to develop cardiovascular disease is not entirely understood, there is substantial evidence that they accumulate age-related conditions earlier than the general population. Furthermore, since the proportion of PLWH growing older than 50 years has progressively increased, this results in a complex interaction between disease-related pathophysiology and the exposition of a growing burden of cardiovascular risk factors. For this reason, we performed a systematic review of the genes most frequently associated with ageing in HIV-infected subjects, followed by a bioinformatic analysis to explore the biological impact of the genes related to ageing.

The olive tree (Olea europaea L.) is an evergreen tree that occupies 19% of the woody crop area and is cultivated in 67 countries on five continents. The largest olive production is concentrated in the Mediterranean basin, where the olive tree has had an enormous economic, cultural and environmental impact since the 7th century BC. In the Mediterranean region, salinity stands out as one of the main abiotic stress factors significantly affecting agricultural production. Moreover, climate change is expected to lead to increased salinisation in this region, threatening olive productivity. Salt stress causes combined damage by osmotic stress and ionic toxicity, restricting olive growth and interfering with multiple metabolic processes. A large variability in salinity tolerance among olive cultivars has been described. This paper aims to synthesize information from the published literature on olive adaptations to salt stress and its importance in salinity tolerance. The morphological, physiological, biochemical, and molecular mechanisms of olive tolerance to salt stress are reviewed.

There is a need to find methods to intensify the anaerobic digestion process. One possibility is the use of pre-treatment techniques. Many laboratory tests confirm their effectiveness, but in most cases, there is no verification work carried out on industrial plants. The aim of the research carried out under laboratory conditions and on a large scale was to determine the technological and energy efficiency of the use of hydrodynamic cavitation in the pre-treatment of a waste mixture from dairy farms. It has been shown that hydrodynamic cavitation significantly increases the concentration of organic compounds in the dissolved phase. In the most effective variants, the increase in the content of these indicators was over 90% for both COD and TOC. The degree of solubilisation achieved was 49±2.6% for COD and almost 52±4.4% for TOC. Under laboratory conditions, the highest effects of anaerobic digestion were achieved after 10 minutes of pre-treatment. The amount of biogas was on average 367±18 mL/gCOD and the amount of methane 233±13 mL/gCOD. Further large-scale optimisation trials showed that after 8 minutes of hydrodynamic cavitation, the biogas yield was 327±8 L/kgCOD with a CH4 content of 62.9±1.9%. With this variant, the net energy yield was 66.4±2.6 kWh/day, a value that was 13.9% higher than the original variant with 10 minutes of disintegration and 3.1% higher than the variant without pre-treatment.

Purpose. This paper aims to present a unique perspective that emphasizes the intricate interplay between energy, dietary proteins, and amino acid composition, underscoring their mutual dependence for health-related considerations. Energy and protein synthesis are fundamental to biological processes, crucial for the sustenance of life and growth of organisms. Methods and Results. We explore the intricate relationship between energy metabolism, protein synthesis, regulatory mechanisms, protein sources, amino acid availability, and autophagy, in order to elucidate how these elements collectively maintain cellular homeostasis. We underscore the vital role this dynamic interplay has in preserving cell life. Conclusion. A deeper understanding of the link between energy and protein synthesis is essential to comprehend fundamental cellular processes. This insight could have wide-ranging impact in several medical fields, such as nutrition, metabolism, and disease management.

Alzheimer's disease (AD) detection acting as an essential role in global health care due to misdiagnosis and sharing many clinical sets with other types of dementia, and costly monitoring the progression of the disease over time by magnetic reasoning imaging (MRI) with consideration of human error in manual reading. This paper goal a comparative study on the performance of data mining techniques on two datasets of Clinical and Neuroimaging Tests with AD. Our proposed model in the first stage, Apply clinical medical dataset to a composite hybrid feature selection (CHFS), for extract new features to select the best features due to eliminating obscures features, In parallel with Apply a novel hybrid feature extraction of three batch edge detection algorithm and texture from MRI images dataset and optimized with fuzzy 64-bin histogram. In the second stage, we applied a clinical dataset to a stacked hybrid classification(SHC) model to combine Jrip and random forest classifiers with six model evaluations as meta-classifier individually to improve the prediction of clinical diagnosis. At the same stage of improving the classification accuracy of neuroimaging (MRI) dataset images by applying a convolution neural network (CNN) in comparison with traditional classifiers, running on extracted features from images. The authors have collected the clinical dataset of 426 subjects with (1229 potential patient sample) from oasis.org and (MRI) dataset from a benchmark kaggle.com with a total of around ~5000 images each segregated into the severity of Alzheimer's. The datasets evaluated using an explorer set of weka data mining software for the analysis purpose. The experimental show that the proposed model of ‏(CHFS) feature extraction ‏ lead to effectively reduced the false-negative rate with a relatively high overall accuracy with a stack hybrid classification of support vector machine (SVM) as meta-classifier of 96.50% compared to 68.83% of the previous result on a clinical dataset, Besides a compared model of CNN classification on MRI images dataset of 80.21%. The results showed the superiority of our CHFS model in predicting Alzheimer's disease more accurately with the clinical medical dataset in early-stage compared with the neuroimaging (MRI) dataset. The results of the proposed model were able to predict with accurately classify Alzheimer's clinical samples at a low cost in comparison with the MRI-CNN images model at the early stage and get a good indicator for high classification rate for MRI images when applying our proposed model of SHC.

Using density functional theory (DFT), the density of states of NH4V3O8 (NVO) was analyzed pre and post-oxygen defects (Od) formation. The findings revealed a reduced bandgap in NVO after Od introduction, emphasizing the role of Od in enhancing conductivity of the material, thus improving its electrochemical attributes. Through the water bath method, both NVO and its oxygen-deficient counterpart, (NH4)2V10O25⸱8H2O (NVOd), were synthesized as potential cathode materials for aqueous zinc-ion batteries (AZIBs). Experimental outcomes resonated with DFT predictions, highlighting the beneficial role of oxygen defects in boosting electrical conductivity. Notably, the refined material displayed a remarkable capacity of 479.3 mAh g-1 at 0.1 A g-1, underscoring its promise for advanced energy storage solutions.

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation is analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors -of both primitive endocardial tubes- committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant nov-elty, our results revealed that miR-1 increases Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression, during early differentiation of cardiac sinoatrial region. Further-more, we observed in this developmental context that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacts with HDAC4 and Calmodulin, as well as with Erk2/MAPK1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in early differenti-ation of cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

Background: Autism spectrum disorder (ASD) is a persistent neurodevelopment disorder frequently co-occurring with Attention-Deficit/Hyperactivity Disorder (ADHD) and behavior-related disorders. While behavioral therapy is the first-line option to manage ASD core symptoms, pharmacological therapy is sometimes needed to treat acute problems, such as agitation and aggressive behaviors. Recent guidelines recommend neuroleptics to reduce psychomotor agitation in people with ASD. However, since children with ASD are often drug-resistant, alternative treatments are often justified. Reports from literature showed that intra-venous valproate (IV-VPA) can be effective in reducing agitation in psychiatric patients, with lower frequency of adverse events compared to convention-al treatments. However, since findings are occasionally inconsistent, IV-VPA is not an approved option in clinical psychiatry. We aim at improving the knowledge on the IV-VPA treatment option in emergency psychiatry in the pediatric age. Methods: We report the case of a 11-year-old boy suffering from a complex neurodevelopmental condition, who experienced a psychotic episode with severe aggressive and disruptive behaviors, successfully treated with IV-VPA. Besides, we conducted an up-dated literature review on this topic. Conclusion: In our case, first-line therapies proved to be ineffective. On the contrary, IV-VPA led to a safe and prompt clinical success, in line with other reports. Based on our literature review, IV-VPA can be highly effective and can reduce the risk of adverse events that frequently occur with the use of high-dose standard medications in emergency psychiatry.

A power factor correction (PFC) rectifier is compulsory for any electronic circuitry connected to the electrical grid. The majority of PFCs that are utilized are based on a step-up converter that supplies high DC voltage at its output terminal. Electric vehicle battery voltage varies from a few hundred to almost a thousand volts. Thus, an additional conversion step is obligatory when designing an all-brand universal charger. This paper presents a new type of front-end versatile step up / down three voltage level PFC. The rectifier can operate in continuous conduction mode or discontinuous conduction mode. First, the rectifier’s principle of operation is described, and then an innovative rectifier is analyzed for continuous and discontinuous conduction modes. Finally, the proposed theory is experimentally validated in a multiplier-less dual loop mode at discontinuous conduction modes. It was shown that although there is no multiplier use in the control circuitry, the power factor is near unity. It was revealed that the rectifier could swing the output voltage from 50 V to 900 V while the input voltage was 230 Vrms. The innovative topology suits any standard PFC rectifier, three-level voltage supplement, and dual-stage low-voltage power supply.

There is an important complementarity between experimental methods for the study of high-temperature viscoelasticity in the time and frequency domains, that has not always been fully exploited. Here we show that parallel processing of forced-oscillation data and microcreep records, involving consistent use of either Andrade or extended Burgers creep-function models, yields a robust composite modulus-dissipation dataset spanning a broader range of periods than either technique alone. In fitting this dataset, the alternative Andrade and extended Burgers models differ in their partitioning of strain between the anelastic and viscous contributions. The extended Burgers model is preferred because it involves a finite range of anelastic relaxation times, and accordingly a well-defined anelastic relaxation strength. The new strategy offers the prospect of better constraining the transition between transient and steady-state creep, or equivalently, between anelastic and viscous behaviour.

The paper presents construction, laboratory tests as well as the first field application of a new fiber-optic rotational seismograph. The system based on fiber-optic gyroscope (FOG) with determined Angle Random Walk of the order of 10-8 rad/Sqrt(s) and a few rad/s maximum detectable amplitude of rotation in the frequency range from DC to 328.12 Hz. It has been designed for rotational seismology area of interest. This work also presents exemplary relevant measurements which were conducted using a set of two devices installed in the geophysical observatory in Książ, Poland.

Abstract: MicroRNAs can interfere with a protein function by suppressing their messenger RNA translation or the synthesis of its related factors. The function of brain-derived neurotrophic factor (BDNF) is essential to the proper formation and function of the nervous system and is seen to be regulated by many microRNAs. However, understanding how microRNAs influence BDNF actions within cells requires a wider comprehension of their integrative regulatory mechanisms. Aim: In this literature review, we have synthesized the evidence of microRNA regulation on BDNF in cells and tissues, and provided an analytical discussion about direct and indirect mechanisms that appeared involved in BDNF regulation by microRNAs. Methods: Searches were conducted on PubMed.gov using the terms “BDNF” AND “MicroRNA” and “brain-derived neurotrophic factor” AND “MicroRNA”, updated on September 1st, 2023. Papers without open access were requested from the authors. One hundred and seventy-one papers were included for review and discussion. Results and Discussion: The local regulation of BDNF by microRNAs involves a complex interaction between a series of microRNAs with target proteins that can either inhibit or enhance BDNF expression, at the core of cell metabolism. Therefore, understanding this homeostatic balance provides resources for the future development of vector-delivery-based therapies for the neuroprotective effects of BDNF.

Ant rescue behaviour belongs to the most interesting subcategories of prosocial and altruistic behaviour encountered in the animal world. Several studies suggested that ants are able to identify what exactly restrains the movements of another individual and to direct their rescue behaviour precisely to that object. To shed more light on the question how precise is the identifi-cation of the source of restraint of another ant, we investigated rescue behaviour of workers of the red wood ant Formica polyctena using a new version of an artificial snare bioassay in which a nestmate victim was bearing on its body two wire loops, one placed on the petiole and acting as a snare, and an additional one on the leg. The tested ants did not direct preferentially their rescue behaviour to the snare. Moreover, the overall strategy adopted by the most active rescuers was not limited to precisely targeted rescue attempts directed to the snare, but consisted of attempts to find a solution to the victim’s problem through frequent trial-and-error switching between various subcategories of rescue behaviour. These findings highlight the importance of precise identifica-tion of cognitive processes and overall behavioural strategies for better understanding of causal factors underlying animal helping behaviour.

The keratinocyte carcinomas, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), are the most common cancers in humans. Recently, an increasing body of literature has investigated the role of miRNAs in keratinocyte carcinoma pathogenesis, progression and their use as therapeutic agents and targets, or biomarkers. However, there is very little consistency in the literature regarding the identity of and/or role of individual miRNAs in cSCC (and to a lesser extent BCC) biology. miRNA analyses that combine clinical evidence with experimental elucidation of targets and functional impact provide far more compelling evidence than studies purely based on clinical findings or bioinformatic analyses. In this study, we review the clinical evidence associated with miRNA dysregulation in KCs assessing the quality of validation evidence provided, identify gaps, and provide recommendations for future studies based on relevant studies that investigated miRNA levels in human cSCC and BCC. Furthermore, we demonstrate how miRNAs contribute to the regulation of a diverse network of cellular functions, and that large-scale changes in tumor cell biology can be attributed to miRNA dysregulation. We highlight the need for further studies investigating the role of miRNAs as communicators between different cell types in the tumor microenvironment. Finally, we explore the clinical benefits of miRNAs as biomarkers of keratinocyte carcinoma prognosis and treatment.

Rebar cages form the skeletal framework of reinforced concrete structural members. They comprise longitudinal and transverse reinforcing bars, usually connected by tie wires. Past studies have identified tie-wire connections as the "weak links" in large, prefabricated rebar cages, leading to their failure during site handling and construction stages. Recent research has explored the use of mechanical U-bolt connectors to bolster stability and safety of rebar cages while reducing their vulnerability and risk of failure. This paper presents a comprehensive experimental and numerical investigation of a new type of mechanical connector, referred to as "Cage Clamp", to enhance rebar cage stability and safety. Component-level experimental tests are conducted to determine the force-displacement response of Cage Clamp connectors for crossbar connections in different degrees of freedom. The results highlight the remarkable strength and stiffness of Cage Clamp connectors, significantly outperforming traditional tie-wire connections. Furthermore, full-scale experimental tests are performed on a circular underground pile-shaft rebar cage with Cage Clamp connectors to assess its behavior under various site handling conditions. The data obtained from these experiments are used to construct and refine detailed 3D finite element models of the rebar cages, capable of capturing the complex behavior of rebar cages with Cage Clamp connectors. Using the numerical model, a sensitivity analysis is performed to assess the effect of the number of Cage Clamps on the deflection and stability of the rebar cage. The findings show that using cage clamps to connect pick-up rebar with lateral reinforcement at every 8 to 10 feet is sufficient to ensure the stability of the cage during typical site handling conditions. The results of this study serve as a basis for establishing analysis, design, fabrication, and handling guidelines for rebar cages, contributing to safe and efficient construction practices.

In this review, we present the latest exclusion limits obtained with astroparticles for Lorentz Invariance Violation (LIV) in the photon sector. We discuss the techniques known as energy-dependent time delay or time lag, subluminal pair production threshold shift, superluminal photon decays and superluminal photon splitting. Perspectives for future results in LIV with the next generation of experiments are also addressed.

Structural health monitoring has been studied by a number of researchers as well as various industries to keep up with the increasing demand for preventive maintenance routines. This work presents a novel method for reconstruct prompt, informed strain/stress responses at the hot spots of the structures based on strain measurements at remote locations. The structural responses measured from usage monitoring system at available locations are decomposed into modal responses using empirical mode decomposition. Transformation equations based on finite element modeling are derived to extrapolate the modal responses from the measured locations to critical locations where direct sensor measurements are not available. Then, two numerical examples (a two-span beam and a 19956-degree of freedom simplified airfoil) are used to demonstrate the overall reconstruction method. Finally, the present work investigates the effectiveness and accuracy of the method through a set of experiments conducted on an aluminium alloy cantilever beam commonly used in air vehicle and spacecraft. The experiments collect the vibration strain signals of the beam via optical fiber sensors. Reconstruction results are compared with theoretical solutions and a detailed error analysis is also provided.

Background: This study stands as a pioneer in the histological evaluation of the biological behavior of a novel implant design featuring decompressive cervical blades. Hence, the aim of the present study was to evaluate the healing outcome in cortical regions at where decompressive protocols were adopted using implants equipped with blades. Materials and methods: Blades with varying diameters were integrated into the coronal portion of the implant to prepare the cortical region of rabbit tibiae. The blade diameters differed from the implant collar by the following amounts: control group (0 µm), +50 µm, and +200 µm. Results: No marginal bone loss was detected. Instead, all implants exhibited new bone formation in the coronal region. Complete closure was observed in the CG-0 group, as well as in the TG-50 and TG-200 groups, despite the presence of marginal gaps without primary bone contact at installation. In the apical region, most implants breached the cortical layer. Nevertheless, new bone formation in this region completely closed the osteotomy, effectively isolating the internal environment of the tibia from the external. Conclusions: The use of a blade attached to the implant body enabled precise preparation of the cortical layer, allowing for controlled decompression in the targeted area. This technique resulted in optimal osseointegration with no loss of marginal bone, and complete restoration of marginal gaps ranging from 0 µm to 200 µm.