The liver health of Gilthead sea bream and European sea bass fed fishmeal-free diets including various proportions of plant proteins, insect and poultry by-product meals, was investigated through biochemical and histological analyses using a new Liver Index (LI) formula. Four isoproteic (45% DM) and isolipidic (20% DM) diets were compared: a control, plant-based diet (CV) and other three test ones where 40% of a plant protein-rich ingredient mixture was replaced by Hermetia illucens (H40) or poultry by-product (P40) meals alone or in combination (H10P30). The trials lasted 12 and 18 weeks for sea bream and sea bass, respectively. The results so far ob-tained highlighted species-specific differences in the physiological response to dietary changes. In sea bream, the biochemical and histological responses suggest favorable physiological status and liver health, with higher serum cholesterol (CHO) and triglyceride (TAG) levels and moderate hepatocyte lipid accumulation with the H10P30 diet compared to CV (p<0.05). In sea bass, all diets resulted in elevated serum TAG levels and liver lipid accumulation particularly in fish fed the P40 one (p<0.05) which resulted in the highest LI, coupled with higher frequency of severe lipid accumulation, hypertrophy, cord loss, peripheral nuclei displacement and pyknosis. In conclusion sea bream well adapted to the test diets, while sea bass exhibited altered hepatic lipid metabolism leading to incipient liver steatosis, likely due to the high lipid content of the diets including the insect and poultry meals. The LI developed in this study proved to be a reliable tool for assessing the effects of dietary changes on liver health of sea bream and sea bass, consistent with biochemical and histological findings.

Background: Traumatic events adversely affect the clinical course of obsessive-compulsive disorder (OCD). Our investigation explores the correlation between prolonged interpersonal trauma and the severity of symptoms related to obsessive-compulsive and anxiety disorders. Methods: The study follows a cross-sectional and observational design, employing the International Trauma Questionnaire (ITQ) to examine areas linked to interpersonal trauma, the Hamilton Anxiety Rating Scale (HAM-A), and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to assess anxious and obsessive-compulsive symptoms, respectively. Descriptive analysis, analysis of variance (ANOVA), and logistic regression analyses were conducted. Results: We recruited 107 OCD-diagnosed patients, categorizing them into subgroups based on the presence or absence of complex post-traumatic stress disorder (cPTSD). The ANOVA revealed statistically significant differences between the two groups in the onset age of OCD (p=0.083), psychiatric familial history (p=0.023), HAM-A, and Y-BOCS (p=0.000). Logistic regression indicated a statistically significant association between the presence of cPTSD and Y-BOCS scores (p=0.000). Conclusion: The coexistence of cPTSD in OCD exacerbates obsessive-compulsive symptoms and increases the burden of anxiety. Further advancements in this field are crucial for mitigating the impact of early trauma on the trajectory of OCD and associated anxious symptoms.

In the literature, estimation of weighted extropy are least considered. In this paper some non parametric estimators of weighted extropy are given. The validation and comparison of the estimators are implemented with the help of simulation study and data illustration. The usefulness of the estimators are demonstrated using real data sets.

Recently, some authors have developed a shell-less culture system for chick embryos by using a plastic lm as culture vessels. We will show that velocity of rotation of vessels in incubator and temperature have direct relations with growth of chick embryos. We also obtain a mathematical relation between velocity, temperature and rate of growth of chick embryo.

Background. Pregnancy rates in women on dialysis have increased in the last decades, thus making it a topic of growing interest. The rarity of this event is predominantly due to fertility problems and to the high rates of pregnancy failure including stillbirth, fetal and neonatal deaths [1]. Methods. We conducted a narrative review of existent literature in order to analyse the major issues about pregnancy on dialysis to give the reader a full updated prospective about this topic which, even if not common, is becoming more and more frequent. Results. Even if recently acquired knowledge has improved diagnosis and treatment of dialysis pregnancies focusing on several aspects, pregnancy on dialysis remains a great challenge for obstetricians and should be managed by a multidisciplinary expertise team. Conclusion. Dialysis in pregnancy may be necessary for women previously affected by end stage renal disease (ESRD) becoming pregnant, or in case of acute renal injury presenting for the first time during gestation or, again in case of existent renal pathology worsening during pregnancy and requiring dialysis. Although some evidence suggests that more intensive dialysis regimens are correlated with better obstetric outcomes, the optimal therapeutic protocol still remains to be established.

Culture, gender and religion are closely linked each other’s, profoundly affect the role of each person within the Society, and also affect the ability to access to the health resources. We are now living a worldwide crisis due to the SARS-CoV-2 pandemic. In order to appropriately tackle it, an alliance between science, politics and citizens is needed. In this article, we summarize current evidences of how religions can represent, on one hand, a risk moment for spreading the virus (in relation with overcrowded events), on the other, a precious opportunity to engage people, and in particular minorities, in fighting the pandemic. To win this fight, we need a multicultural approach that takes into account every aspect of human life, and among these religion, which influences so much culture, everyday life and well-being.

In recent years, the production of renewable energy represents one of the main challenges of modern and future society. The new cultivation method called Agrivoltaic (hereafter AV), combines and associates agricultural production and renewable energy (photovoltaic) production in a collaborative synergy from which both benefit. In this study, the dry matter and essential oils yield of six medicinal species (Salvia officinalis L., Origanum vulgare L., Rosmarinus officinalis L., Lavendula angustifolia L., Thymus citriodorus L. and Mentha spicata L.) grown underneath a dynamic AV system in comparison to those in full sun (T), were evaluated. In particular, below the dynamic AV system, due to the rotation of the panels, two plot areas on the ground were distinguished: one always covered by the panels (UP), and another one covered alternatively (BP). During the aromatic crop cycles, the solar radiation, infrared leaf temperature and air temperatures in UP, BP and T plot, were measured. In addition, at harvest time, weed survey was carried out. The results showed that, in general, the solar radiation and infrared leaf temperature were lower in UP plot than in either the BP and T plots, while the air temperatures were similar in all compared plots. Also the weed cover percentage was lower in the UP plot than other ones. The essential oils yield in the sage, thyme, mint and rosemary plants were higher in both UP and BP plots than for T plot. Thus, shading and/or less weed infestation may have been the main factors favorably influencing the performance of medicinal crops under a dynamic AV system.

Microglial dysfunction is one of the hallmarks and leading causes of common neurodegenerative diseases (NDD), including Alzheimer’s disease (AD) and Parkinson’s disease (PD). All these pathologies are characterized by aberrant aggregation of disease-causing proteins in the brain, which can directly activate microglia, trigger microglia-mediated neuroinflammation, and increase oxidative stress. Inhibition of glial activation may represent a therapeutic target to alleviate neurodegeneration. Recently, 3-iodothyronamine (T1AM), an endogenous derivative of thyroid hormone (TH) able to interact directly with a specific GPCR known as trace amine-associated receptor 1 (TAAR1), gained interest for its ability to promote neuroprotection in several models. Nevertheless, T1AM’s effects on microglial disfunction remain still elusive. In the present work we investigated whether T1AM could inhibit the inflammatory response of human HMC3 microglial cells to LPS/TNFα or β-amyloid peptide 25-35 (Aβ25-35) stimuli. The results of ELISA and qPCR assays revealed that T1AM was able to reduce microglia-mediate inflammatory response by inhibiting the release of proinflammatory factors, including IL-6, TNFα, NF-kB, MCP1 and MIP1, while promoting the release of anti-inflammatory mediators, such as IL-10. Notably, T1AM anti-inflammatory action in HMC3 cells resulted to be a TAAR1-mediated response, further increasing the relevance of the T1AM/TAAR1 system in the management of NDD.

Guiding the visitor to appreciate the sights during an excursion is crucial to building a memorable experience. In the literature, we find many articles exploring the use of sophisticated technologies towards such a goal. The case of tourism proposals for inland areas exhibits a noteworthy aspect, since the presence of human artifacts and the signage may damage the experience, and introduce pollutants as well. This paper analyzes the signage for a natural trail putting into practice a holistic methodology that takes into account all aspects of the problem, starting from the touristic vocation of the area and the social fabric. The analysis indicates slow, community-involved tourism as the preferable target, with extreme requirements of sustainability in the social, economic, and environmental domains for the signage solution. Appropriate governance guidelines are given to implement the proposal. Footprint evaluations address the QR-code technology, which is used to design a real-scale solution finally deployed on the field.

Much evidence has accumulated over the past decade in favor of a significant association between dysbiosis, neuroinflammation and neurodegeneration. Presently, the pathogenetic mechanisms triggered by molecules produced by the altered microbiota, also responsible for the onset and evolution of Alzheimer Disease will be described. Our attention will be focused on the role of astrocytes and microglia. Numerous studies have progressively demonstrated how these glial cells are important to ensure an adequate environment for neuronal activity in healthy conditions. Furthermore, it is becoming evident how both cell types can mediate the onset of neuroinflammation and lead to neurodegeneration when subjected to pathological stimuli. Based on this information, the role of major microbiota products in shifting the activation profiles of astrocytes and microglia from a healthy to a diseased state will be discussed focussing on Alzheimer Disease pathogenesis.

Microturbines can be used not only in models and education but also to propel UAVs. However, their wider adoption is limited by their relatively low efficiency and durability. Validated simulation models are required to monitor their performance, improve their lifetime, and design engine control systems. This study aims at developing a numerical model of a micro gas turbine for prediction and prognostics of engine performance. To build a reliable zero-dimensional model, the available compressor and turbine maps were scaled to the available test bench data with the least squares method, to meet the performance of the engine achieved during bench and flight tests. A steady-state aeroengine model was implemented in GSP and compared with experimental operating points. The selected flight data was then used as input for the transient engine model. The exhaust gas temperature (EGT) and fuel flow were chosen as the two key parameters to validate the model, comparing the numerical predicted values with the experimental ones. The observed difference between the model and the flight data was lower than 3% for both EGT and fuel flow.

In recent years information and communication technologies (ICT) play a significant role in all aspects of modern society and impact socioeconomic development in sectors as education, administration, business, medical care and agriculture. The benefits of such technologies in agriculture can be appreciated only if farmers use them. In order to predict and evaluate the adoption of these new technological tools, the technology acceptance model (TAM) can be a valid aid. The paper measures the potential acceptance of an e-learning tool designed for EU farmers and agricultural entrepreneurs. Starting from a literature review of the technology acceptance model, by analyzing the most commonly used external variables in the fields of e-learning, Agriculture, and Virtual reality, the analysis shows that computer self-efficacy, individual innovativeness, computer anxiety, perceived enjoyment, social norm, content and system quality, experience and facilitating conditions are the most common determinants addressing technology acceptance. Furthermore, findings evidenced that the external variables have a different impact on the two main beliefs of the TAM Model, Perceived Usefulness (PU) and Perceived Ease of Use (PEOU). This study is expected to bring theoretical support for academics when determining the variables to be included in TAM extensions.

Introduction: The aim of the present systematic review was to evaluate the clinical and radiographic success of partial pulpotomies in deep caries processes or post-eruptive defects in young, vital permanent teeth. Methods: Electronic databases, PubMed, Scopus, and Embase, were searched, followed by a manual search. Randomized controlled trials evaluating partial pulpo-tomy with a follow-up period of ≥12 months were included. Meta-analyses using a random effect model were performed. Results: A total of 3.127 articles were retrieved, and after duplicate re-moval, 2.642 were screened by title and abstract; 1 additional article was found during the manual search in the reference lists, and 79 were identified. Finally, 6 papers were included in the review. Regardless of the partial pulpotomy modalities or material used, there were no signifi-cant differences between clinical and radiographic success rates (cumulative success rate 91,8%-92,3%, respectively). Five studies were included in the meta-analysis that did not indicate any statistically significant differences in success rates when Mineral Trioxide Aggregate was compared to other materials (95% CI 0,239 to 1,016 p=0.055). Conclusion: This research system-atically evaluates the evidence and summarises the available data on partial pulpotomy in young permanent teeth. Given its high clinical and radiographic success rate, partial pulpotomy should be considered when vital pulpal therapy needs to be performed in highly damaged young per-manent teeth, as this procedure provides a biological benefit and allows more invasive endodon-tic treatments to be postponed.

Background and objectivesː Physical examination is the predominant method for evaluating pelvic floor defects. Magnetic Resonance Imaging (MRI) is a radiological technique useful to identify the underlying defects of pelvic floor structures that require surgery. The primary aim was to find correspondence between the clinical and radiological staging of pelvic organ prolapse (POP) before and after vaginal surgery. A secondary endpoint was to investigate, through clinical and MRI findings if surgery influences continence mechanisms. Finally, we reported changes in the quality of life in women who underwent surgery for prolapse. Materials and methodsː Twenty-five women with prolapse stage ≥ 2 POP-Q were recruited in this prospective study. They underwent preoperative clinical examination, MRI at rest and under the Valsalva maneuver, and quality of life questionnaires. Three months after vaginal surgery they repeated clinical and radiological evaluation. Resultsː Twenty women completed the study. Both clinical and MRI evaluations showed an improvement in prolapse and symptoms after surgery. There were some discrepancies between clinical and radiological staging. MRI parameters did not show differences between pre and postoperative at rest; under the Valsalva maneuver instead, the measurements changed after surgery. Continence was not worsening by the widening of the vesicourethral angle. Patients reported improvement in quality of life. Conclusionsː MRI is an accurate and objective method to define the stage of prolapse but the clinical evaluation alone is sufficient to stage prolapse before surgery and evaluate the result at follow-up. It is an accurate method to visualize some pelvic structures that can be compromised because of pelvic organ prolapse. MRI showed that vaginal surgery doesn’t affect continence mechanisms.

Distinctive strains of Pantoea are used as soil inoculants for their ability to promote plant growth. Pantoea agglomerans strain C1, previously isolated from the phyllosphere of lettuce, can produce indole-3-acetic acid (IAA), solubilize phosphate, and inhibit plant pathogens, such as Erwinia amylovora. In this paper, the complete genome sequence of strain C1 is reported. In addition, experimental evidence is provided on how the strain tolerates arseniate up to 100 mM, and on how secreted metabolites like IAA and siderophores act as biostimulants in tomato cuttings. The strain has a circular chromosome and two prophages for a total genome of 4,846,925-bp, with a GC content of 55.2%. Genes related to plant growth promotion and biocontrol activity, such as those associated with IAA and spermidine synthesis, solubilization of inorganic phosphate, acquisition of ferrous iron, and production of volatile organic compounds, siderophores and GABA, were found in the genome of strain C1. Genome analysis also provided better understanding of the mechanisms underlying strain resistance to multiple toxic heavy metals and transmission of these genes by horizontal gene transfer. Findings suggested that strain C1 exhibits high biotechnological potential as plant growth-promoting bacterium in heavy metal polluted soils.

Exploring the contribution of proximal family risk factors on SLC6A4 DNA methylation in children with a history of maltreatment

The developmental phase of adolescence is characterized by a multitude of neurocognitive and psychosocial changes and is therefore considered one of the most critical developmental periods of life. Experimentation on the use of substances often begins in adolescence and so does the addiction process. Most research in human subjects shows that chronic cannabis abuse is the cause of the impairment of some cognitive functions, affecting the performance on divided attention, verbal memory and working memory. In this study, we wanted to investigate how the abuse of cannabis (chronic, occasional and absence use) can influence global cognitive functioning, also through executive functions. From the statistical analyzes of our study, it emerges that the group of subjects who use chronic cannabis (group 1) has a significant drop in working memory tasks compared to the group that does not use it (group 3). In addition, the goal of future studies by our group is to verify the permanent alteration of cognitive processes affected through revaluations with calendar follow-up (controlled).

Background: Infantile tibia vara (ITV) is a rare proximal tibia deformity in infancy, leading to progressive knee varus. High tibial osteotomy is commonly practiced but has high recurrence rates. This study analyzed factors affecting treatment failure and recurrence in children undergoing opening-wedge high tibial osteotomy (OWHTO) for ITV. Methods: We retrospectively studied children with ITV who had OWHTO with press-fit cancellous bone allograft between 2000 and 2020, with ≥2-year follow-up. Outcomes included recurrence (knee varus with tibiofemoral angle >10°), complications, and reintervention. Results: We analyzed 39 knees in 29 patients (mean age: 4.8 ± 1.9 years; median follow-up: 7.4 years). Recurrence occurred in 22 cases (56%). Age at surgery significantly influenced recurrence, with rates of 16% before age 5 versus 95% later (hazard ratio: 12.0, p = 0.001). Langenskiöld stage also affected recurrence (β-coefficient: 2.7, 95% C.I. 1.0–4.5, p = 0.002; pseudo-R-squared: 0.50, p = 0.001), with recurrence in all stage III IV or higher cases. Conclusions: Early diagnosis and treatment before age 45, ideally with Langenskiöld stage III or lower, are crucial for stable correction with OWHTO alone. Late, high-grade ITV may require combined, acute or gradual, and/or staged correction. Further evidence is needed for optimal management.

The role of epigenetic alterations in the pathogenesis of age-related macular degeneration (AMD) has been pending so far. Our study investigated the effect of oxidative stress and inflammation on DNA methyltransferases (DNMTs) and Sirtuin 1 (SIRT1) functions, as well as on long interspersed nuclear element-1 (LINE-1) methylation, in human retinal pigment epithelial (ARPE-19) cells. Therefore, we evaluated whether treatment with resveratrol may restore changes in LINE-1 methylation by modulating DNMTs and SIRT1 functions. Cells were treated with 25 mU/ml glucose oxidase (GOx) or 10 µg/ml lipopolysaccharide (LPS) to mimic oxidative or inflammatory conditions, respectively. Oxidative stress decreased DNMT1, DNMT3a, DNMT3b and SIRT1 expression (p-values <0.05), as well as total DNMTs (-28.5%; p<0.0001) and SIRT1 (-29.0%;p<0.0001) activities. Similarly, inflammatory condition decreased DNMT1 and SIRT1 expression (p-values<0.05), as well as total DNMTs (-14.9%;p=0.007) and SIRT1 (-20.1%;p<0.002) activities. Interestingly, GOx- and LPS-treated cells exhibited lower LINE-1 methylation compared to controls (p-values<0.0001). We also demonstrated that treatment with 10 μM resveratrol for 24 hours counteracted the detrimental effect on LINE-1 methylation via increasing DNMTs and SIRT1 functions in cells upon oxidative and inflammatory conditions. However, further studies should explore the perspectives of resveratrol as a suitable strategy for the prevention and/or treatment of AMD.

This study investigates the environmental parameters contributing to the Urban Heat Island (UHI) effect in historically built environments, focusing on Matera's Street Canyon. The primary objective is to enhance understanding of heritage centers' ecological sustainability and management frameworks. The study involves two main phases: the initial research and development phase, including a comprehensive literature review and methodology development, followed by the empirical data gathering and analysis phase, utilizing advanced techniques such as 3D laser scanning, satellite imagery, and meteorological data integration. Key findings reveal significant correlations between urban morphology, material properties, and UHI intensity, suggesting stra-tegic urban planning interventions to mitigate UHI effects. This research provides actionable in-sights for urban planners and policymakers, emphasizing the importance of balancing heritage preservation with modern sustainability needs.

Micro turbojets are used for propelling radio-controlled aircraft, aerial targets and personal air vehicles. When compared to full-scale engines, they are characterized by relatively low efficiency and durability. In this context, the degraded performance of gas path components could lead to an unacceptable reduction in the overall engine performance. In this work, a data-driven model based on a conventional Artificial Neural Network (ANN) and an extreme learning machine (ELM) was used for estimating the performance degradation of the micro turbojet. The training datasets containing the performance data of the engine with degraded components were generated using the validated GSP model and the Monte Carlo approach. In particular, compressor and turbine performance degradation were simulated for three different flight regimes. It was confirmed that component degradation had a similar impact in flight than at sea level. Finally, the datasets were used in the training and testing process of the ELM algorithm with four different input vectors. Two vectors had an extensive number of virtual sensors, and the other two were reduced to just fuel flow and Exhaust Gas Temperature. Even with the small number of sensors, the high prediction accuracy of ELM was maintained for takeoff and cruise but was slightly worse for variable flight conditions.

Background: In the last years, many new treatment options have widened the therapeutic scenario of genitourinary malignancies. Immunotherapy has shown efficacy, especially in the urothelial and renal cell carcinomas, with no particular relevance in prostate cancer. However, despite the use of immune checkpoint inhibitors, there is still high morbidity and mortality among these neo-plasms. Cancer vaccines represent another way to activate the immune system. We sought to summarize the most recent advances in vaccine therapy for genitourinary malignancies with this review. Methods: We searched Pubmed, Embase and Cochrane Database for clinical trials conducted in the last ten years, focusing on cancer vaccines in the prostate, urothelial and renal cancer. Results: Various therapeutic vaccines, including DNA-based, RNA-based, peptide-based, dendritic cells, viral vectors, and modified tumor cells, have been demonstrated to induce specific immune responses in a variable percentage of patients. However, these responses rarely corresponded to significant survival improvements. Conclusions: Further pre-clinical and clinical studies will improve the knowledge about cancer vaccines in genitourinary malignancies to optimize dosage, select targets with a driver role for tumor development and growth, and finally overcome resistance mechanisms. Combination strategies represent possibly more effective and long-lasting treatments.

Burn patients still represent an important challenge in critical care medicine today. These patients can develop significant neurological conditions up to intracranial hypertension, but as they find themselves hospitalized outside of neurocritical care and are often subjected to sedation for the complex management, they are sometimes underestimated. The aim of this study is to evaluate the feasibility of non-invasive methods for the early diagnosis of intracranial hypertension in these patients. In this prospective observational study, adult burn patients admitted to intensive care within the first 8 hours of the event were enrolled. These patients were studied through ultrasound measurement of optic nerve sheath diameter and intracranial vessel velocimetry with transcranial Doppler. In the 20 patients studied, no frankly pathological values were identified in the 3 different measurement stages (within 8 hours of the burn, then at 48 and 96 hours) and no correlations were identified between the measured values and the extension of the burn with the related risk of mortality. However, this study, one of a kind, demonstrates that these non-invasive methods are applicable to this specific patient population, and can represent an effective method for reducing the incidence of complications that are dangerous for survival.

Pregestational diabetes mellitus, if not well controlled, determines maternal and fetal complications. According to the new diagnostic criteria for gestational diabetes the diagnosis of diabetes mellitus can also occur in early pregnancy (overt diabetes ).The aim of this study was to determine pregnancy outcomes in women with overt type 2 diabetes. In this retrospective study we selected women with type 2 diabetes, pregestational or overt diabetes, who had at least one pregnancy followed in the period 2010-2022 at the Diabetic Care Unit of Padova.We analyzed 83 pregnancies in 68 diabetic patients; overt diabetes was diagnosed in 21,7% of pregnancies . 95% of patents with overt diabetes was immigrate . None of patients with overt type 2 diabetes planned their pregnancy, while pregnancy was planned in 26,3% of patients with pregestationalType 2 diabetes. Pre-pregnancy and first trimester glycemic control was worst in patients with overt diabetes(HbA1c 9.7± 3.1% vs 7.3% ± 2.3%, p< 0.044 at first visit; 8.1±1.9%, and 7.0±1.6%, p< 0.037 in the first trimester) with respect to type 2 diabetic mothers.As for maternal outcomes, 16,6% of pregnancy ended in miscariage and 5,5% of women developed gestational hypertension . 16,6% of newborn were LGA and 11,1% were affected by congenital anomalies. The high rate of congenital malformations in overt diabetes pregnancies is probably due to the worse metabolic control during the first trimester of pregnancy, when the organogenesis of the fetus takes place. So it is essential to identify these patients in the preconception phase so they can conceive in good glycemic control.

Sulfenic acids as small molecules are too unstable to be isolated and their transient nature offers the possibility to involve them in concerted processes that lead to the obtainment of functional groups such as sulfoxides, sulfones and disulfides. All these functions are present in a number of natural and synthetic drugs and can represent structural motives inducing biological relevant properties. In this small review the generation and reactions of sulfenic acid bearing naturally occurring residues are described. Carbohydrate and aminoacid-derived sulfenic acids have been used in concerted addition to triple bonds to obtain alliin derivatives and thiosugars in enantiomerically pure form. Glycoconjugates with sulfinyl, sulfonyl and disulfane functional groups and pyridine-derived disulfides have been obtained from bis and tris-sulfinyl precursors of sulfenic acids. Small families of such compounds have been subjected to preliminary biological tests. Starting from the evidence that the control of molecular architecture and the presence of suitable functional groups can play a significant role on the exhibition of biological properties, apoptotic effects on malignant cells by glycoconjugates and inhibitory activity against the important human pathogen S. aureus by pyrimidine-derived disulfides have been found.

The edible portion of Cannabis sativa L. are the seeds. The seeds are generally used for the production of hemp oil, appreciated for the high percentage of α-linolenic acid. The waste obtained after seeds oil extraction, reduced in fine powder, is the subject of this study. Since hemp seeds are considered to be a source of many valuable bioactive compounds, the addition of hemp seed flour to durum wheat for making fortified bread could have an effect on the health of consumers. The aim of this study was to use variable percentages of hemp seed flour for the production of bread, and to determine the fortification impact on chemicals, texture, organoleptic characteristics, crumb color, changes in crumb texture, total polyphenols, free radical scavenging activity and amino acids contents. The rheological and chemical qualities of bread samples, obtained by using a durum wheat cultivar Ciclope fortified with defatted hemp seeds flours, were evaluated. The solid residue left after the extraction of the oil from seeds (generally thrown away as waste or added to feed) was shredded and sieved at 0.530 mm (Hemp 1) or 0.236 mm (Hemp 2). Samples of fortified breads were obtained by substitution of variable percentages of durum wheat flour with the two hemp flours (5%, 7.5%, and 10%). Fortified bread’s total phenolic content was in a range of 0.73±0.017 and 1.73±0.029 mg GAE/g and an-ti-radical scavenging activity was included in the range from 1.17±0.099 and 3.18±0.071mmol TEAC/100g, according to the increasing fortification. Comparison between bread made with Ciclope semolina and hemp flour fortified breads, showed a large increase in amino acid content in fortified samples ones. In particular, bread fortified with 10% Hemp 2 flour highlights a greater content of glutamic acid, tyrosine, proline and essential amino acids such as leucine and isoleucine, compared to the other samples with same percentage of substitution. The amount of hemp seed flour influenced the color of the crumb by increasing the yellow index from 18.24 (100% Ciclope) to 21.33 (bread with Hemp 2 flour at 5%).

Background: Cell-free plasma DNA (cfDNA) is composed of circulating extracellular DNA originating from apoptosis or cell necrosis. It is generally present in healthy individuals, but its levels increase in different clinical conditions, such as kidney disease, sepsis, myocardial infarction, trauma and cancer. Caspase-3 plays a central role in apoptosis, a mechanism of programmed cell death involved in the pathogenesis of chronic kidney disease (CKD). Methods: We compared cfDNA and caspase-3 levels in 25 CKD patients and in 10 healthy subjects, evaluating the modification of their concentrations according to CKD stage. We also analyzed the correlation between cfDNA and caspase-3 levels in CKD patients and the correlation between cfDNA and caspase-3 levels and creatinine and urea. Results: CfDNA and caspase-3 levels were higher in CKD patients compared to healthy subjects, in particular in patients with advanced renal disease. A positive correlation between cfDNA and caspase-3 levels and between cfDNA and caspase-3 and creatinine and urea was also observed. Conclusion: Patients with chronic kidney disease present higher levels of cfDNA and caspase-3 levels compared with healthy subjects. The worsening of renal damage and the increase in uremic toxin concentration are associated to higher levels of cfDNA and caspase-3 levels, thus reflecting a central role of apoptosis in the pathogenesis of CKD.

Background: The management of penile cancer patients has some grey zones, one of them being the timing of prophylactic pelvic lymph node dissection. Here, we review the impact of timing of prophylactic inguinal and pelvic lymph node dissection on patients’ outcome. Methods: Relevant databases were searched according to recommendations by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Before the systematic review we present a narrative review on the indications for lymph node dissection and the impact of pathological anatomical considerations on the timing of prophylactic lymph node dissection and patients’ outcome. The primary research questions were disease-free and overall survival rate in patients who underwent early or late lymph node dissection after penile cancer diagnosis. Results: Four clinical trials were included in the systematic review. Conclusions: The survival rate of patients with penile cancer is strictly associated with the timing of prophylactic pelvic lymph node dissection. Even though there are no randomized controlled trials we conclude that there is evidence for a strong recommendation that lymph node dissection should be performed as soon as possible after diagnosis with3 months as a realistic cut-off time between early and late. According to the present evidence base, lymph node dissection should be offered the sooner the better to all patients at high risk of lymph node metastasis.

Recently, pharmaceutical research has been focused on the design of new antibacterial drugs with higher selectivity towards several strains. Major issues concern the possibility to obtain com-pounds with fewer side effects, at the same time effectively overcoming the problem of antimi-crobial resistance. Several solutions include the synthesis of new pharmacophores starting from piperazine or morpholine core units. Mass spectrometry-based techniques offer important sup-port for the structural characterization of newly synthesized compounds to design safer and more effective drugs for various medical conditions. Here, two new piperazine derivatives and four new morpholine derivatives were synthesized and structurally characterized through a combined approach of FT-ICR and LTQ mass spectrometry. The support of both high-resolution and low-resolution mass spectrometric data namely accurate mass measurements, isotopic distribu-tion and MSn spectra, was crucial to confirm the success of the synthesis. These compounds were further evaluated for inhibitory activity against a total of twenty-nine Gram-positive and Gram-negative bacteria to determine the action spectrum and the antimicrobial effectiveness. Results demonstrated compounds’ antimicrobial activity against many tested bacterial species, providing an inhibitory effect linked to different chemical structure and suggesting that the new-synthesized derivatives could be considered as promising antimicrobial agents.

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

Background: Lower limb length discrepancy (LLD) in children and adolescents, often due to congenital or acquired conditions, is treated to achieve limb equality and alignment, optimizing function and minimizing cosmetic concerns for an active adulthood. This study evaluated the Health-Related Quality of Life (HRQoL) and physical functioning of adults who underwent unilateral limb lengthening with circular external fixators (EFs) in childhood. Methods: Fifty patients treated at a median age of 14.9 years completed the Short Form 36 (SF-36) and Stanmore Limb Reconstruction Score (SLRS) questionnaires in adulthood, with a median follow-up of 8.9 years. Results: Among the 50 patients, 38 underwent a single limb lengthening (21 tibia, 12 femur, 5 both), while 12 required multiple cycles. The median residual LLD was 0.4 cm, with 12 patients (24%) having over 2 cm. Complications occurred in 67% of procedures, mainly due to prolonged healing. Physical and mental health scores were significantly lower than normative data. The mean Physical Component Summary was 52.2 ± 7.2 (p = 0.20). The mean Mental Component Summary was 43.9 ± 8.6 (p = 0.001), notably lower in congenital LLD cases. Many SLRS items (Pain, Social, Physical Function, Work, and Emotions) strongly correlated with SF-36 items. Conclusions: The study highlights the challenges in treating LLD, emphasizing the significant mental health impact, especially in congenital cases, and the necessity for comprehensive long-term care strategies. These findings suggest that future therapeutic strategies should focus on both physical and psychological outcomes to improve overall recovery in LLD treatment.

In January and February 2001, El Salvador was hit by two strong earthquakes that triggered thousands of landslides, causing 1,259 fatalities and extensive damage. The analysis of aerial and SPOT-4 satellite images taken a few days after the events allowed us to map 6,491 coesismic landslides, which occurred in 14 study areas extending for about 400 km2. Four different Multivariate Adaptive Regression Splines (MARS) models were produced by using different covariate sets and landslide inventories, the latter containing the slope failures triggered by an extreme rainfall event of November 2009 and those induced by the earthquakes of 2001. Moreover, two validation scenarios were employed, including the 25% and 95% of the mapped landslides, respectively. The results of our experiment revealed that: (i) MARS algorithm provides reliable predictions of coesismic landslides; (ii) models calibrated with rainfall-induced landslides predict with acceptable accuracy landslides caused by deep earthquakes and distributed over vast areas; (iii) the best accuracy is achieved by models trained with both preparatory and trigger variables; (iv) a small portion of the landslides produced by an earthquake can be used to calibrate MARS predictive models that help to identify slopes where yet unreported landslides may have occurred.

Background: Permanent tracheostomy because of total laryngectomy surgery entails great conse-quences for the patient regarding respiratory physiopathology such as the filtering, humidifying, and heating function of the air by the nose is lost. The use of special stomal filters can determine adequate protection of the trachea-broncho-pulmonary system with a reduction in respiratory pathologies. In fact, in most cases laryngectomee patients are first cigarette smokers who for this reason already have also respiratory diseases such as chronic obstructive pulmonary disease (COPD). Despite the availability of tracheal filters, multiple times, as reported in the literature, the patient tends to limit their use due to reported breathing difficulties, especially in conditions of intense breathing. Methods: The objective of this clinical study was to evaluate the most suitable stomal filter for the laryngectomee patient during physical activity. The filters studied were an INHEALTH device (Blom-Singer SpeakFree HME); two ATOS devices (Provox® Life™ Energy HME and Provox® Life™ Home HME); and an FAHL device (Laryvox HME Sport). Results: For this purpose, the performances of 31 laryngectomee patients, subjected to medi-um-high physical effort, were analyzed through a standardized pneumological test, the Six Minute Walking Test (6MWT) which involves a sustained walk lasting six minutes, with evaluation , every 60 seconds, heart rate, oxygen saturation and meters travelled; furthermore, it examines two sub-jective indices, namely, the basal and final dyspnea index and the initial and final muscular fatigue index.

Between October 2021 and April 2022, 317 outbreaks caused by highly pathogenic avian influen-za (HPAI) H5N1 viruses were notified in poultry farms in the northeastern Italian Regions. The complete genomes of 214 strains were used to estimate the genetic network based on the virus similarity. An exponential random graph model (ERGM) was used to assess the effect of at-risk contacts, same owners, in-bound/out-bound risk windows overlap, genetic differences, geograph-ic distances, same species and poultry company, on the probability of observing a link within the genetic network, which can be interpreted as the potential propagation of the epidemic via lateral spread or a common source of infection. The variables same poultry company (Est.=0.548, C.I.=[0.179;0.918]) and risk windows overlap (Est.=0.339, C.I.=[0.309;0.368]) were associated with a higher probability of link formation, while the genetic differences (Est.=-0.563, C.I.=[-0.640;-0.486]) and geographic distances (Est.=-0.058, C.I.=[-0.078;-0.038]) indicated a re-duced probability. The integration of epidemiological data with genomic analyses allows moni-toring the epidemic evolution and helps explain the dynamics of lateral spreads suggesting the potential diffusion routes. The 2021-2022 epidemic stresses the need to further strengthen the bi-osecurity measures, and to encourage the reorganisation of the poultry production sector to mini-mize the impact of future epidemics.

Parkinson's disease (PD) stands as the most prevalent degenerative movement disorder, characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. In this study, we assessed the transcriptome by analyzing post-mortem mRNA extracted from the substantia nigra of individuals with PD and healthy controls. A total of 16,148 transcripts were identified, with 92 mRNAs displaying differential expression between PD and control groups. Specifically, 33 mRNAs were significantly upregulated, while 59 mRNAs were downregulated in PD compared to controls. The identification of statistically significant signaling pathways, with an adjusted p-value threshold of 0.05, unveiled noteworthy insights. Particularly, enriched categories included cardiac muscle contraction (involving genes such as ATPase Na+/K+ transporting subunit beta 2 (ATP1B2), solute carrier family 8 member A1 (SLC8A1), and cytochrome c oxidase subunit II (COX2)), GABAergic synapse (involving GABA type A receptor-associated protein like 1 (GABARAPL1), G protein subunit beta 5 (GNB5), and solute carrier family 38 member 2 (SLC38A2)), autophagy (involving GABARAPL1 and tumor protein p53-inducible nuclear protein 2 (TP53INP2)), and Fc gamma R-mediated phagocytosis (involving amphiphysin (AMPH)). These findings uncover new pathophysiological dimensions underlying PD, including the involvement of cardiac muscle contraction and specific mitochondrial activity. This knowledge not only contributes to better diagnostic precision but also paves the way for the development of new targeted therapies.Keywords: mRNAs; RNA sequencing; Parkinson’s disease; transcriptome analysis; substantia nigra

Introduction: The aim of this study was to prospectively evaluate parents’/guardians’ late recall of surgical procedures and risks of elective surgery after pre-operative interview with surgeons. Materials and Methods: All parents/guardians of patients <18 years of age undergoing elective procedures from January 15th to September 1st, 2022, were prospectively enrolled in the study. Before discharge, parents/guardians were asked to complete a questionnaire regarding the duration of the consent procedure, duration of the interview, quality of the informative handouts, and their ability to recall the type of disease, type of surgical procedure, and surgical risks. Answers were graded from 1 to 4. Results: One hundred and two questionnaires were returned. In all cases, informed consent was obtained between 24 and 72 hours prior to surgery. The following responses were collected: 98/102 (96%) parents/guardians reported that the duration of the consent process was adequate; 95/102 (93%) reported that the handouts were fully informative, and 7/102 (7%) reported that they were partially informative regarding explanation of the disease and surgical procedure; regarding complications, 93/102 (91%) perceived the handouts to be fully/partially informative, while 4/102 (4%) perceived the handouts to be poorly/non-informative, and 5/102 (5%) did not provide a response; 94/102 (92%) stated that they remembered the pathology, but only 87/94 (93%) recalled it correctly; 90/102 (88%) stated that they remembered the type of procedure, but only 76/90 (84%) recalled it correctly; and 53/102 (52%) stated that they remembered the surgical risks, but only 20/53 (38%) could recall more than one complication. Conclusions: Late recall of surgical complications by parents was poor despite the high perceived quality of the surgical risk handouts and medical interview.

The onset and progression of the salivary and gut microbiota, the transmission and the impact of the salivary microbiota on the development of early fecal microbial communities was herein explored. We characterized the microbiota of 82 faecal and 80 salivary samples, collected from 82 healty newborns at birth, 7, 15, 30, 90 and 180 days of life, by 16S rRNA targeted-metagenomics approach. Correlation heat-maps and co-occurrence networks were used to investigate microbial taxa relationship in saliva, gut and between the two ecosystems. In saliva microbiota, Streptococcus and Staphylococcus appeared as early commensals, dominating this ecosystem through the time, while Fusobacterium, Prevotella, Porphyromonas, Granulicatella and Veillonella were late colonizers. anaerobes as Enterobacteriace, Staphylococcus and Streptococcus, were gut microbiota pioneers, followed by the anaerobic Bifidobacterium, Veillonella, Eggerthella and Bacteroides. Streptococcus, Staphylococcus and Veillonella were shared by gut and saliva ecosystems (core microbiota). Early saliva and gut microbiota seem to evolve independently driven by local adaptation strategies, with the only exception for the oral Streptococcus and Veillonella genera, involved in gut microbiota development as seeding species. A more comprehensive knowledge of how oral microbiota may impact pathophysiological conditions of gut microbiota may open new avenues on the design of postbiotics.

The concept of vulnerable carotid plaques is pivotal in understanding the pathophysiology of is-chemic stroke secondary to large-artery atherosclerosis. At the macroscopic evaluation, vulnera-ble plaques are characterized by one or more of the following features: microcalcification, neo-vascularization, lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), thin fibrous caps, plaque surface ulceration, huge dimension determining stenosis, and plaque rupture. Recognizing these macroscopic characteristics is crucial to estimating the risk of cerebrovascular events, also in case of non-significant (less than 50%) stenosis. Inflammatory biomarkers, such as cytokines and adhesion molecules, lipid-related markers like oxidized low-density lipoprotein (LDL), and proteolytic enzymes capable of degrading extracellular matrix components are among the key molecules that will be scrutinized for their associative roles in plaque instability. Through their quantification and evaluation, these biomarkers reveal intricate molecular cross-talking govern-ing plaque inflammation, rupture potential, and thrombogenicity. Current evidence demonstrates that plaque vulnerability phenotypes are multiple and heterogeneous and are associated with as many highly complex molecular pathways that determine the activation of an immune-mediated cascade that culminates in thromboinflammation. This narrative review provides a comprehen-sive analysis of current knowledge on molecular biomarkers expressed by symptomatic carotid plaques. It explores the association of these biomarkers with the structural and compositional at-tributes that characterize vulnerable plaques

Time estimation was investigated in 24 healthy adults, 12 women and 12 men, before and after an exhaustive exercise. We compared the capability of estimating time intervals in the range from 1 to 5 s using tasks requiring mental count and tasks that did not allow the mental count. Time estimation and blood lactate levels were evaluated before and at the end of the exercise. We found that the perception of time intervals between 1 and 5 s was affected at the end of the exercise. The observed effects, associated with a significant increase in blood lactate levels, were different in the two types of time estimation used in the present study. In experimental conditions in which participants had to evaluate duration of the time interval by mental counting, at the end of exercise a significant reduction in the overestimation of time made at rest was observed. On the other hand, when participants had to assess the difference in duration between two events without the possibility to mentally count, at the end of the exercise a significant deterioration in performance was observed. In both cases, no gender differences were seen.

Optical forces are used to aggregate plasmonic nanoparticles and create SERS-active hot spots in liquid. When biomolecules are added to the nanoparticles, high sensitivity SERS detection is accomplished. Here we tailor this methodology to detect catalase and hemoglobin, two Raman resonant biomolecules, at concentrations down to 10 nM and 1 pM. Subsequently, we study the SERS signal in Bovine Serum Albumin as a function of the concentration, finding a monotonic dependence that suggests the possibility of quantitative detection. Finally, by exploiting nanoparticles functionalized with specific aptamers, we obtain first results on the SERS detection of Ochratoxin A, a fungal toxin found in food commodities and wine. This represents a first step towards the addition of molecular specificity to this novel biosensor strategy.

PURPOSE: The aim of this study was to identify the incidence of early mechanical failure in the first post-surgical year in patients who had undergone spinal surgery, and to assess the related risk factors. METHODS: Retrospective observational study of a prognostic cohort was conducted at an orthopaedic hospital, examining all patients with spine degenerative disease who consecutively underwent arthrodesis surgery between March 2018 and March 2019. The incidence of postoperative mechanical failure during the first year was calculated as primary outcome; the time between the date of the implant surgery and diagnosis of the mechanical failure was calculated as secondary outcome. RESULTS: A total of 237 patients were identified for statistical analysis. The median age of the group of patients was 47 years (IQR of 44), and 66.6% were female. The incidence of mechanical failure in the first postoperative year was 5.1% overall with 12 events and the median time between surgery and the need for revision surgery was 5 months (IQR=7.75). ASA score (OR= 2,39; p=0.134), duration of the surgical procedure (OR=1,27; p=0,006) and inability to walk at discharge (OR=7,86; p=0,072) were independent risk of factor associated with the mechanical failure. CONCLUSION: Higher ASA score and longer duration of surgery are risk factors for mechanical failure in the first year in patients who had undergone spinal surgery and must be carefully considered when planning spinal surgery. During hospitalization, recovery of ambulation must be encouraged to prevent mechanical failure. All these factors are useful in identifying patients with a closer follow-up is needed.

Background: Galectin-3 (Gal-3) overexpression is associated with fibroblastic proliferation and the production of collagen, resulting in increased cardiac fibrosis and remodelling. Aim of the study was to investigate on the expression of Gal-3 in hypertrophic hearts. We examined 19 surgical specimens taken from interventricular septum of 8 patients with Tetralogy of Fallot, 4 patients with aortic valve stenosis, 1 cardiac explant affected from dilated cardiomyopathy, and 6 myocardial biopsies of patients submitted to heart transplantation. Methods: All the samples were routinely processed, stained with Hematoxylin-Eosin, Trichromic stain and elastic fiber stain and selected by having the morphological features of myocardial hy-pertrophy: myocytolysis, nuclear pleomorphism, interstitial fibrosis. Results: At immunohistochemistry, myocardial fibers showed cytoplasmic expression of Gal-3 in the 4 patients with aortic valve stenosis (diffuse in 3 and mild in 1), in the 1 patient with cardiac explant (mild) and in the 4/6 transplanted hearts (mild and focal in 3 and diffuse in 1). The 8 patients affected from Tetralogy of Fallot and 2 patients with transplanted hearts resulted negative. Conclusions: The results agreed with the hypothesis that Gal-3 may play a role in cardiac hyper-trophy; its expression in myocardial fibers is not related with the morphological aspects as suggested by the absence in pediatric cases. The presence in myocardial biopsies taken from transplanted hearts would suggest a possible role in predicting clinical outcome of such patients.

Background: Over the past decade, the use of digital tools has grown and research evidence suggests that traditional media and new media offer both benefits and health risks for young children. The abilities to understand and use language represent two of the most important competencies developed during the first 3 years of life through the interaction of the child with people, objects, events, and other environmental factors. The main goal of our study is to evaluate the relationship between digital devices use and language abilities in children between 8-36 month, considering also the influence of several variables. Materials and Methods: We conducted a cross-sectional observational study on 260 healthy children (140 males = 54%) aged between 8-36 months (mean=23.5±7.18 months). All the parents completed a self-report questionnaire investigating the use of digital devices by their children, and a standardized questionnaire for the assessment of language skills (MacArthur). Multiple linear regression was used to evaluate the relationship between different variables. Subsequent moderation analysis were performed to verify the influence of other factors. Results: W found a statistically significant negative correlation between the total daily time of exposure to digital devices and the Actions and Gestures Quotient (ß=-0.397) in children between 8-17 months, and between the total daily time of exposure to digital devices and Language Quotient (ß=-0.224) in children between 18-36 months. Sex, level of education/job of parents, modality of use/content of digital device do not significantly affect these relationships. Conclusion: In our study we found that a longer time of exposure to digital devices was related to lower mimic-gestural skills in children from 8-17 months and to lower language skills in children between 18-36 months, regardless of age, sex, socio-economic status, content and modality of use. Further studies are needed to confirm and better understand this relationship, but parents and pediatricians are advised to limit the use of digital devices by children and encourage the social interaction to support the learning of language and communication skills in this age group.

Background: Pediatric obesity treatment is based on high-intensity lifestyle counseling. However, high dropout rates and low effectiveness have been reported even in specialized centers. Mobile health technologies have been used in research settings to overcome these limits with contrasting results. This study aims to evaluate the effectiveness of a six-month intervention with a mobile app for the treatment of pediatric obesity at 6 and 12 months of follow-up. Methods: Patients were randomly assigned to standard care or standard care plus mobile app (2:1). The mobile app delivered high-intensity lifestyle counseling for diet and physical activity. Results: Seventy-five subjects were prospectively enrolled. At six months of follow-up, the m-app group showed significantly lower dropout rates compared to standard care(p=0.01). The risk of dropout was significantly higher in controls compared to the intervention group (OR 3.86,95%C.I. 1.39-10.42,p=0.01). After one year of follow-up, we observed lower albeit non statistically significant dropout rates in the m-app compared to the standard care group(p=0.24). No differences were observed in terms of z-score BMI and percentage of BMI reduction between the two groups. Conclusion: our findings suggest that mobile app might help in the clinical management of children and adolescents with obesity in terms of dropout reduction.

Seismic monitoring in areas where induced earthquakes could occur is a challenging topic for seismologists due to generally very low signal to noise ratio. Therefore, the seismological com-munity is devoting several efforts to the development of high-quality networks around the areas where fluid injection and storage and geothermal activities take place, also following the national induced seismicity monitoring guidelines. The use of advanced data-mining strategy, such as template matching filters, auto-similarity search and deep-learning approaches is recently further fostering such a monitoring enhancing the seismic catalogues and lowering the magnitude of completeness of these areas. In this framework, we carried out an experiment where a small-aperture seismic array was installed around the gas reservoir of Collalto, in North Italy. The continuous velocimetric data, acquired for 25 days, were analysed through the application of the optimized auto-similarity search technique FAST. The array was conceived as a cost-effective network, aimed at integrating, right above the gas storage site, the permanent high-resolution Collalto Seismic Network. The analysis allowed to detect micro-events down to magnitude Ml=-0.4 within a distance of ~15km from the array. Our results confirmed that the system based on the array installation and the FAST data-analysis might contribute to lower the magnitude of completeness around the site of about 0.7.

1) Background: We tested whether AHR activation induces DNA damage, whether polymorphisms in genes related to risk of Non-Hodgkin lymphoma are associated with DNA damage, and whether the two conditions do interact with each other. 2) Methods: Our study population included 36 subjects, randomly selected among the population controls participating in a case-control study on lymphoma in Sardinia, Italy, who donated a blood sample. We investigated 47 single nucleotide polymorphisms (SNPs) previously reported to convey risk of lymphoma; the Dual-Glo® Luciferase Assay System to detect activation of the aryl hydrocarbon receptor (AhR) by the serum of study subjects; and the COMET Assay to detect DNA damage. 3) Results: Activation of the aryl hydrocarbon receptor did not increase DNA damage in our study population. On the other hand, the mutant allele (G) of rs1056932/BCL6 increased the occurrence of DNA damage (p = 0.045); such association was confirmed among AhR negative, but not AhR positive subjects. 4) Conclusions: We observed excess DNA damage associated with a gene polymorphism, namely rs1056932/ BCL6, previously reported in association with risk of lymphoma. No increase in DNA damage was associated with AhR activation per se, nor with the other gene polymorphisms we investigated.

The term neuroinflammation defines the reactions of astrocytes and microglia to alterations in homeostasis in the diseased central nervous system (CNS), the exacerbation of which contributes to the neurodegenerative effects of Alzheimer's disease (AD). Local environmental conditions, such as the presence of proinflammatory molecules, mechanical properties of the extracellular matrix (ECM) and local cell-cell interactions, are determinants of glial cell phenotypes. In AD, the load of the cytotoxic/proinflammatory amyloid β peptide (Aβ) is a microenvironmental component increasingly growing in the CNS, imposing time-evolving challenges on resident cells. This study aimed at investigating the temporal and spatial variations of the effects produced by this process on astrocytes and microglia, either directly or by interfering in their interactions. Ex vivo confocal analyses of hippocampal sections from the mouse model TgCRND8 at different ages have shown that overproduction of Aβ peptide induced early and time persistent disassembly of functional astroglia syncytium and promoted a senile phenotype of reactive microglia, hindering Aβ clearance. In the late stages of disease, these patterns were altered in the presence of Aβ-plaques, surrounded by typically reactive astrocytes and microglia. Morphofunctional characterization of peri-plaque gliosis revealed a direct contribution of astrocytes in plaque buildup that might result in shielding Aβ-peptide cytotoxicity and, as a side effect, in exacerbating neuroinflammation.

The antibody Trastuzumab (Tz) targeting ERBB2 has improved the prognosis of patients with breast cancer (BCa) that overexpress this receptor. Resistance to Tz negatively impacts prognosis. Several mechanisms have been reported to cause Tz resistance. The objective of this study was to identify common mechanisms in in vitro models of acquired BCa Tz resistance. In particular, we used three widely available ERBB2+ BCa cell lines adapted to grow in Tz. We performed several analyses to address possible changes in phenotype, proliferation, and ERBB2 membrane expres-sion common to the three Tz-R cell lines compared to wt, but none was found. High-resolution mass spectrometry analysis identified, instead, a common set of differentially expressed proteins (DEPs) in Tz-R vs. wt cells. Furthermore, bioinformatic tools revealed that all three Tz-R cell models shared a modulation of proteins involved in the metabolism of lipids, organophosphate biosynthetic process, and macromolecule methylation. Ultrastructural analysis confirmed altera-tion of lipid droplets in resistant cells. Our data strongly support the hypothesis that complex metabolic adaptation, including lipid metabolism, protein phosphorylation, and possibly chro-matin remodeling, may fuel Tz resistance. The identification of a common set of 10 DEPs in all three TZ-resistant cell lines may provide novel targets for therapeutic intervention.

Nonsense mutations cause several genetic diseases such as Cystic fibrosis, Duchenne muscular dystrophy, β-thalassemia, and Shwachman-Diamond syndrome. These mutations induce the formation of a premature termination codon (PTC) inside the mRNA sequence that leads to the aberrant translation, resulting in the synthesis of truncated polypeptides. Nonsense suppression therapy mediated by translational readthrough-inducing drugs (TRIDs) is a promising approach to correct these genetic defects. TRIDs generate a ribosome miscoding of the PTC named “translational readthrough” and restore the synthesis of full-length and potentially functional protein. The new oxadiazole-core TRIDs NV848, NV914, and NV930 showed translational readthrough activity in nonsense-related in vitro systems. In this work, the possible off-target effect of NV molecules on natural termination codons (NTCs) was investigated. Two different in vitro approaches were used to assess if the NV molecules treatment induce NTCs readthrough: 1) A study of translational induced p53 molecular weight and functionality; 2) the evaluation of two housekeeping proteins (Cys-C and β2M) molecular weights. Our results showed that the treatment with NV848, NV914, or NV930 do not induce any translation alterations in both experimental systems. Data suggested that NV molecules have a specific action for the PTCs and an undetectable effect on the NTCs.

Cancers overexpressing the ERBB2 oncogene are aggressive and associated with a poor prognosis. Trastuzumab is a ERBB2 specific recombinant antibody employed for the treatment of these diseases since it blocks ERBB2 signaling causing growth arrest and survival inhibition. While the effects of Trastuzumab on ERBB2 cancer cells are well known, those on the extracellular vesicles released from these cells are scarce. This study focused on ERBB2+ breast cancer cells and aimed to establish what type of EVs they release and whether Trastuzumab affects their morphology and molecular composition. To these aims, we performed immunoelectron microscopy, immunoblot, and high-resolution mass spectrometry analyses on EVs purified by differential centrifugation of culture supernatant. Here we show that EVs released from ERBB2+ breast cancer cells are polymorphic in size and appearance, and that ERBB2 is preferentially associated with large (120 nm) EVs. Moreover, we report that Tz induces the expression of a specific glycosylated 50 kDa isoform of the CD63 tetraspanin and modulates the expression of 51 EVs proteins, including TOP1. As these proteins are functionally associated with organelle organization, cytokinesis, and response to lipids, we suggest that Tz may influence these cellular processes in target cells at distant sites via modified EVs.

School bullying represents a widespread expression of violence in the peer context. Guided by the social-ecological model, this study investigated the longitudinal and transactional pathways linking domestic and neighborhood/community violence exposure (through direct victimization and witnessing), self-serving cognitive distortions (CDS), and school bullying perpetration. Furthermore, the cognitive desensitization hypothesis that the literature has supposed to develop in response to chronically violent contexts was examined. Two four‐wave cross-lagged panel mediation models were tested in a sample of 778 high school students (28.1% males; Mage [Time 1; T1] = 14.20, SD = 0.58). The results showed that both domestic and neighborhood/community violence exposure, as a victim and as a witness, respectively, were associated to self-serving CDs and bullying perpetration over time. Moreover, significant associations between CDs and bullying perpetration over time were found, with bidirectional effects for each of these longitudinal patterns. Finally, self-serving CDs were found to significantly mediate the relationships between both domestic violence victimization and community violence witnessing and school bullying perpetration. These findings highlight the need to consider school bullying as a social phenomenon stemming from a complex and bidirectional interplay between the individuals and the environments they inhabit confirming a basic postulate that “violence breeds violence”.

An outbreak of winter disease, complicated by severe respiratory syndrome, occurred in January 2020 in a high production dairy cow herd located in a hilly area of the Calabria region. Of the 52 animals belonging to the farm, 5 (9.6%) died with severe respiratory distress, death occurring 3-4 days after the appearance of the respiratory signs (caught and gasping breath). Microbiological analysis revealed absence of pathogenic bacteria whilst Real-time PCR identified the presence of RNA from Bovine Coronavirus (BCoV) in several organs: lungs, small intestine (jejunum), mediastinal lymph nodes, liver and placenta. Since being the only pathogen identified, BCoV was hypothesized to be the cause of the lethal pulmonary infection. Like the other CoVs, BCoV is able to cause different syndromes. Its role in calfhood diarrhoea and in mild respiratory disease is well known: we report instead the involvement of this virus in a severe and fatal respiratory disorder, with symptoms and disease evolution resembling that of Severe Acute Respiratory Syndromes (SARS).

Atopic dermatitis (AD) is a chronic inflammatory disorder presenting a dysregulated immune response and derangement of the epidermal barrier lipids. The Th2-type cytokines interleukin IL-4 and IL-13 play a prominent role in AD by activating the Janus Kinase/Signal Transduction and Activator of Transcription (JAK/STAT) intracellular signal axis. This study aimed to investigate the role of JAK/STAT in the lipid perturbations induced by Th2 signaling in 3D-epidermal equivalents. We used tofacitinib, a low-molecular-mass JAK inhibitor, to screen for the JAK/STAT-mediated deregulation of lipid metabolism. Th2 cytokines decreased the expression of elongases 1, 3, and 4, and serine-palmitoyl-transferase and increased that of sphingolipid delta(4)-desaturase, and carbonic anhydrase 2. Th2 cytokines inhibited the synthesis of palmitate and caused a depletion of triglycerides. This depletion was associated with altered PC profiles and fatty acid (FA) metabolism. Overall, the ceramide profiles were minimally affected. Except for most sphingolipids and very long chain FAs, the effects of Th2 on lipid pathways were reversed by co-treatment with tofacitinib. An increase in the mRNA levels of CPT1A and ACAT1, reduced by tofacitinib, suggests that Th2 cytokines promote FA beta-oxidation. In conclusion, pharmacological inhibition of JAK/STAT activation prevents the lipid disruption caused by halted homeostasis of FA metabolism.

Norovirus (NoV) is recognised as a major cause of epidemic and sporadic acute gastroenteritis (AGE) in all age groups. Information on the genetic diversity of the NoVs circulating in the 1980s and 1990s, before the development and adoption of dedicated molecular assays, is limited compared to the last decades. In the period 1986-2020, uninterrupted viral surveillance was conducted in symptomatic children hospitalized for AGE in Palermo, Italy, providing a unique time capsule for exploring the epidemiological and evolutionary dynamics of enteric viruses. In this 35-year long time span NoVs of genogroup II (GII) were detected in 15.6% of AGE requiring hospitalization, whilst GI NoVs in 1.4%. Overall, the predominant NoV capsid (Cap) genotype was GII.4 (60.8%), with temporal replacement of the GII.4 Cap variants and associated polymerase (Pol) types. The chronology of emergence and circulation of the different GII.4 variants were consistent with the data available in literature. Also, for GII.3 and GII.2 NoVs the circulation of different lineages/strains, differing in either the Cap or Pol genes or in both, was observed. This long-term study revealed the ability of NoVs to modify continuously and rapidly their genomic makeup and highlights the importance of surveillance activities for vaccine design.

COVID-19 breakout in Italy has caused a huge number of severely ill patients with a serious increase in mortality. Although lungs seem to be the main target of the infection very few information are available about liver involvement in COVID-19 infection, that could possibly evocate a systemic disease targeting a lot of organs. Since now there are no reports of large series of histological evaluation of liver morphology in this setting. Knowledge of histological liver findings connected to clinical data is crucial in management of this disease.Post-mortem wedge liver biopsies from 48 patients died for COVID-19 infection were available from two main hospitals located in northern Italy, Lombardy; all sample were obtained during autopsies. No patient has a significant clinical complain of liver disease or signs of liver failure before and during hospitalization; for each of them laboratory data focused on liver were available. All liver samples showed minimal inflammation features; on the other side, many histological pictures compatible with vascular alterations were observed, characterized by portal vein braches number increase associated with lumen massive dilatation, partial or complete recent luminal thrombosis of portal and sinusoidal vessels, fibrosis of portal tract, focally severely enlarged and fibrotic. Our preliminary results concerning histological liver involvement in COVID-19 infection confirm the clinical impression that liver failure is not a main concern and this organ is not the target of significant inflammatory damage; histopatological findings are highly suggestive for marked alteration of intrahepatic blood vessel network secondary to systemic alterations induced by virus that could target, besides lung parenchyma, cardiovascular system, coagulation cascade or endothelial layer of blood vessels.

Mesenchymal stromal cells (MSCs) are a subset of heterogeneous non-hematopoietic fibro-blast-like cells which play important roles in tissue repair, inflammation, and immune modula-tion. MSCs residing in the bone marrow microenvironment (BMME) functionally interact with hematopoietic stem progenitor cells regulating hematopoiesis. However, MSCs have also emerged in the last years as key regulator of tumor microenvironment. Indeed, they are now con-sidered as active players in the pathophysiology of hematologic malignancies rather than passive by-standers in hematopoietic microenvironment. Once the malignant event occurs, the BMME acquires cellular, molecular, and epigenetic abnormalities affecting tumor growth and progres-sion. In this context, MSC behavior is affected by signals coming from cancer cells. Furthermore, it has been showed that stromal cells themselves play a major role in several hematological malig-nancies’ pathogenesis. This bidirectional crosstalk creates a functional tumor niche unit wherein tumor cells acquire a selective advantage over their normal counterpart and are protected from drug treatment. It is therefore of critical importance to unveil the underlying mechanisms which activate a protumor phenotype of MSCs for defining unmasked vulnerabilities of hematological cancer cells which could be pharmacologically exploited to disrupt the tumor/MSCs coupling. The present review will focus on the current knowledge about MSC dysfunction mechanisms in the BMME of hematological cancers, sustaining tumor growth, immune escape, and cancer pro-gression.

HAX1 is a multifunctional protein involved in the antagonism of apoptosis in cellular response to oxidative stress. In the present study we identified HAX1 as novel binding partner for Che-1/AATF, a pro-survival factor which plays a crucial role in fundamental processes, including response to multiple stresses and apoptosis. HAX1 and Che-1 proteins show extensive colocalization in mitochondria and we demonstrated that their association is strengthened after oxidative stress stimuli. Interestingly, in MCF-7 cells, resembling luminal estrogen receptor (ER) positive breast cancer, we found that Che-1 depletion correlates with decreased HAX1 mRNA and protein levels, and this event is not significantly affected by oxidative stress induction. Furthermore, we observed an enhancement of the previously reported interaction between HAX1 and estrogen receptor alpha (ERα) upon H2O2 treatment. These results indicate the two anti-apoptotic proteins HAX1 and Che-1 as coordinated players in cellular response to oxidative stress with a potential role in estrogen sensitive breast cancer cells.

Pediatric obesity management strategies suffer from a high rate of dropout and persistence of weight excess, despite the use of new tools, such as the automated mobile technology (MT). We aimed to compare the efficacy of two personalized MT protocols with/without monthly in-presence recalls in terms of better adherence to follow-up, and improved anthropometric and lifestyle parameters. MT contacts consisted in three not automated messages per week, inserted between three-monthly in-presence regular visits with (PediaFit 1.2) or without (PediaFit 1.1) monthly in-presence recalls. The sample included 103 children (mean age 10 years, range 6-14) recruited in the Pediatric Obesity Clinic between January 2017 and February 2019, randomized in Intervention group (IG) (n=24 PediaFit 1.1; n=30 PediaFit 1.2) and Control group (CG) (total n=49). Both IGs achieved significantly better results than the CGs for all considered parameters. Comparison of the two IGs at the 6th month showed that IG 1.2 had a statistically significant lower drop-out rate (10% vs. 62%), along with improved body mass index z-score, systolic blood pressure, sleep duration and physical activity. The study suggests that the hybrid association of messaging through personalized/not automated MT plus monthly in-presence recalls may be considered for a favorable outcome of pediatric obesity programs.

Food allergy (FA) affects approximately 6–8% of children worldwide causing a significant impact on the quality of life of children and their families. In the years, the possible role of weaning in the development of FA has been studied. According to recent studies, the role of weaning in its development is still controversial and influenced by several factors, such as the type of food, the age at food introduction and family history. In this narrative review, we aimed to collected the most recent evidence about weaning and its role in FA development, organizing the gathered data based on both the type of study and the food.

Cystic Fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the CFTR gene, coding for the CFTR chloride channel. About 10% of the CFTR gene mutations are "stop" mutations, which generate a Premature Termination Codon (PTC), thus synthesizing a truncated CFTR protein. A way to bypass PTC relies on ribosome readthrough, which is the ribosome’s capacity to skip a PTC, thus generating a full-length protein. “TRIDs” are molecules exerting ribosome readthrough; for some, the mechanism of action is still under debate. We investigate a possible mechanism of action (MOA) by which our recently synthesized TRIDs, namely NV848, NV914, and NV930, could exert their readthrough activity by in silico analysis and in vitro studies. Our results suggest a likely inhibition of FTSJ1, a tryptophan tRNA-specific 2’-O-methyltransferase.

Previous studies show that women with a history of high-grade CIN have a greater risk of subsequent high-grade anogenital intraepithelial neoplasia or cancer, and the risk is greater for vaginal cancer than for anal and vulvar cancers. It is hypothesized that the laparoscopic hysterectomy procedure may cause a higher incidence of VaIN in hysterectomized women. There are few studies addressing this issue and they show mixed results. This study aimed to investigate the incidence of high-grade or worse VaIN in the population of women undergoing hysterectomy for CIN3 or benign uterine disease, illustrate treatment options and follow-up. Methods: This retrospective study was conducted on 170 women who underwent laparoscopic hysterectomy for high-grade cervical intraepithelial neoplasia (CIN3) or benign gynecological disease. The follow-up strategy included performing a cotest and colposcopy with biopsy if necessary. The median time between primary treatment and diagnosis of high-grade VaIN was 18 months. Results: High grade or worse VaIN was found in 8 patients after hysterectomy (4.7%). All cases of high-grade VaIN occurred in women with persistent HPV infection. The most frequent genotype was 16. Women hysterectomized for CIN3 showed an 8-fold greater risk than women hysterectomized for benign disease of developing high-grade VaIN. The risk of VaIN is low in women hysterectomized for benign disease. The risk of developing VaIN is greater in women with viral persistence Conclusion. All these elements suggest that it is the history of HPV-related disease of the lower genital tract and viral persistence, rather than hysterectomy itself, that should be considered a risk factor for the development of high-grade VaIN. After hysterectomy, patients with a history of CIN should undergo annual screening with vaginal dome cytology and HPV testing.

The study investigated the application of Wastewater-Based Epidemiology (WBE) as a tool for monitoring SARS-CoV-2 prevalence in a city in Northern Italy from October 2021 to May 2023. Starting from a widely applied deterministic model, this study proposed a variation to take into account population characteristics and virus biodegradation in the sewer network. The model calculated virus loads and corresponding COVID-19 cases over time in different areas of the city and was validated with healthcare data while considering viral mutations, vaccinations, and testing variability. The correlation between the predicted and reported cases was high across the three waves that occurred in the considered period, demonstrating the model’s capacity to predict relevant fluctuations in the number of cases. Population characteristics did not substantially influence the predicted and reported infection rates. Conversely, biodegradation significantly reduced the virus load reaching the wastewater treatment plant, resulting in a 30% reduction in the total virus load produced in the study area. This approach can be applied for comparing virus load values across cities with varying population demographics and sewer network structures, enhancing the comparability of WBE data for effective surveillance and intervention strategies.

The deficiency of Survival Motor Neuron (SMN) protein causes Spinal Muscular Atrophy (SMA), a rare neuromuscular disease that affects different organs. SMN is a key player in RNA metabolism regulation. An intriguing aspect of SMN function is its relationship with plasma membrane-associated proteins. Here, we provide a first demonstration that SMN affects the ATP-binding cassette transporter A1, (ABCA1), a membrane protein critically involved in cholesterol homeostasis. In human fibroblasts, we showed that SMN associates to ABCA1 mRNA, and impacts its subcellular distribution. Consistent with the central role of ABCA1 in the efflux of free cholesterol from cells, we observed a cholesterol accumulation in SMN-depleted human fibroblasts. These results were also confirmed in a SMA type I patient-derived fibroblasts. These findings not only validate the intimate connection between SMN and plasma mem-brane-associated proteins, but also highlight a contribution of dysregulated cholesterol efflux in SMA pathophysiology.

Some COVID-19 patients develop interstitial pneumonia that can evolve into Acute Respiratory Distress Syndrome (ARDS). This is accompanied by an inflammatory cytokine storm. SarS-CoV has proteins capable of promoting cytokine storm, especially in patients with comorbidities, including obesity. Since there is currently no resolutive therapy for ARDS and given the scientific literature regarding the use of adenosine, its application has been hypothesized. Adenosine through its receptors is able to inhibit the acute inflammatory process, increase the protection capacity of the epithelial barrier and reduce the damage due to an overactivation of the immune system, such as in cytokine storms. These features are known in ischemia / reperfusion models and could also be exploited in acute lung injury, with hypoxia. In light of these hypotheses, for compassionate use, a COVID-19 patient, with unresponsive respiratory failure, was treated with adenosine. The results showed a rapid and clear improvement in clinical conditions, with the negative effect of detection of SarS-CoV2.

K+ channels do play a role in cell shape changes observed during cell proliferation and apoptosis. Research suggested that the dynamics of aggregation of Aquaporin-4 (AQP4) into AQP4-OAPs isoforms can trigger cell shape changes in malignant glioma cells. Here, we investigated the relationship between AQP4 and some K+ channels in the malignant glioma U87 line. The U87 cells transfected with the human M1-AQP4 and M23-AQP4 isoforms were investigated for morphology, gene expression of KCNJ8, KCNJ11, ABCC8, ABCC9, KCNMA1, and Cyclin genes by RT-PCR, recording the whole-cell K+ ions currents by patch-clamp experiments. AQP4 aggregation into OAPs increases the plasma membrane functional expression of the Kir6.2 and SUR2 subunits of the KATP channels, and of the KCNMA1 of the BK channels in U87 cells leading to a large increase in inward and outward K+ ion currents. These changes were associated with changes in morphology with a decrease in cell volume in the U87 cells and an increase in the ER density. These U87 cells accumulate in the mitotic and G2 cell cycle. The KATP channel blocker zoledronic acid reduced cell proliferation in either M23 AQP4-OAPs and M1 AQP4-tetramers transfected cells leading to early and late apoptosis, respectively. BK channel sustains the efflux of K+ ions associated with the M23 AQP4-OAPs expression in the U87 cells, but it is downregulated in the M1 AQP4-tetramers cells; KATP channels are effective in the M1 AQP4-tetramers and M23 AQP4-OAPs cells. Zoledronic acid can be effective in targeting pathogenic M1 AQP4-tetramers cell phenotype inhibiting KATP channels and inducing early apoptosis.

We present our preliminary experience with transarterial radioembolization (TARE) with Yt-trium-90, and investigate the influence of additional treatments, injected activity, mean dose to the tumor on overall survival (OS). Our database was interrogated to retrieve patients who had undergone TARE with Yttrium-90 (90Y) glass or resin microspheres. The following information were searched: 1) type of pathology; 2) sex; 3) age; 4) administered activity; 5) mean dose to the tumor; 6) additional treatments; 7) OS. The OS of the different groups of patients were compared (p<0.05). A bivariate correlation (p<0.05) was used to investigate the association between injected activity and OS, and between mean dose to the tumor on OS. Thirty-nine patients were retrieved (Sex: 27 M, 12 F; mean age: 61.26 ± 14.95 years): 23 with hepatocellular carcinoma (HCC) and 16 with colorectal cancer (CRC) liver metastasis. Globally, patients with HCC demonstrated a sig-nificantly longer OS than those with CRC liver metastasis (22.66±19.11 vs. 10.41±8.75 months; p=0.022). Among patients with CRC liver metastasis, those receiving TARE and additional treatment demonstrated a longer OS than patients receiving only TARE (23.50±19.76 months vs. 8.54±5.31; p=0.018), there was a direct correlation between injected activity and OS (R=0.55, p=0.034) and between mean activity reaching the tumor and OS (R=0.812; p=0.008). Patients with HCC receiving TARE achieved a longer OS than those with CRC liver metastasis. Additional treatments, increasing injected activity and higher mean dose to the tumor seem beneficial for outcome, especially in patients with CRC liver metastases.

Diffuse intrinsic pontine glioma (DIPG), affecting children aged 4-7 years, is a rare, aggressive tumor that originates in the pons and then spreads to nearby tissue. DIPG is the leading cause of death for pediatric brain tumors due to its infiltrative nature and inoperability. Radiotherapy has only a palliative effect in stabilizing symptoms. In silico and preclinical studies identified ONC201, as a cytotoxic agent against some human cancer cell lines, including DIPG ones. Single crystal X-ray analysis of the complex of the human mitochondrial caseinolytic serine protease type C (hClpP) and ONC201 (PDB ID: 6DL7) allowed to identify hClpP as its main target. Hyperactivation of hClpP causes damage to mitochondrial oxidative phosphorylation and cell death. In some DIPG patients, receiving ONC201, an acquired resistance was observed. In this context, a wide program was initiated to discover original scaffolds for new hClpP activators to treat ONC201-non-responding patients. Harmaline, a small molecule belonging to the chemical class of β -carboline, was identified through Fingerprints for Ligands and Proteins (FLAP), a structure-based Virtual Screening approach. Molecular dynamics simulations and a deep in vitro investigation showed interesting information on the interaction and activation of hClpP by harmaline.

We investigated by Real-time PCR and end point PCR the presence of 10 potential zoonotic viruses in 91 small mammals sold as pets in pet shops of Southern Italy. The animals were analysed for: aichivirus, sapovirus, astrovirus, hepatitis A virus, noroviruses (GI and GII), rotavirus, circovirus, coronaviruses. Among the 9 species of small mammals analysed (golden hamsters, Java squirrels, mongolian gerbils, peruvian guinea pigs, pet mice, pet rats, dwarf rabbits, african hedgehogs and sugar gliders) 12 pet rats, 11 pet mice and 1 golden hamster tested positive to a PCR amplifying a conserved gene (RdRp) of coronavirus. However further characterizaton by sequencing gave not conclusive results. A pet rat resulted instead positive to aichivirus and its sequence showed similarity with a murine kobuvirus-1 strain identified in China. To our knowledge, this is the first study reporting the detection of aichivirus in rodents in Italy, the virus probably introduced through the importation of animals from Asia. Since living in close contact to humans, expecially with children, the continuous monitoring of the small mammals is very important to avoid the spread of new pathologies among animals and humans and further investigation is desirable in order to safeguard public health.

Background: Malnutrition is a frequent condition in the elderly and is associated with prolonged hospitalization and increased mortality. However, the impact of malnutrition among elderly patients with acute myocardial infarction has not been clarified yet. Methods and Results: We have enrolled 174 patients aged 65 years and over, admitted with the diagnosis of acute myocardial infarction (AMI) who underwent to the evaluation of nutritional status by Mini Nutritional Assessment (MNA) and of mortality risk by Grace score 2.0. All-cause mortality was the outcome considered for this study. Over a mean follow-up of 24.5 ± 18.2 months, 43 deaths have been registered (24.3%). Non-survivors were more likely to be older, with worse GFR, lower SBP, lower albumin and MNA score, higher prevalence of Killip classification III-IV grade, and higher Troponin I levels. Multivariate Cox proportional analysis revealed that Grace score and MNA showed a significant and independent impact on mortality, (HR = 1.76, 95% CI = 1.34–2.32 and HR = 0.56, 95% CI = 0.42–0.73, respectively). Moreover, the clinical decision curve revealed a higher clinical net benefit when the MNA was included compared to the partial models without MNA. Conclusions: Nutritional status is an independent predictor of long-term mortality among elderly patients with AMI. MNA score in elderly patients with AMI may help prognostic stratification and identification of patients with/at risk of malnutrition in order to apply interventions to improve nutritional status and maybe survival in this population.

Brain aging in mammals is characterized by morphological and functional changes of neural cells. Macroscopically, this process leading to progressive cerebral volume loss and functional decline, includes memory and motor neuron defiance and behavioral disorders as well. Morphologically, brain aging is associated with aged neurons and astrocytes, appearing enlarged and flattened, and expressing an enhanced pH-dependent β-galactosidase activity. Multiple mechanisms are considered hallmarks of cellular senescence in vitro. Among them, cell cycle arrest, increased lysosomal activity, telo-mere shortening, oxidative stress and DNA damage. The most common markers for senescence identification were identified in: i) proteins implicated in cell cycle arrest, such as p16, p21, p53 ii) increased lysosomal mass iii) increased reactive oxygen species (ROS) and senescence associated secretory phenotype (SASP) expression. Finally, dys-functional autophagy, a process occurring during aging, contributes to alter brain homeostasis. The aim of this review is to summarize and update the most recent knowledge about brain aging with a comparative approach, where similarities and differences in some mammalian species are considered.

Brain vascular health appears to be of critical importance for protection against the development of amyotrophic lateral sclerosis (ALS) as well as the slowing of disease progression. ALS patients often demonstrate cardiovascular risk factors and commonly suffer from cerebrovascular disease, with evidence of pathological alterations in the small cerebral vessels. Impaired vascular brain health has detrimental effects on motor neurons as lowered vascular endothelial growth factor levels compromise endothelial cell formation, promoting blood-brain barrier leakage and inflammation. Increased turnover of neurovascular unit cells precedes their senescence, which, together with pericyte alterations, further fosters the failure of toxic metabolite removal. We here provide a comprehensive overview of the pathogenesis of impaired brain vascular health in ALS and how novel magnetic resonance imaging techniques can aid its detection. In particular, we discuss vascular patterns of blood supply to the motor cortex with the number of branches from the anterior and middle cerebral arteries acting as a novel marker of resistance and resilience against downstream effects of vascular risk and events in ALS. We outline how certain interventions adapted to patient needs and capabilities have the potential to mechanistically target the brain microvasculature towards favorable motor cortex blood supply patterns. Through this strategy, we aim to guide novel approaches to ALS management and a better understanding of ALS pathophysiology.

Neuroblastoma (NB) is a solid tumor occurring in infancy and childhood, whose high-risk form has currently a survival rate &lt; 50 %, despite aggressive treatments. Additionally, drugs-induced secondary tumorigenesis and the emergency of drug resistance worsen the already worrying scenario, calling for an urgent development of new extra-genomic treatments. Quaternary phosphonium salts (QPSs) possess both antimicrobial and anticancer effects. Triphenyl phosphonium salts (TPPs) are mitochondria-targeting compounds, exerting anticancer effects, impairing mitochondria functions and damaging DNA, at the same time. TPP-based bola-amphiphiles, previously proven to self-assemble nanoparticles (NPs) in water and successfully assayed as possible antibacterials, were never tested as suitable antitumor agents. Here, aiming at the development of new antitumor devices to counteract resistant forms of NB, the anticancer effects of a TPP-based amphiphile molecule have been investigated for the first time. To this end, we considered the water-soluble sterically hindered quaternary phosphonium salt (BPPB) encompassing two triphenyl phosphonium groups linked by a C12 alkyl chain, thus embodying both the characteristics of mitochondria-targeting compounds and those of bola-amphiphiles. The anticancer effects of BPPB were assessed against HTLA-230 human stage-IV NB cells and their counterpart resistant to etoposide (ETO), doxorubicin (DOX) and to many other therapeutics (HTLA-ER). Determined IC50 values were very low on both cell populations, already after 24 hours of treatment, when cells viability did not significantly differ from that observed for the longest exposure timing. Moreover, to investigate a putative future inclusion of BPPB in a chemotherapeutic cocktail for NB, its cytotoxic effects were assessed against mammalian cell lines. These included monkey kidney cells (Cos-7), human hepatic cells (HepG2), a lung-derived fibroblast cell line (MRC-5) and red blood cells. From appreciable to very high selectivity indices have been determined after 24 hours treatments, an exposure time after which both NB cell populations tested appeared already fully exterminated.

Objectives: Monoclonal antibodies (mAbs) have proven to be a valuable tool against COVID-19, mostly among subjects with risk factors for progression to severe illness. Tixagevimab/cilgavimab (TIX/CIL), a combination of two Fc-modified human monoclonal antibodies, has been recently approved to be employed as early treatment. Methods: Two groups of immunocompromised patients exposed to different early treatments (i.e., TIX/CIL vs. other mAbs [casirivimab/imdevimab, bamlanivimab/etesevimab, sotrovimab]) were compared in terms of clinical outcomes (hospitalization and mortality within 14 days from administration) and time to the negativity of nasal swabs. We used either Pearson’s chi-square or Fisher’s exact test for categorical variables, whereas the Wilcoxon rank–sum test was employed for continuous ones. Kaplan–Meier curves were produced to compare the time to nasopharyngeal swab negativity. Results: Early treatment with TIX/CIL was administered to 19 immunocompromised patients, while 89 patients received other mAbs. Most of them were solid organ transplant recipients or suffering from hematologic or solid malignancies. Overall, no significant difference was observed between the two groups in terms of clinical outcomes. In the TIX/CIL group, one patient (1/19, 5.3%), who was admitted to the emergency room within the first 14 days from treatment and was hospitalised due to COVID-19 progression, died. Regarding the time to nasal swab negativity, no significant difference (p=0.088) emerged. Conclusions: Early treatment of SARS-CoV-2 infection with TIX/CIL shows favourable outcomes in a small group of immunocompromised patients, reporting no significant difference when compared to similar patients treated with other mAbs.

Extrauterine growth restriction (EUGR) is a common complication and a known risk factor for impaired development in very low birth weight (VLBW) preterms. We report a population of 288 patients with no or with low grade MRI lesions scanned at term equivalent age (TEA) born between 2012 and 2018. Griffiths mental development scale II (GMDS II) at 2 and 3 years, preterm complications and weight growth were retrospectively analysed. EUGR was defined for weigth z-score ˂10th percentile at TEA, 6 and 12 months of correct age or as z-score decreased by 1-point SDS from birth to TEA and from TEA to 6 months. Multivariate analysis showed that a higher weight z-score at 6 months is protective for global developmental quotient (DQ) at 2 years (OR 0.74; CI 95% 0.59-0.93; p=0,01). EUGR at 6 months was associated with worse locomotor, personal-social, language and performance DQ at 2 years and worse language and practical reasoning DQ at 3 years. In conclusion a worse weight z-score at 6 months of age seems to be an independent risk factor for significantly reduced GMDS in many areas. These results suggest to better invest on post-discharge nutritional, optimizing family nutritional education.

Although the anti-COVID-19 vaccination has proved to be an effective preventive tool, "break-through infections" have been documented in patients with complete primary vaccination course. Most of the SARS-CoV-2 neutralizing antibodies pro-duced after SARS-CoV-2 infection target the spike protein receptor-binding domain which has an important role in facilitating viral entry and infection of the host cells. SARS-CoV-2 has demonstrated the ability to evolve by accumulating mutations in the spike protein to escape the humoral response of the host. The aim of this study is to compare the titers of neutralizing an-tibodies against the variants of SARS-CoV-2 by analyzing the sera of recovered and vaccinated healthcare workers (HCWs). 293 HCWs were enrolled and divided into three cohorts as follows: 91 recovered from SARS-CoV-2 infection (nVP); 102 vac-cinated who became positive after the primary cycle (VP); 100 vaccinated with complete primary cycle who concluded the follow-up pe-riod without becoming positive (VN). Higher neutraliza-tion titers were observed in the vaccinated subjects’ arms com-pared to the nVP arm. Differences in neutralization titers between arms for single variant were statistically significant (p<0.001) except for titers against the Alpha variant (p<0.05) between nVP and VP. Within the nVP group, the number of subjects with the absence of neutralizing antibodies was high. The presence of high-er titers in patients with a complete primary cycle compared to patients recovered from the infec-tion suggests a better efficacy of artificial immunization compared to natural im-munization, further encouraging the promotion of vaccination even in subjects with previous infection.

Patients with pT1 high-grade (HG) bladder cancer (BC) and a very high risk of progression might benefit from immediate radical cystectomy (RC), but this option remains controversial. Validation of a standardized method to evaluate the extent of lamina propria (LP) invasion (with recognized prognostic value) in transurethral resections (TURBT) specimens is still needed. The Rete Oncologica Lombarda (ROL) system showed a high predictive value for progression after TURBT in recent retrospective studies. Our aim was to validate ROL system on a large mono-institutional prospective series of primary urothelial carcinomas. From 2016 to 2020, we adopted ROL for all patients with pT1 HG BC on TURBT. We employed a 1.0-mm threshold to stratify tumors in ROL1 and ROL2. A total of 222 pT1HGBC were analyzed. Median age was 74 years, with male predominance (73.8%). ROL was feasible in all cases: 91 cases were ROL1 (41%) and 131 ROL2 (59%). At a median follow up of 26.9 months (IQR 13.8-40.6), we registered 80 recurrences and 40 progressions. ROL was a significant predictor of tumor progression at both univariable (HR 3.53; CI 95% 1.56 – 7.99; p&lt;0.01) and multivariable (HR 2.90; CI 95% 1.25 – 6.75; p=0.01) Cox regression analyses. At Kaplan-Meier estimates, ROL showed correlation with both PFS (p=0.0012) and RFS (p=0.0167). Our results confirmed the strong predictive value of ROL for progression on a large prospective series. We encourage the application of ROL for reporting the extent of LP invasion, substaging T1 HG BC, and improving risk tables for urological decision making.

Headaches are among the most prevalent and disabling disorders and there are several patients’ unmet needs in current pharmacological options, while a growing interest is focusing on nutritional approaches as non-pharmacological treatments. Among these, the most promising seems to be the ketogenic diet (KD). Exactly 100 years ago, KD was used to treat pediatric forms of drug-resistant epilepsy, but progressively applications of this diet also involved adults and other neurological disorders. Evidence of KD effectiveness in migraine comes from 1928, but in the last years different groups of research and clinicians paid attention to this therapeutic option to treat patients with drug resistant migraine and cluster headache, and/or comorbid with metabolic syndrome. Here we describe all the existing evidence on the potential benefits of KDs in headaches, explore in deep all the potential mechanisms of action involved in the efficacy, and synthesize results of working meetings of an Italian panel of experts on this topic. Aim of the working group is the creation of a consensus on indications and clinical practice to treat with KDs patients with headache. The results here we present are the base for further improvement in the knowledge and application of KDs in the treatment of headaches.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

Background. Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy worldwide. Brain metastasis (BM) is quite an uncommon presentation. However, the likelihood of central nervous system (CNS) metastasization should be considered in the context of disseminated disease. The therapeutic management of BMs is an unmet clinical need, to date. Case presentation. We identified across different Cancer Centers six cases of both BRCA wild-type and BRCA-mutated EOC spreading to the CNS. They presented either with a single brain lesion or with multiple lesions and most of them had intracranial-only disease. All cases received Poly-ADP ribose polymerase inhibitor (PARPi) maintenance, as by clinical practice, for a long time within a multimodal treatment approach. We also provide an insight into the available body of work regarding the management of this intriguing disease setting, with a glimpse of future therapeutic challenges. Conclusion. Despite the lack of unanimous guidelines, multimodal care pathways should be encouraged for optimal disease control of this unfortunate patient’s subset. Albeit not being directly investigated in BM patients, the PARPi maintenance is deemed to have a valuable role in this setting. Prospective research, aimed to implement worthwhile strategies in the multimodal patient journey of BMs from EOC, is eagerly awaited.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.

The impact of interaction SS with MJO on rainfall along Java Island to East Nusa Tenggara has been studied using daily rainfall observation data from 2140 weather observation stations, which are also equipped with GSMaP, OLR, and ERA5 data. There were 61 SS events found, 17 during active MJO and 44 in inactive MJO. Rainfall increases more in the western study area when the active MJO and more in the eastern study area when the inactive MJO is due to SS. SS reduces rainfall in the Jakarta region, regardless of the activity or inactivity of the MJO. SS causes extreme rainfall to only occur in a small part of certain areas, so it tends to significantly reduce the possibility of extreme rainfall. In the southern part of the IMC, SS predominates over MJO in supporting increased water vapor transport. Large-scale synoptic circulations like the monsoon, SS, and MJO can interact with local land-sea wind circulation to produce spatiotemporal variability in rainfall on Java Island. Rainfall mostly increases in the afternoon and decreases in the morning when SS occurs, whether there is MJO or not. Convective instability analysis indicates that SS increases precipitation, most likely by lowering CIN and raising VIMFC.

The Simultaneous Localization And Mapping (SLAM) scanner is an easy and portable Light Detection And Ranging (LiDAR) data acquisition device. Its main output is a 3D point cloud covering the scanned scene. Regarding the importance of accuracy in the survey domain, this paper aims to assess the accuracy of two SLAM scanners: the NavVis VLX and the BLK2GO Scanner. This assessment is conducted for both outdoor and indoor environments. In this context, two types of reference data are used: the Total Station (TS) and the static scanner Z+F Imager 5016. To carry out the assessment, four comparisons are tested: cloud to cloud, cloud to mesh, mesh to mesh, and edge detection board assessment. However, the results of the assessments confirm that the accuracy of indoor SLAM scanner measurements (5 mm) is greater than that of outdoor ones (between 10 mm and 60 mm). Moreover, the comparison of cloud to cloud provides the best accuracy regarding direct accuracy measurement without manipulations. Finally, based on the high accuracy, scanning speed, flexibility, and the accuracy differences between tested cases, it is confirmed that SLAM scanners are effective tools for data acquisition.

In recent years, electroencephalogram (EEG) emotion recognition has emerged as a research hotspot in the field of artificial intelligence (AI). Despite advancements in EEG-based emotion recognition, room for enhancing performance persists due to EEG signal redundancy and limitations in feature extraction, leading to inefficient models and emotional information loss. To fully utilize EEG's emotional information and improve recognition accuracy while reducing computational costs, this paper proposes a Convolutional-Recurrent Hybrid Network with a dual-stream adaptive approach and an attention mechanism (CSA-SA-CRTNN). Firstly, the model utilizes a CSAM module to assign corresponding weights to EEG channels. Then, an adaptive dual-stream convolutional-recurrent network (SA-CRNN and MHSA-CRNN) is applied to extract local spatial-temporal features. After that, the extracted local features are concatenated and fed into a temporal convolutional network with a multi-head self-attention mechanism (MHSA-TCN) to capture global information. Finally, the extracted EEG information is used for emotion classification. We conducted binary and ternary classification experiments on the DEAP dataset, achieving 99.26% and 99.15% accuracy for arousal and valence in binary classification, and 97.69% and 98.05% in ternary classification, surpassing relevant algorithms. Additionally, the model's efficiency is significantly higher than other models, achieving better accuracy with lower resource consumption.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Superior fiber quality is one of the most important objectives in cotton breeding. To detect the genetic basis underlying fiber quality, an F2 population containing 413 plants was constructed by crossing Jifeng 914 and Jifeng 173, both of which have superior fiber quality, with Jifeng 173 being better. Five fiber quality traits were investigated in the F2, F2:3, F2:4, and F2:5 populations. Quantitative trait loci (QTL) mapping was conducted based on a high-density genetic map containing 11,488 single nucleotide polymorphisms (SNPs) and spanning 4,202.12 cM in length. Transgressive segregation patterns and complex correlations in the five tested traits were observed. A total of 108 QTLs were found, including 27 for fiber length (FL), 16 for fiber strength (FS), 24 for micronaire (MC), 17 for fiber uniformity (FU), and 24 for fiber elongation rate (FE). Chromosome A7 contained 12 QTL, ranking the first. No QTL was found on chromosome D1 and D11. Each QTL contributed 1.98%–21.45% to the phenotypic variation (PV), including 13 major effect QTLs that contributed more than 10% toward PV. Two QTLs could be repeatedly detected in three populations, including qFL-D3-2 in F2, F2:4, and F2:5 with 9.18%–21.45% of PV, qFS-A11-1 in F2:3, F2:4 and F2:5 with 6.05%–10.41% of PV. Another seven stable QTLs could be detected in two populations, including four major effect QTLs: qFL-A12-3, qFS-D10-2, qMC-D6-2, and qMC-D8-1. Fourteen QTL-overlapping regions were found, which might explain the complex correlations among the five phenotypic traits. Four regions on chromosome A11, D3, D6, and D10 covered by both stable and major effect QTLs are promising for further fine mapping. The genomic regions of the two QTLs detected in three populations and the four major effect QTLs contain 810 genes. Gene functional analysis revealed that the annotated genes are mainly involved in protein binding and metabolic pathways. Fifteen candidate genes in the qFL-D3-2 region are highly expressed in fiber or ovules during fiber initiation, elongation, secondary cell wall thickening, or maturation stages. qRT-PCR revealed that Ghir_D03G005440.1 and Ghir_D03G011310.1 may play a role in promoting fiber initiation, Ghir_D03G006470.1 may be beneficial for promoting fiber elongation. This study provides more information for revealing the molecular genetic basis underlying cotton fiber quality.

Currently there are fewer depth models applied to pepper picking detection, while the existing generalized neural networks have problems such as large model parameters, long training time, and low model accuracy.In order to solve the above problems, this paper proposes a Yolo-chili target detection algorithm for chili pepper detection. First, the classical target detection algorithm yolov5 is used as a benchmark model, and an adaptive spatial feature pyramid structure combining the attention mechanism and the idea of multi-scale prediction is introduced to improve the model's detection effect on occluded peppers and small target peppers. Secondly, a three-channel attention mechanism module is introduced to improve the algorithm's long-distance recognition ability and reduce the interference of redundant testers. Finally, the quantized pruning method is used to reduce the model parameters and realize the lightweight processing of the model. Applying the method to the homemade chili pepper dataset, the AP value of chili pepper reaches 93.11%; the accuracy rate is 93.51% and the recall rate is 92.55%.The experimental results show that yolo-chili is able to achieve accurate and real-time pepper detection under complex orchards.

The temporary immersion system bioreactor named GreenTray®[2], [3]presents advantages over the existing ones. Firstly, there is no need to use forceps to move the shoots or plantlets in or out of the recipient, neither the use of scalpel to divide them. Secondly, the basis of the shoot can remain in the GreenTray® and can sprout again in several cycles of growth. These two characteristics reduce the costs in the process of micropropagation. Besides, shoots or plantlets development is enhanced by the aeration of the recipient, thus enriching with CO2 the recipient atmosphere. The chapter describes and provides images and values of interest in (1) the micropropagation process of some commercial Prunus or Pyrus rootstocks; (2) the plantlet growth under autotrophic conditions; and (2) the inoculation of plants with pathogens that reproduce in vitro the symptoms observed in vivo, using the GreenTray® bioreactor.

Aiming at the problems of inaccurate segmentation of long object and information loss of small object in real-time semantic segmentation algorithm, this paper proposes a lightweight multi-branch real-time semantic segmentation network based on BiseNetV2. The new auxiliary branch makes full use of spatial details and context information to cover the long object in the field of view. Meanwhile, in order to ensure the inference speed of the model, the asymmetric convolution is used in each stage of the auxiliary branch to design a structure with low computational complexity. In the multi-branch fusion stage, the alignment and fusion module is designed to provide guidance information for deep and shallow feature mapping, so as to make up for the problem of feature misalignment in the fusion of information at different scales, and thus reduce the loss of small target information. In order to further improve the model’s awareness of key information, a global context module is designed to capture the most important features in the input data. The proposed network uses NVIDIA GeForce RTX 3080 Laptop GPU experiment, on the road street view data set Cityscapes and CamVid average occurring simultaneously ratio reached 77.1% and 78.4% respectively, with running speed of 127 frames/s respectively and 112 frames/s. The experimental results show that the proposed algorithm can achieve real-time segmentation and improve the accuracy significantly, showing good semantic segmentation performance

Excess nitrogen in agricultural drainage poses a serious threat to the water quality safety of the Yellow River basin. Utilizing aquatic plants to modify the rhizosphere microbial community structure and facilitate nitrogen transformation is a crucial strategy for mitigating regional water eutrophication. Our results revealed that the denitrification rate (DR), dissimilatory nitrate reduction to ammonium rate (DNRAR) and nitrogen fixation rate (NFR) of rhizosphere sediments exhibited a significant increase in artificially cultivated ditch. Compared with those in natural ditches, the richness of the bacterial community and the relative abundances of Bacteroidota, Verrucomicrobiota, Firmicutes, Anaeromyxobacter and Geobacter, which are involved mainly in the nitrogen cycle, in the rhizosphere sediments of artificially cultivated ditch were significantly greater due to improvements in environmental conditions. In artificially cultivated ditch, the dominant functional genes affecting DRNARs in the rhizosphere sediments of P. australis were nrfC and nrfA, while DRs were driven mainly by norB and napA, which were influenced by the nitrogen and carbon levels; and the dominant functional genes affecting NFRs in the rhizosphere sediments of T. orientalis were nifD, nifK and nifH. Our results provide a scientific basis for the use of aquatic plants for mitigating excess nitrogen levels in agricultural drainage.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

In this paper we study a class of impulsive delayed neural networks with parameter uncertainties and reaction-diffusion terms. Using the properties of M-matrices and some inequality techniques, some sufficient conditions are derived to guarantee the global exponential stability of the given system. The results obtained are presented by simple algebraic inequalities, which are certainly more concise than previous methods. Finally, the validity and usefulness of our results are illustrated by arithmetic examples.

Pyrops candelaria is one of the common pests of fruit trees, but the research on the pathogenic microorganisms it may carry is very limited. Therefore, it is essential to reveal the pathogenic microbes it carries and their potential hazards. This study found a new virus from the transcriptome of P. candelaria, which was first reported in P. candelaria and named as PyCaV (Pyrops candelaria associated virus). RACE and bioinformatics assay revealed that the full-length of PyCaV is 10855 bp with the polyA tail, containing a single open reading frame (ORF) encoding a polyprotein consisting of 3171 amino acid (aa). The virus has a typical Iflavirus structure, including two rhv domains, a RNA helicase domain (HEL), a 3C cysteine protease domain (Pro), and a RNA-dependent RNA polymerase domain (RdRp). Further phylogenetic analysis revealed that this virus belongs to family Iflaviridae and sequence alignements analysis suggedted PyCaV is new member in unassigned genus of family Iflaviridae. Further in-depth analysis of virus-infection-part showed that PyCaV is distributing in the whole longan lanternfly, including its head, chest, and abdomen, but more PyCaV was identified in the chest. The distribution of PyCaV in different parts of P. candelaria was further explored, which showed that more PyCaV were detected in its piercing-sucking mouthparts and chest viscera. Statistical analysis showed that the PyCaV infection was affected by time and locations.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p &lt; 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

With the burgeoning growth of online retail, the issue of counterfeit products has become a significant threat to both consumer trust and brand integrity, posing challenges to sustainable market practices. Online retail platforms are promoted to redesign their channel structures and enhance brand traceability to tackle counterfeits using blockchain technology. To investigate the interactions between blockchain technology and the channel structures of online retail platforms, we design a game theory model incorporating a manufacturer with(out) blockchain participation selling products via an online retail platform that operates an agency channel and/or a reselling channel. We show that the critical trade-off of blockchain participation comprises the brand assurance effect of the blockchain, the channel competition intensification effect, and the blockchain adoption cost. The platform is capable of strategically designing the channel structure to encourage (while discouraging) blockchain participation by the manufacturer. Our analysis highlights the complementarity between blockchain participation and the channel structure. Furthermore, the effect of the consumer’s belief in the reselling channel, the commission fee in the agency channel, and the substitutability between channels are investigated in depth. The research provides valuable insights for online retail platforms and policymakers seeking to foster a sustainable and trustworthy e-commerce ecosystem.

In this paper, we extend the KdVSKR equations in (1+1)-dimension and (2+1)-dimension to fractional KdVSKR equations with modified Riemann-Liouville derivative. The (2+1)-dimensional KdVSKR equation, which is a recent extension of (1+1)-dimensional KdVSKR equation, can model the resonances of solitons in shallow water. By means of the Hirota bilinear method, finite symmetry group method and consistent Riccati expansion method, many new interaction solutions have been derived. Soliton-cnoidal interaction solution of the (1+1)-dimensional fractional KdVSKR equation has been derived for the first time. For the (2+1)-dimensional frac-tional KdVSKR equation, two-wave interaction solutions and three-wave interaction solutions, including dark-soliton-sine interaction solution, bright-soliton-elliptic interaction solution, and lump-hyperbolic-sine interaction solution, have been derived. Impact of the fractional order on the shapes of these solutions has been illustrated by figures. Three-wave interaction solutions of fractional systems have not been reported in the existing references. The research idea in this paper can be applied to other fractional differential equations.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.