Urban mobility and sustainable transportation are fundamental for the European Union's goal of achieving climate neutrality by 2050. The EU encourages national governments to prioritize zero-emission urban transport systems that emphasize safety, accessibility, and inclusiveness. Promoting walking plays a fundamental role in sustainable urban mobility, offering advantages such as emission reduction, better air quality, and enhanced public health. Recent research underscores the importance of creating appealing and safe pedestrian environments to encourage walking. These efforts align with the United Nations' Agenda 2030 sustainability goals, particularly Objective 11, which aims to build inclusive, safe, and sustainable cities and communities. This paper explores the factors influencing pedestrians' willingness to walk and categorizes them into four main groups: Physical Characteristics, Comfort, Safety, and Attractiveness. Significantly, the study reveals that the importance of these factors varies based on demographics, mainly the age of the users. Understanding these factors and their relative significance for pedestrian satisfaction is crucial for shaping effective policies and urban planning strategies aimed at promoting sustainable mobility. By prioritizing pedestrian satisfaction and addressing the specific needs and preferences of diverse groups, cities can create more walkable and environmentally friendly urban environments. These findings offer valuable insights for policymakers and urban planners working toward EU climate-neutral objectives and enhancing the well-being of citizens.

This research investigates the utilization of human driving models in autonomous vehicles, particularly in scenarios with minimal or no interactions with other vehicles. Human driving models provide valuable insights into driver behavior and play a crucial role in shaping the behavior of autonomous vehicles, enhancing their performance and user experience. The primary focus of the study is the creation of a planning model for autonomous vehicles when navigating roundabouts in the absence of traffic. This model seeks to emulate human driving behavior, ensuring predictability, safety, optimization of traffic flow, and adaptation to various roundabout geometries. To achieve this, the research introduces a trajectory model that takes into account geometric attributes and speed variations within roundabouts. The model is calibrated using empirical data and generalizes parameters through statistical regression methodologies. This model is referred to as "MRoundabout" and is evaluated for its consistency in generating plans that closely mimic human driving behavior within roundabouts. While the study presents a promising approach, it acknowledges limitations related to the model's reliance on geometric attributes and its inability to account for external factors like weather conditions. This research underscores the importance of bridging the gap between theoretical research and practical application, with the aim of enhancing safety and the overall user experience in real-world driving scenarios.

Background: The reference test for SARS-CoV-2 detection is the reverse transcriptase real time PCR (real time RT-PCR). However, evidences reported that real time RT-PCR has a lower sensitivity compared with the droplet digital PCR (ddPCR) leading to possible false negative in low viral load cases. Methods: We used ddPCR for viral genes N1 and N2 on 20 negative (no detection) samples from symptomatic hospitalized COVID-patients presenting fluctuating real time RT-PCR results and 10 suspected samples (Ct value>35) from asymptomatic not hospitalized subjects. Results: ddPCR performed on RNA revealed 65% of positivity for at least one viral target in the hospitalized patients group of samples (35% for N1 and N2, 10% only for N1 and 20% only for N2) and 50% in the suspected cases (30% for N1 and N2, while 20% only for N2). On hospitalized patients’ samples, we applied also a direct ddPCR approach on the swab material, achieving an overall positivity of 83%. Conclusion: ddPCR, in particular the direct quantitation on swabs, shows a sensitivity advantage for the SARS-CoV-2 identification and may be useful to reduce the false negative diagnosis, especially for low viral load suspected samples.

Background: the devastating outbreak of COVID-19 poses serious challenges for the diagnostics laboratories, which are often facing global shortage of reagents and equipment. With the aim of increasing the diagnostic throughput for SARS-CoV-2 molecular test, the purpose of this study was to validate an additional RNA extraction method respect to those already recommended by WHO and the US Centers for Disease Control and Prevention (CDC). Methods: a new protocol for RNA extraction from nasopharyngeal swab was set up, adapting the Qiagen RNeasy 96 plate and validated on a set of 100 clinical samples analyzed in parallel by Roche-Magnapure method (already recommended by CDC guidelines). Results: the internal control and target genes analysis showed a good agreement between the two extraction methods indicating that the two methods can be considered equivalent and that the RNeasy-adapted method can be applied for the SARS-CoV-2 diagnostics. The addition of this new extraction method resulted in a throughput increase for SARS-CoV-2 molecular test of about 2000 samples/month during the initial months of the pandemic emergency in which the lack of reagents for the extraction led to an insufficient sample processing throughput of the analysis of the swabs.

There is a growing interest in the endocannabinoid system and the gut microbiota. Both areas have been suggested to play a role in endometriosis, however this is yet to be studied comprehensively. The purpose of this narrative review is to identify the gaps in endometriosis research in the context of these two areas. It underscores the limited knowledge regarding the involvement of the endocannabinoid system and gut microbiota in endometriosis. Further research in these areas is essential to unlock the therapeutic potential of cannabis and enhance the understanding of endometriosis pathogenesis.

In the last decades, the impacts of urbanization on the hydrological cycle have led to an increase in the frequency and magnitude of urban flooding events, also amplified by the effects of climate change. Sustainable Drainage Systems (SuDS) provide a revolutionary change in this field, improving the sustainability and resilience of cities. This research explores the integration of different SuDS with the aim of significantly reducing both flow volume and celerity of floods in a residual urban catchment area of metropolitan city of Querétaro (Mèxico), where extreme rainfall frequently occurs. This catchment is a representative suburb of urban pressure and environmental degradation problems. Currently, managing storm water under climate uncertainty through a multi-disciplinary approach is a major concern in this urban area. A 1D-2D coupling model of shallow water equations, finite volume method, unstructured meshing method, and hybrid parallel computing application defined the optimal configuration of SuDS at catchment scale to reduce the flood vulnerability in Querétaro. Specifically, in this paper we explore the management issues of the proposed SuDS configuration that acts as a water resource system with multiple purposes. A generic simulation model called MODSIM was applied to simulate the designed urban drainage system under a balanced IPCC future climate scenario in terms of reliability, resilience and vulnerability against water scarcity.

As coastal and marine ecosystems, even the inland waters can be deeply affected by human-driven impacts. Consequently, the internal waters belonging to closed or semi-closed basins due to their hydrographic and morphological conditions can be subject to even more dramatic consequences in terms of conservation and overall ecosystem functioning maintaining. Despite the Albano Lake is listed among the Natura 2000 network sites (IT6030038), several elements of its landscape complexity have already experimented clearly visible alterations: from certain landscape features alterations to the loss of some iconic vegetal and animal species characterizing the lake environment in the past. Therefore, a virtuous commitment awaits us and we have the moral duty of acting in order to restore such degraded habitats. Each environmental restoration intervention and/or clean up session can be considered relevant in order to give back the right dignity to one of the most naturalistically relevant environments of Central Italy. For each field session a plethora of data can be acquired both onshore and underwater by diving operators. Therefore, the data management of a huge temporal and spatial variability can be remarkable. It can be made easier relying on artificial intelligence (AI) supporting geospatial databases for GIS analysis to be run for their role as decision-supporting tools. On this perspective AIs can be used to model environmental systems, greatly helping to reduce use conflicts and human-driven impacts, whilst understanding the ecological characteristics and related ecosystem functioning.

Seafloor mapping is crucial for sustainable Ocean management, but the distribution, drivers and origins of deep-sea biodiversity remain uncharted at global scales. The deep ocean is the largest and least-explored ecosystem on Earth, and the greatest source of unknown lifeforms. This con-tribution is firstly the story of a merge between exploration, science, education and technology for humankind cultural heritage advancement in one of the formally recognized protected areas of the Pacific Ocean. The data herein described are the outcome of a series of underwater surveys fi-nalized during the 2023 Exploration Campaign onboard E/V Nautilus, led by the Ocean Explo-ration Trust within the Papahānaumokuākea Marine National Monument, which is the largest conservation area established in the U.S. and one of the largest marine protected areas of the world. Our findings provide an advanced approach to scientific research combining the tradi-tional approach of marine sciences to the cultural and social dimension of local traditions, in or-der to empower the indigenous people in the underwater cultural heritage knowledge advance-ment process, aimed at deep-sea biodiversity detection and unexplored seafloor surveying. Be-side the high potential for this human dimension inclusion, the indigenous voices allowed to in-tegrate the mere scientific aspects commonly shared in every at-sea exploration, with the cultural values and practices respected from the local people who traditionally lived in sync with the Ocean for millennia. As a result, this approach allowed to enforce a trust relationship between the science world and some local representatives who joined the exploration onboard, providing an added value to the extant expertise.

Abstract We aim to describe the diagnosis and surgical management of urinary tract endometriosis (UTE). We detail current diagnostic tools including advanced transvaginal ultrasound, magnetic resonance imaging, and surgical diagnostic tools such as cystourethroscopy. While discussing surgical treatment options, we emphasize the importance of an interdisciplinary team, for complex cases that involve the urinary tract. While bladder DE is more straightforward in its surgical treatment, ureteral DE requires a high level of surgical skill. Specialists should be aware of the important entity of UTE due to the serious health implications for women. When UTE exists, it is important to work within a interdisciplinary radiological and surgical team.

China's gradually increasing assertiveness at the international level marked the beginning of several influential geopolitical projects. The biggest of these is the Belt and Road Initiative, which will be the subject of this post. The Chinese government initiated the BRI in 2013 to revive the historic Silk Road. The name of the new initiative was chosen based on well-known historical parallels, emphasizing the ideological component of China's current position. At the same time, neo-mercantilism prevails in China, and we can say that all roads lead to China, which means that the current nature of Chinese strategic planning corresponds to the increasingly important role of the state in international relations and strengthens its position in the world economy. The aim of the paper is to use the methods of analysis, synthesis, deduction, induction, comparison, and explanation to analyse Chinese investments that flow into various sectors worldwide, but especially into the countries participating in the Belt and Road Initiative from 2013 to the present. The largest such sector is the energy sector, which we will look at in more detail in the post. Finally, the contribution will be focused on predicting the development of further investments based on the available information as well as our own suggestions and recommendations to make them more efficient.

Process model discovery covers different methodologies to mine a process model from traces of process executions, and is gaining an important role in Artificial Intelligence research. Current approaches in the area, with few exceptions, focus on determining a model of the flow of actions only. However, in several contexts, (i) restricting the attention to actions is quite limitative, since the effects of such actions have to be analysed, too, and (ii) traces provide additional pieces of information, in the form of states (i.e., values of parameters possibly affected by the actions): for instance, in several medical domains traces include both actions and measurements of patients’ parameters. In this paper, we propose AS-SIM (Action-State SIM), the first approach able to mine a process model which comprehends two distinct classes of nodes, to capture both actions and states.

The progression of the recent COVID-19 pandemic surprised political authorities as well as scientists. The possibility to design powerful strategies for health care and preserving economic and social activities strongly relies on the capacity to monitor correctly the virus spreading and the immune response in the symptomatic and asymptomatic population. The available data relative to the first pandemic months indicate that the test reliability was progressively improved but also that the extremely variable methodologies used in the diagnostic studies generated data that are often not comparable. This condition prevents a simple metadata analysis for the identification of reliable diagnostics guidelines. Nevertheless, there are converging evidences that combinations of complementary approaches may enable more precise identification of virus infection. Furthermore, it appears that the similarities between SARS-CoV2 and the related types SARS-CoV1 and MERS that caused outbreaks in the last 20 years can be exploited to infer some information for which no direct evidence is still available

The main purpose of tissue engineering is to fabricate and exploit engineered constructs suitable for the effective replacement of damaged tissues and organs, and able to perfectly integrate with the host’s organism without eliciting any adverse reaction. Ideally, autologous materials represent the best option, but they are often limited due to the low availability of compatible healthy tissues. So far, one therapeutic approach relies on the exploitation of synthetic materials: they exhibit good features in terms of impermeability, deformability and flexibility, but present chronic risks of infections and inflammations. Alternatively, biological materials, including naturally derived ones and acellular tissue matrices of human or animal origin, can be used to induce cells growth and differentiation, which are needed for tissue regeneration: however, this kind of materials lacks satisfactory mechanical resistance and reproducibility, affecting their clinical application. In order to overcome the above-mentioned limitations, hybrid materials, which can be obtained by coupling synthetic polymers and biological materials, have been investigated with the aim to improve biological compatibility and mechanical features. Currently, the interest in these mate-rials is growing, but the ideal ones have not been found yet. The present review aims at exploring some applications of hybrid materials, with particular mention to urological and cardiovascular fields: in the first case, the efforts to find a construct that can guarantee impermeability, mechanical resistance and patency will be herein illustrated; in the second case, the search for impermeability, hemocompatibility and adequate compliance will be been disclosed.

In the Mediterranean area, vegetation dynamics and phenology analyzed over a long time can have an important role in highlighting changes in land use and cover as well as the effect of climate change. Over the last 30 years, remote sensing has played an essential role in bringing about these changes thanks to many types of observations and techniques. Satellite images are to be considered an important tool to grasp these dynamics and evaluate them in an inexpensive and multidisciplinary way thanks to Landsat and Sentinel satellite constellations. The integration of these tools holds a dual potential: on one hand, allowing to obtain longer historical series of reflectance data, while on the other hand, making data available with a higher frequency even within a specific timeframe. The study aims to conduct a comprehensive cross-comparison analysis of long-time series pixel values in the Mediterranean regions. For this scope comparisons between Landsat-7 (ETM+), Landsat-8 (OLI), and Sentinel-2 (MSI) satellite sensors were conducted based on surface reflectance products. We evaluated these differences using Ordinary Least Squares (OLS) and Major Axis linear regression (RMA) analysis on points extracted from over 15,000 images across the Mediterranean basin area from 2017 to 2020. Minor but consistent differences were noted, necessitating the formulation of suitable adjustment equations to better align Sentinel-2 reflectance values with those of Landsat-7 or Landsat-8. The results of the analysis are compared with the most used harmonization coefficients proposed in the literature, revealing significant differences. The root mean square deviation, the mean difference and the orthogonal distance regression (ODR) slope show an improvement of the parameters for both models used (OLS and RMA) in this study. The discrepancies in reflectance values lead to corresponding variations in the estimation of biophysical parameters, such as NDVI, showing an increase in the ODR slope of 0.3. Despite differences in spatial, spectral, and temporal characteristics, we demonstrate that integration of these datasets is feasible through the application of band-wise regression corrections for a sensitive and heterogeneous area like those of the Mediterranean basin area.

The carbohydrate antigen Sda is expressed on cells and secretions of the vast majority of Caucasians. The epitope is formed by a terminal GalNAc residue β4-linked to a α3-sialylated galactose. Different carbohydrate chains N- or O-linked to glycoproteins can be terminated by this epitope. The final step of Sda biosynthesis is catalyzed by the GalNAc transferase B4GALNT2. In this review, we will discuss the multifaceted aspects of B4GALNT2/Sda biology. In particular, we will see its implications in fertility and pregnancy, in susceptibility to infectious diseases, in chronic kidney diseases and in Duchene muscular dystrophy. In particular, we will show its regulation and prognostic implications in cancer.

The growth of two pairs of co-cultures (Escherichia coli/Geotrichum candidum, and Staphylococcus aureus/Geotrichum candidum) with a starter culture of lactic acid bacteria was studied in milk at temperatures related to artisanal cheesemaking ripening. For an inoculum of approximately 106 CFU/mL, LAB not only induced an early stationary phase of E. coli (two strains BR and PS2) and S. aureus (strains 2064 and 14733) but affected their death phase. G. candidum was found to be the subject of interactions with LAB within a given temperature range only partially. To develop a tertiary model for the growth curves of the populations, a one-step approach was used, combining two types of primary models (Huang and Gimenez and Dalgaard) with secondary square root models for growth rate and lag time. Furthermore, the reparametrized Gompertz-inspired function with the Bigelow secondary model was used to describe the death phase of the E. coli and S. aureus strains. The prediction ability of the growth of the H-GD tertiary model for co-cultures was cross-validated within the strains and data sets in milk and milk medium with 1 % NaCl.

Cholangiocellular carcinoma (CCA) is the second most common primary liver cancer, with increasing incidence worldwide and inadequate therapeutic options. Intra- and extrahepatic bile ducts have distinctly different embryonic origins and developmental behavior, and accordingly intra- and extrahepatic CCAs (ICC vs. ECC) are molecularly different. A promising strategy in oncotherapy is targeted therapy, targeting proteins that regulate cell survival and proliferation; such as the MAPK/ERK and PI3K/AKT/mTOR signaling pathways. Inhibitors of these pathways have been tested previously in CCA cell lines. However, these cell lines could not be clearly assigned to ICC or ECC, and results indicated apoptosis induction by targeted therapeutics. We tested targeted therapeutics (selumetinib, MK2206) in three defined ICC cell lines (HuH28, RBE, SSP25). We observed cooperative effects of dual inhibition of the two pathways, in accordance with inhibition of phospho-AKT and phospho-ERK1/2 expression. Proliferation was blocked more effectively with dual inhibition than with each single inhibition, but cell numbers did not drop below baseline. Accordingly, we observed G1-phase arrest, but not apoptosis (cleaved caspase-3, AIFM1 regulation, subG1-phase) or necroptosis (phospho-MLKL). We conclude that dual inhibition of MAPK/ERK and PI3K/AKT/mTOR pathways is highly effective to block proliferation of ICC cell lines, but therapy must certainly be supplemented with standard therapies.

The results of the most recent investigation of triterpenoid-based antiviral agents effective namely in the HIV-1 and HSV-1 treatment were reviewed and summarized. Several key historical achievements are included to stress consequences and continuity in this research. Most of the agents studied belong into a series of compound derived from betulin or betulinic acid, and their synthetic derivative called bevirimat. A termination of clinical trials of bevirimat in the Phase IIb initiated a search for more successful compounds partly derived from bevirimat or designed independently of bevirimat structure. Surprisingly, a majority of bevirimat mimics are derivatives of betulinic acid, while other plant triterpenoids, such as ursolic acid, oleanolic acid, glycyrrhetinic acid or other miscellaneous triterpenoids, are relatively rarely involved in a search for novel antiviral agent. Therefore, this review article is divided into three parts based on the leading triterpenoid core structure.

Extensive evidence indicates that activation of P2X7 receptor (P2X7R), an ATP-gated ion channel highly expressed in immune and brain cells, is strictly associated with the release of extracellular vesicles. Through this process, P2X7R-expressing cells regulate non-classical protein secretion and transfer bioactive components to other cells, including misfolded proteins, participating in inflammatory and neurodegenerative diseases. In this review, we summarize and discuss the studies addressing the impact of P2X7R activation on extracellular vesicle release and their activities.

Besides common skin pathogens, acute focal lymphadenitis in humans can be caused by a zoonotic pathogen in rare cases. Furthermore, it can develop in absence of any direct or indirect contact with infected animal in cases when the microorganism is transmitted by vector. This clinical entity is rare, and therefore not easily recognized in most regions, yet many zoonotic illnesses are considered emerging or re-emerging nowadays. Focal zoonotic vector-borne lymphadenitis and its numerous causative agents with their variegated clinical manifestations have been described in some case reports and small case series. Therefore, we tried to summarize those data in this narrative overview, with the aim to rise clinical awareness, which could improve clinical outcomes. This overview briefly covers reported pathogens, their vectors and geographic distribution, as well as their main clinical manifestations, diagnostic possibilities and recommended therapy. Vector-borne tularemia, plague, bartonellosis, rickettsioses, borreliosis and Malayan filariasis are mentioned. According to the existing data, when acute focal bacterial vector-borne zoonotic lymphadenitis is suspected, in severe or complicated cases it seems prudent to apply combined aminoglycoside (or quinolone) plus doxycycline as an empirical therapy, pending definite diagnostic results. In this field the „one health approach” and further epidemiological and clinical studies are needed.

The interactions of metal ions with fulvic acids resulted in changes in the particle size and charge. Particle size distribution was trimodal for fulvic acids, bimodal for fulvic complexes with calcium and magnesium, and copper-fulvic complexes had only one size fraction. The compensation of negative charge of carboxylic and phenolic functional groups by positive charged metal ions resulted in the increase in zeta potential which was getting closer to zero in the case of copper-fulvic complexes. However, all metal humic complexes behaved as colloidally unstable which resulted in visually observable sedimentation. Calorimetric measurements provided positive values of changes in enthalpy which indicated endothermic processes. In contrast quantum chemical calculations as well as experiments with model compounds provided negative values indicated exothermic processes. Changes in Gibbs energy were determined as negative and changes in entropy as positive which meant spontaneous processes.

O2 is essential for the life of eukaryotic cells. The ability to sense oxygen availability and initiate a response to adapt the cell to changes in O2 levels is a fundamental achievement of evolution. The key switch for adaptation consists of the transcription factors HIF1A, HIF2A and HIF3A. Their levels are tightly controlled by O2 through the involvement of the oxygen-dependent prolyl hydroxylase domain-containing enzymes (PHDs/EGNLs), the von Hippel-Lindau tumour suppressor protein (pVHL) and the ubiquitin-proteasome system. Furthermore, HIF1A and HIF2A are also under the control of additional post-translational modifications (PTMs) that positively or negatively regulate the activities of these transcription factors. This review focuses mainly on two PTMs of HIF1A and HIF2A: phosphorylation and acetylation.

3D bioprinting is the process of manipulating cell-laden bioinks to fabricate living structures. 3D bioprinting techniques have brought considerable innovation in biomedicine, especially in the field of tissue engineering, allowing the production of 3D organ and tissue models for in vivo transplantation purposes or for in-depth and precise in vitro analyses. Natural-derived hydrogels, especially those obtained from the decellularization of biological tissues, are promising bioinks for 3D printing purposes, as they present the best biocompatibility characteristics. Despite this, many natural hydrogels do not possess the necessary mechanical properties to allow a simple and immediate application in the 3D printing process. In this review, we focus on the bioactive and mechanical characteristics that natural hydrogels may possess to allow efficient production of organs and tissues for biomedical applications, emphasizing the reinforcement techniques to improve their biomechanical properties.

Introduction Infections caused by multidrug-resistant bacteria (MDR) occur more frequently after pancreaticoduodenectomy (PD) compared to other abdominal surgeries, and infective complications are a leading cause of postoperative morbidity following PD. Pre-operative biliary stent (PBS) placement often leads to biliary contamination, which in turn plays a significant role in postoperative infections. The aim of this study is to evaluate the impact of MDR contamination on short-term postoperative outcomes in patients undergoing PD and to examine the relationship between MDR bacteria, PBS, and bile contamination. Methods This is a retrospective study based on a prospectively maintained database comprising 825 consecutive patients who underwent pancreaticoduodenectomy (PD) between January 2010 and December 2020 at our center. All procedures were conducted with a standardized resection by a dedicated group of surgeons in a specialized pancreatic surgery unit, and the patients were managed according to the same perioperative enhanced recovery protocol. Results MDR bacteria were present in 17.5% of bile cultures, exclusively within the stented group. In our multivariate analysis, the development of a major postoperative complication (MPC) was correlated with the presence of MDR bacteria in the bile (OR 1.66, 95% CI: 1.1-2.52; p = 0.02). MDR bacteria were detected early in the surgical drainage in 144 out of 825 patients (12.1%), with 72.2% having a previous biliary stent placement and 27.8% without stents (p < 0.001). In our multivariate analysis, the development of an MPC was associated with the presence of MDR bacteria in the drainage (OR=1.81, 95% CI: 1.21-2.73, p= 0.0042). Conclusions We demonstrated that MDR contamination worsens the short-term outcomes of patients undergoing PD. Specifically, when MDR bacteria are present in both the bile and drainage, there is a statistically significant increase in the incidence of major postoperative complications (MPC). Our data suggest that the majority of MDR surgical site infections stem from biliary contamination resulting from the placement of a pre-operative biliary stent (PBS).

Malaria remains an important cause of death, especially in sub-Saharan Africa with about 228 million malaria cases worldwide and an estimated 405,000 deaths in 2019. Currently, malaria is diagnosed in the health facility using a microscope (BS) or rapid malaria diagnostic test (MRDT) and with area where these tools are inadequate the presumptive treatment is performed. Apart from that self-diagnosis and treatment is also practiced in some of the households. With the high-rate self-medication on malaria drugs, this study aimed at computing the most significant features using feature selection methods for best prediction of malaria in Tanzania that can be used in developing a machine learning model for malaria diagnosis. A malaria symptoms and clinical diagnosis dataset were extracted from patients’ files from four (4) identified health facilities in the regions of Kilimanjaro and Morogoro. These regions were selected to represent the high endemic areas (Morogoro) and low endemic areas (Kilimanjaro) in the country. The dataset contained 2556 instances and 36 variables. The random forest classifier a tree based was used to select the most important features for malaria prediction. Regional based features were obtained to facilitate accurate prediction. The feature ranking as indicated that fever is universally the most influential feature for predicting malaria followed by general body malaise, vomiting and headache. However, these features are ranked differently across the regional datasets. Subsequently, six predictive models, using important features selected by feature selection method, were used to evaluate the features performance. The features identified complies with malaria diagnosis and treatment guideline provided with WHO and Tanzania Mainland. The compliance is observed so as to produce a prediction model that will fit in the current health care provision system in Tanzania.

The genus Fusarium includes several agronomically important and toxin-producing species, that are worldwide distributed and can cause a wide range of diseases. Crown and stalk rots and grain infections are among the most severe symptoms that Fusarium spp. can cause on maize. The disease development usually occurs during germination, but it may also affect the later phases of plant growth. The purpose of this study was to investigate the diversity and the patho-genicity of 41 isolates recovered from symptomatic seedlings collected in Northern Italy, and from seeds with five different geographical origins during 2019 and 2020. The pathogenicity was tested and confirmed on 23 isolates causing rotting on maize seedlings. A multi-locus phylogeny analysis, based on four genomic loci (tef1-α, rpb2, calm and tub2), was performed for 23 repre-sentative isolates. Representative isolates were identified as species belonging to three species complexes (SC). Fusarium verticillioides and F. annulatum in the F. fujikuroi SC. Fusarium commune was identified in the F. nisikadoi SC, and three different lineages were found in the Fusarium ox-ysporum SC. This study reports F. annulatum, and two lineages of the Fusarium oxysporum SC as maize pathogens for the first time in Italy.

The age-related loss of muscle mass and strength is referred to as “sarcopenia”. The combined effect of sarcopenia and osteoporosis is a devastating threat to the old adult, accounting for reduced mobility, risk for falls and subsequent fractures. In previous studies, we observed a high degree of inter-individual variability of paraspinal muscle fatty infiltration, one most relevant index of muscle wasting. This aspect solicited us to develop a computerized method to quantitatively characterize muscle fatty infiltration in aging and diseases. Magnetic resonance images of paraspinal muscles from 58 women of different age (age range 23-85 years) and physio-pathological status (healthy young, pre-menopause, post-menopause, and os-teoporosis), were used to set up the method. It is based on fractal analysis of lean muscle area (contractile muscle) to estimate muscle fatty infiltration. In particular, lacunarity was computed by parameter β from our hyperbola model function, used to fit the GBA (gliding box algorithm) curvilinear plot. Succolarity was estimated by parameter µ, for the four main directions, through an algorithm implemented on purpose. Results show that fractal lacunarity, by quantifying muscle fatty infiltration, can discriminate be-tween osteoporosis and healthy aging while succolarity can separate the other three groups showing similar lacunarity. Therefore, fractal features of contractile muscle, by measuring fatty infiltration, can represent good indices of sarcopenia in aging and disease.

In this study, the analysis of the changes of SARS-CoV-2 Orf3a protein during pandemic is reported. Orf3a, a conserved protein in the Coronaviruses, is involved in virus replication and release. A software workflow able to carry out a quick, systematic and repeatable screening of the SARS-CoV-2 genome isolates to detect protein mutations, was utilized to scan 70,752 high-quality SARS-CoV-2 genomes available in GISAID databank at the end of August 2020. All ORF3a mutations in the virus genomes were grouped according to the collection date interval and over the entire data set. The considered intervals were start of collection-February, March, April, May, June, July and August 2020. The top five most frequent variants were examined within each collection interval. Overall, seventeen variants have been isolated. Ten of the seventeen mutant sites occur within the transmembrane (TM) domain of ORF3a and are in contact with the central pore or side tunnels. The other variant sites are in different places of the Orf3a structure. Within the entire sample, the five most frequent mutations are V13L, Q57H, Q57H+A99V, G196V and G252V. The same analysis identified 28 sites identically conserved in all the genome isolates. These sites are possibly involved in stabilization of monomer, dimer, tetramerization and interaction with other cellular components. The results here reported can be helpful to understand virus biology and to design new therapeutic strategies.

Gastric Cancer (GC) is the fifth most frequently diagnosed malignant tumor and the third cause of cancer mortality worldwide. For advanced GC, a large number of novel drugs and combinations have been tested, but results are still disappointing and the disease incurable in the majority of cases. In this regard, it is critical to investigate the molecular mechanisms underlying GC development. Angiogenesis is one of the hallmarks of cancer with a fundamental role in GC growth and progression and ramucirumab, a monoclonal antibody binding to vascular endothelial growth factor-2 (VEGFR-2) is approved in the treatment of advanced and pretreated GC. However, no predictive biomarkers for ramucirumab have been identified so far. MicroRNAs (miRNAs) are a class of evolutionally conserved single-stranded noncoding RNAs playing an important role, via post-transcriptional regulation, in essentially all biologic processes such as cell proliferation, differentiation, apoptosis, survival, invasion, and migration. Notably, in our review, we focused on miRNAs involved in angiogenic pathways in GC. Moreover, we evaluated the possible prognostic and predictive role of angiogenesis-related miRNAs as novel biomarkers of GC.

Microplastics are small plastic pieces with sizes less than 5 mm. They are becoming a global concern due to the potential risk to human health. The potential risks of microplastics may be greater for infants because they do not have sufficiently developed metabolizing enzymes, have a lower ability to remove them, high sensitivity of target organs. Infants should be breastfed for the first six months of life. Breast milk is considered to be the most complete and suitable source of nutrition. However, if breastfeeding during this period is not possible, it is necessary to use formulas designed for infant initial feeding. Infants may be exposed to higher levels of MPs through infant foods or plastics products. The aim of this study is to describe the possible sources of exposure to microplastics such as human placenta, plastic feeding bottles, toys as well as the presence of released microplastics in infants feces, breast milk and infant formulas. There is still not enough data available from the studied area. Therefore, it is necessary to pay increased attention to minimizing the negative effects of microplastics on human health.

Beer is a fermented beverage with a history as old as human civilization and its productive process has been spread all around the world becoming unique in every country and iconic of entire populations. Ales and lagers are by far the most common beers; however, the combination of raw materials, manufacture techniques and aroma profiles are almost infinite, so it is not surprising to notice that there is a large amount of different beer styles, each of them with unique characteristics. Nowadays, diversification is becoming increasingly important in the brewing market and the brewers are continuously interested in improving and extending the already wide range of products, especially in craft brewery. One of the major components that can have a deep impact on the final product is yeast, since it is able to convert carbohydrates in wort, especially maltose and maltotriose, into ethanol, carbon dioxide and other minor aroma-active compounds. Saccharomyces cerevisiae (top‐fermenting yeasts used to produce ales) and Saccharomyces pastorianus (cryotolerant bottom‐fermenting hybrids between S. cerevisiae and Saccharomyces eubayanus responsible for the fermentation of lagers) are most used in breweries. However, an increasing number of different yeast starter cultures are commercially available, to improve the production efficiency also at relative low temperatures and to obtain desirable and diversified aroma profiles avoiding undesired compounds. Four main genetic engineering-free trends are becoming popular in craft brewing yeast development: 1) the research for novel reservoirs as source of new performant S. cerevisiae yeasts; 2) the creation of synthetic hybrids between S. cerevisiae and Saccharomyces non-cerevisiae in order to mimic lager yeasts by expanding their genetic background; 3) the exploitation of evolutionary engineering approaches; 4) the usage of non-Saccharomyces yeasts either in co-coculture or in sequential fermentation with S. cerevisiae. In the present work we summarized pro and contra of these approaches and provided an overview on the most recent advances on how brewing yeast genome evolved and domestication took place. Finally, we delineated how the correlations maps between genotypes and relevant brewing phenotypes can assist and further improve the search for novel craft beer starter yeasts.

The leading role of Italy in the cultivation of durum wheat stimulated intense breeding activities in the country from the beginning of the 20th century, much earlier than any other country involved in durum wheat production. Older, genetically more heterogeneous landraces became replaced with new highly productive, superior quality varieties, and this led an inevitable reduction in overall genetic diversity among new cultivars, which makes the genetic variability of the old cultivars preserved particularly valuable and important. The aim of this paper was to assist future breeding programmes by providing a detailed description of the history of durum wheat breeding in Italy and of the changes in yield, quality and related traits that subsequently occurred, starting from the most diffuse landraces present between 1900 and 1920 up until the present day. The parallel evolution of breeding techniques, breeding goals and agricultural systems in this period is also described, and some future breeding goals suggested. In the current context of climate change and of rapidly mutating pathogen populations, preserving the yield level with the continuous introduction of new cultivars by exploiting the reservoir of largely unused genetic variation stored in old cultivars and landraces could be as important as increasing grain yield and quality.

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

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

Porphyrinic photosensitizers (PSs) and their nano-sized polymer-based carrier systems are required to exhibit low dark toxicity, avoid side effects, and ensure high in vivo tolerability. Yet, little is known about the intracellular fate of PSs during the dark incubation period and how it is af-fected by nanoparticles. In a systematic study, high resolution magic angle spinning NMR spectroscopy combined with statistical analyses was used to study the metabolic profile of cultured HeLa cells treated with different concentrations of the PS chlorin e4 (Ce4) alone or encapsulated in carrier systems. For the latter, either polyvinylpyrrolidone (PVP) or the micelle forming polyethylene glycol (PEG)-polypropylene glycol triblock copolymer Kolliphor P188 (KP) were used. Diffusion edited spectra indicated Ce4 membrane localization evidenced by Ce4 concentration dependent chemical shift perturbation of the cellular phospholipid choline resonance. The effect was also visible in the presence of KP and PVP, but less pronounced. The appearance of the PEG resonance in the cell spectra pointed towards cell internalization of KP whereas no conclusion could be drawn for PVP that remained NMR-invisible. Multivariate statistical analyses of the cell spectra (PCA, PLS-DA and oPLS) revealed a concentration-dependent metabolic response upon exposure to Ce4 that was attenuated by KP and even more by PVP. Significant Ce4-concentration dependent alterations were mainly found for metabolites involved in the tricarboxylic acid cycle and the phosphatidylcholine metabolism. The data underline an important protective role of the polymeric carriers following cell internalization. Moreover, the current study allowed - to our knowledge for the first time - to trace the intracellular PS localization on an atomic level by NMR methods.

Background: Neuromuscular electrical stimulation (NMES) has beneficial effects on physical functions in Multiple Sclerosis (MS) patients. However, the neurophysiological mechanisms underlying these functional improvements are still unclear. This study aims at comparing acute responses in spinal excitability, as measured by soleus Hoffmann reflex (H-reflex), between MS patients and healthy individuals, following three experimental conditions involving the ankle planta flexor muscles: 1) passive NMES (pNMES); 2) NMES superimposed to isometric voluntary contraction (NMES+); and 3) isometric voluntary contraction (ISO). Methods: 20 MS patients (MSp) and 20 healthy individuals as control group (CG) took part in a single experimental session. During each condition, participants performed 15 repetitions of 6 seconds at 20% of maximal voluntary isometric contraction, with 6 seconds of recovery between repetitions. Before and after each condition, H-reflex amplitudes were recorded. Results: In MSp, H-reflex amplitude did not change following any experimental condition (ISO: p = 0.506; pNMES: p = 0.068; NMES+: p = 0.126). In CG, H-reflex amplitude significantly increased following NMES+ (p = 0.01), decreased after pNMES (p = 0.000) and was unaltered following ISO (p = 0.829). Conclusion: the different H-reflex responses between MS and CG might reflect a reduced ability of MS patients in modulating spinal excitability.

The discovered light modulation capabilities of diatom silicious valves make them an excellent toolkit for photonic devices and applications. In this work, a reproducible surface-enhanced Raman-scattering (SERS) enhancement was achieved with hybrid substrates employing diatom silica valves coated with an ultrathin uniform gold film. Three structurally different hybrid substrates, based on the valves of three dissimilar diatom species, have been compared to elucidate the structural contribution to SERS enhancement. The comparative analysis of obtained results showed that substrates containing cylindrical Aulacoseira sp. valves achieved the highest enhancement up to 14-fold. Numerical analysis based on the frequency domain finite element method was carried out to supplement the experimental results. Our results demonstrate that diatom valves of different shapes can enhance the SERS signal, offering a toolbox for SERS-based sensors, where the magnitude of the enhancement depends on valve geometry and ultrastructure.

Mycotoxins are secondary metabolites produced by filamentous fungi associated to a variety of acute and chronic foodborne diseases. Current toxicology studies mainly rely on monolayer cell cultures and animal models, which are undeniably affected by several limitations. To bridge the gap between the current in vitro toxicology approach and the in vivo predictivity of the data, we here investigated the cytotoxic effects induced by the mycotoxins sterigmatocystin (STE), ochratoxin A (OTA) and patulin (PAT) on different 2D and 3D cell cultures. We focused on human tumours (neuroblastoma SH-SY5Y cells, and epithelial breast cancer MDA-MB-213 cells) and healthy cells (bone marrow derived mesenchymal stem cells, BM-MSC, and umbilical vein endothelial cells, HUVECs). Cytotoxicity of STE, OTA, and PAT was determined after 24, 48 and 72 h of exposure by ATP assay in both culture models. 3D spheroids morphology was also analysed using the MATLAB-based open-source software AnaSP. Our results highlighted how each cell line and different culture models showed specific sensitivities, reinforcing the importance of using more complex models for toxicology studies and a multiple cell line approach for an improved and more comprehensive risk assessment.

Mass mortality events and anthropogenic impacts were increasingly documented affecting Paramuricea clavata (Risso, 1826) during the last decades. These impacts enhance the settling of epibiontic organisms on the injured colonies. The epibiosis was studied by photographic sampling carried out on the granitic outcrops of the Tavolara Channel within the Tavolara-Punta Coda Cavallo Marine Protected Area (NE Sardinia) between 2017-2023 at 35-55 m. The number of colonies and percent surface involved in epibiosis, the specific richness of the epibiontic community and the temporal evolution of the phenomenon were investigated. Almost all the investigated gorgonians (93%) showed parts involved in epibiosis, with a high percentage of covering (one-third of the surface). Out of the 37 epibiontic species recorded, the most recurrent described an ecological succession dominated by hydrozoans, sponges, bryozoans, serpulids and the parasitic soft coral Alcyomiun coralloides. Nevertheless, single colonies studied through time revealed the unpredictability of the colonization process. The peculiar habitat of a high naturalistic value of the granitic outcrops hosting the P. clavata forests demonstrates a widespread suffering condition, supported both by environmental and anthropogenic sources of stress. Such considerations make it necessary to review the current zonation of the area, where the actual vulnerability and usability evaluations are based on obsolete information.

Weight increase after tonsillectomy has been reported in different studies and systematic reviews. However, the odds of a child being overweight or obese after tonsillectomy were no other than before surgery, according to a few studies. This systematic review aimed to analyze the impact of adenotonsillectomy (TA) on weight gain and to identify subgroups of children and adolescents at risk of obtaining weight gain. A systematic search was performed, including studies published in the last ten years. The PICO framework was used in the selection process, and evidence was as-sessed using the GRADE system. A total of 26 studies were included, and moderate-high level quality ones showed that children who underwent TA could present an increase in BMI z-score. However, this weight gain was significant in individuals younger than six years old and was considered a catch-up growth in subjects who were underweight at baseline. In contrast, in nor-mal-weight or overweight individuals, TA did not lead to overweight per se. At the same time, diet changes and overfeeding seem to not have a leading role in weight gain. In conclusion, TA may not be an independent risk factor for unfavorable weight gain in children; however, individuals who were underweight pre-operatively or younger than six years reported more weight gain after TA than expected.

Sustainability in material purchasing is a growing area of research. Goods purchasing decisions strongly affect transportation path flows, vehicle consolidation, inventory levels and related obsolescence costs. Within a global sourcing context, companies experience the need of new decision making approaches capable to consider a large variety of factors, also linked with society and environment. Environmental impact assessment has become a key requirement for materials purchasing and transportation decisions since global warming is a rising concern both in academic and industrial researches. In fact, it is well known that the freight transport industry is responsible for large amounts of carbon emissions contributing to global warming. In this paper, we initially analyse and compare the environmental economic policies established by the International Governments in relation to the carbon trading systems adopted. Then, we develop a multi-objective lot sizing approach useful in practice to define the sustainable quantity to purchase when a Cap and Trade mitigation policy is present. We further analyse the model behaviour according to different carbon price values by demonstrating that carbon prices are still far too low to motivate managers towards sustainable purchasing choices.

The radiosensitivity of biological systems is strongly affected by the system oxygenation. On the nanoscopic scale and molecular level, this effect is considered to be strongly related to the indirect damage of radiation. Even though particle track radiolysis has been the object of several studies, still little is known about the nanoscopic impact of target oxygenation on the radical yields. We present here an extension of the chemical module of the Monte Carlo particle track structure code TRAX, taking into account the presence of dissolved molecular oxygen in the target material. The impact of the target oxygenation level on the chemical track evolution and the yields of all the relevant chemical species is studied in water under different irradiation conditions: different linear energy transfer (LET) values, different oxygenation levels, and different particle types. Especially for low LET radiation, a large production of two highly toxic species (HO₂^• and O₂^•− ), which are not produced in anoxic conditions, is predicted and quantified in oxygenated solutions. The remarkable correlation between the HO₂^• and O₂^•− production yield and the oxygen enhancement ratio observed in biological systems suggests a direct or indirect involvement of HO₂^• and O₂^•− in the oxygen sensitization effect. The results are in agreement with available experimental data and previous computational approaches. An analysis of the oxygen depletion rate in different radiation conditions is also reported.

Cash crops are agricultural crops intended to be sold for profit as opposed to subsistence crops, meant to support the producer, or to support livestock. Since cash crops are intended for future sale, they translate into large financial value when considered on a wide geographical scale, so their production directly involves financial risk. At a national level, extreme weather events including destructive rain or hail, as well as drought, can have a significant impact on the overall economic balance. It is thus important to map such crops in order to set up insurance and mitigation strategies. Using locally generated data -such as municipality-level records of crop seeding- for mapping purposes implies facing a series of issues like data availability, quality, homogeneity etc. We thus opted for a different approach relying on global datasets. Global datasets ensure homogeneity and availability of data, although sometimes at the expense of precision and accuracy. A typical global approach makes use of spaceborne remote sensing, for which different land cover classification strategies are available in literature at different levels of cost and accuracy. We selected the optimal strategy in the perspective of a global processing chain. Thanks to a specifically developed strategy for fusing unsupervised classification results with environmental constraints and other geospatial inputs including ground-based data, we managed to obtain good classification results despite the constraints placed. The overall production process was composed using ``good-enough" algorithms at each step, ensuring that the precision, accuracy, and data-hunger of each algorithm was commensurate to the precision, accuracy, and amount of data available. This paper describes the tailored strategy developed on the occasion as a cooperation among different groups with diverse backgrounds, a strategy which is believed to be profitably reusable in other, similar contexts. The paper presents the problem, the constraints and the adopted solutions; it then summarizes the main findings including that efforts and costs can be saved on the side of Earth Observation data processing when additional ground-based data are available to support the mapping task.

Abstract The relationship between cancer and neurodegeneration has spurred extensive scientific discourse, challenging their historical classification as distinct disorders. While cancer signifies uncontrolled cellular proliferation and neurodegeneration marks progressive neuronal loss, recent insights highlight intriguing interconnections between these seemingly disparate conditions. Cancer entails perpetual signaling for growth, evasion of growth inhibitors, resistance to cell death, acquisition of replicative immortality, stimulation of blood vessel growth (angiogenesis), and initiation of invasion and metastasis. Conversely, investigations emphasize disrupted cellular energy regulation and evasion of immune surveillance as key traits arising from genome instability, mutations, and inflammation driving tumorigenesis. Neurodegeneration involves neuronal malfunction and depletion, synaptic impairment, and protein abnormalities aggregations contributing to muscle atrophy and cognitive deficits. Varied clinical studies underscore contrasting correlations between cancer and neurodegeneration, hinting at mirrored molecular pathways that foster cell resilience or vulnerability. Research explores cellular signaling in tumorigenesis, shared with neurodegenerative disorders. Aberrant expression or mutations in crucial genes implicated in neurodegeneration also surface in cancer contexts. Debates persist on the nature of the relationship between cancer and neurodegeneration, contemplating inverse associations or shared pathways. Understanding their complex interplay, encompassing genetics, cellular mechanisms, and environmental influences, remains pivotal in unraveling their connections. This review explores the intriguing perspective that neurodegeneration and cancer might share fundamental genetic links, delving into potential implications for their onset and progression.

Visual exploration of complex data helps interpretation, especially in the case of omics data analysis in life sciences and clinical research. Generating and analysing omics data requires bioinformatic skills, while they are interpreted by domain experts, for whom parsing large and complex data structures may be challenging. However, outcomes of visual analytics are often difficult to quantify, which emphasises precision and reproducibility, especially for research on human diseases. Here, we propose a workflow combining a reproducible computational environment with a dedicated visualisation functionality for systems biology diagrams. By linking the Galaxy with the MINERVA Platform, we visualise and explore COVID-19 transcriptomic data to demonstrate the utility of our workflow. Visualised data recapitulate findings of the original publication and offer new insights about the COVID-19 pathology. Our results offer a blueprint for quick prototyping of computational workflows that facilitate communication and exploration of complex data in biomedical research.

In 2020-2021, the second massive dissemination of a highly-pathogenic avian influenza (HPAI) of H5Nx subtype occurred in Europe. During this period, the virus caused numerous outbreaks in poultry, including in the Czech Republic. In the present study, we provide an insight into the genetic variability of the Czech/2021 (CZE/2021) H5N8 viruses to determine the relationships between strains from wild and domestic poultry and to infer transmission routes between the affected flocks of commercial poultry. For this purpose, whole genome sequencing and phylogenetic analysis of 70 H5N8 HPAI genomes representing 79.7% of the cases were performed. All CZE/2021 H5N8 viruses belonged to the 2.3.4.4b H5 lineage and circulated without reassortment, retaining the A/chicken/Iraq/1/2020 H5N8-like genotype constellation. Phylogenetic analysis suggested frequent local transmission of H5N8 HPAI from wild birds to minor poultry and extensive farm-to-farm spread among commercial poultry farms. In addition, the analysis suggested one cross-border transmission event. Indirect transmission via contaminated materials was considered the most likely source of infection. Improved biosecurity and increased collaboration between the field veterinarians and the laboratory are essential to limit the local spread of the virus and to reveal and interrupt critical routes of infection.

Alexithymia as the inability to describe one's own feelings, is being increasingly researched. According to contemporary psychodynamic theories, negative emotions cannot be adequately named and externalized, but remain trapped in the body. Recent research shows the connection of alexithymia with numerous somatic diseases. Diabetes mellitus type 2 and obesity represent a great challenge in treatment, and the psychological profiles in these diseases are being studied more and more often. Therefore, alexithymia enters the focus of some research as one that could play a significant role namely in these diseases as the factor that makes a difference. The aim of this paper is a review of the literature with the purpose of understanding the current knowledge about the interconnection between alexithymia, obesity and type 2 diabetes mellitus.

In 2021/2022, the re-emergence of highly pathogenic avian influenza (HPAI) occurred in Europe. The outbreak was seeded from two sources, resident and reintroduced viruses, which is unprecedented in the recorded history of avian influenza. The dominating subtype was H5N1, representing a reversion to the original A/goose/Guangdong/1/1996-like subtype combination. In this study, we present a whole genome sequence and a phylogenetic analysis of 57 H5N1 HPAI and two low pathogenic avian influenza (LPAI) H5N1 strains collected in the Czech Republic during 2021/2022. Phylogenetic analysis revealed close relationships between H5N1 genomes from poultry and wild birds and secondary transmission in commercial geese. The genotyping showed considerable genetic heterogeneity among Czech H5N1 viruses with six different HPAI genotypes, three of which were apparently unique. In addition, second-order reassortment relationships were observed with the direct involvement of co-circulating H5N1 LPAI strains. The genetic distance between Czech H5N1 HPAI and the closest LPAI segments available in the database illustrates the profound gaps in our knowledge of circulating LPAI strains. The changing dynamics of HPAI in the wild may increase the likelihood of future HPAI outbreaks and present new challenges in poultry management, biosecurity, and surveillance.

Fanconi anemia (FA) patients display an exacerbated risk of oral squamous cell carcinoma (OSCC) and precursor lesions at young ages, mainly at the oral cavity. As patients have defects in DNA repair mechanisms, standard-of-care treatments to OSCC such as radiotherapy and chemotherapy give rise to severe toxicities. New methods for early diagnosis are urgently necessary to allow treatments in early disease stages and achieve better clinical outcomes. We have conducted a prospective, longitudinal study whereby liquid biopsies from sixteen lesion/tumor-free patients were analyzed for the presence of mutations in cancer genes. DNA from saliva and plasma were sequentially collected and deep-sequenced, and the clinical evolution followed during a median time of around 2 years. In 9/16 FA patients we detected mutations in cancer genes (mainly TP53) with molecular allele frequencies (MAF) down to 0.07 %. Importantly, all patients having mutations and clinical follow-up data after mutation detection (n=6) developed oral precursor lesions or OSCC. Lead-time between mutation detection and tumor diagnosis ranged from 23 to 630 days. Strikingly, FA patients without mutations display significantly lower risk of developing precursor lesions or OSCC. Therefore, our diagnostic approach could help to stratify FA patients into risk groups, which would allow closer surveillance for OSCC or precursor lesions.

Global food waste has a huge impact on the environment, as it is a source of greenhouse gas (GHG) emissions and wasted natural resources. Across the world, over 30% of food is lost or wasted each year. Aside from this, food industry, as well, is one of the biggest sources of agro-industrial waste and by-products, which can be valorized and used for different purposes. Such waste is a good source of bioactive organic compounds which can be extracted without al-tering their properties, where deep eutectic solvents (DESs) can serve as green solvents and excel-lent replacement for volatile organic solvents. Isolated compounds can be used in innovative food production, chemical production, cosmetics and other industries. DESs have attracted extraordi-nary attention due to their advantages such as environmental friendliness, availability and easy preparation, easy handling and utilization of non-toxic components for their formation. Due to those properties, they are a greener alternative to classic organic solvents for many processes, in-cluding extractions. In this paper, we review the utilization of deep eutectic solvents as potential green media for the extraction of organic compounds such as polyphenols, carbohydrates, pro-teins, alkaloids from by-products of the food industry and agro-industrial-waste.

Background: Molecular nuclear medicine, due to hybrid imaging camera systems and new tailored radiopharmaceuticals, has been gained a clinical relevance for diagnosis, therapy and follow-up of solid tumors. Despite numerous literature studies, many new radiopharmaceuticals for imaging tumor microenvironment, have not yet been used, routinely, in oncological clinical practice to monitor treatments. This is due to poor comparability of published studies, due to poor design and methodology, heterogeneous population and prevalence of preclinical studies. Methods: In this systematic review, we described the use of radiopharmaceuticals for evaluation of tumor treatment response by targeting microenvironment. We reviewed studies published from 2000 to 2020, to provide an updated status of research in this topic. Results: There is a growing role of radiopharmaceuticals and nuclear medicine imaging techniques in the management of cancer treatments, especially immunotherapy. Of the 24 papers included, 16 were preclinical studies. Conclusions: New radiopharmaceuticals could have an excellent impact in molecular imaging, leading to better diagnosis and important clinical information for therapy decision making and follow-up of cancer treatments in different solid tumors. Recently developed radiopharmaceuticals may provide great advantage to improve personalized medicine for patients with a great cost-effectiveness ratio.

Since alternative methods (AAs), such as in vitro cultures, organs in silico, or mathematical methods, are not fully able to reproduce the complexity of the human organism, particularly neu-ral processes, and brain structures, animal experimentation remains the only way in which re-search can obtain the necessary knowledge to suggest drug therapies or targeted therapeutic in-terventions. Particularly in neuroscience, transgenic animals allow us to model neurological dis-eases, study the relationship between the brain and behavior, and decipher the function of genes involved in pathological conditions. However, it should never be forgotten that animals are "sen-tient beings" capable of feeling pleasure and pain (Art. 13 of the 2007 Lisbon Treaty). For this rea-son, it is crucial to prioritize the welfare of animals involved in testing by considering their phys-ical, psychological, adaptive, and relational well-being. This is where the concept of a Culture of Care comes in, where the responsibility of care extends beyond the veterinary aspects to include everything that can safeguard the welfare of animals before, during, and after experimentation. This chapter explains the advantages of using the animal model while practicing the culture of care in neuroscience, as both animals and research outcomes benefit from this approach.

As many if not most ligands at G protein-coupled receptor antagonists are inverse agonists, we have systematically reviewed inverse agonism at the nine adrenoceptor subtypes. Except for β3-adrenoceptors, inverse agonism has been reported for each of the adrenoceptor subtypes, most often for β2-adrenoceptors, including endogenously expressed receptors in human tissues. As with other receptors, detection and degree of inverse agonism depends on the cells and tissues under investigation, i.e. is greatest when the model has a high intrinsic tone/constitutive activity for the response being studied. Accordingly, it may differ between parts of a tissue, for instance atria vs. ventricles of the heart, and within a cell type between cellular responses. The basal tone of endogenously expressed receptors often is low, leading to less consistent detection and smaller extent of observed inverse agonism. The extent inverse agonism depends on specific molecular properties of a compound but clusters by chemical class. While inverse agonism is a fascinating facet in attempts to mechanistically understand observed drug effects, we are skeptical whether an a priori definition of extent of inverse agonism in the target product profile of a developmental candidate is a meaningful option in drug discovery and development.

Italy was the first country in Europe which imposed control measures of travel restrictions, quarantine and contact precautions to tackle the epidemic spread of the novel coronavirus (SARS-CoV-2) in all its regions. While such efforts are still ongoing, uncertainties regarding SARS-CoV-2 transmissibility and ascertainment of cases make it difficult to evaluate the effectiveness of restrictions. Here, we employed a Susceptible-Exposed-Infectious-Recovered-Dead (SEIRD) model to assess SARS-CoV-2 transmission dynamics, working on the number of reported patients in intensive care unit (ICU) and deaths in Sicily (Italy), from 24 February to 13 April. Overall, we obtained a good fit between estimated and reported data, with a small fraction of unreported SARS-CoV-2 cases (19.5%; 95%CI=0%-34.7%) before 10 March lockdown. Interestingly, we estimated that the first set of restrictions reduced transmission rate in the community by 42% (95%CI=38%-46%), and that more stringent measures adopted on 23 March succeeded to drastically curb the transmission rate by 84% (95%CI=80%-88%). Thus, our estimates delineated the characteristics of SARS-CoV2 epidemic before restrictions taking into account unreported data. Further modeling after the adoption of control measures, moreover, indicated that restrictions reduced SARS-CoV2 transmission considerably.

In the midst of the novel coronavirus (SARS-CoV-2) epidemic, examining reported case data could lead to biased speculations and conclusions. Indeed, estimation of unreported infections is crucial for a better understanding of the current emergency in China and in other countries. In this study, we aimed to estimate the unreported number of infections in China prior to 23 March 2020 restrictions. To do that, we developed a Susceptible-Exposed-Infectious-Recovered-Dead (SEIRD) model which estimated unreported cases and infections from the reported number of deaths. Our approach relied on the fact that observed deaths were less likely to be affected by reporting biases than reported infections. Interestingly, we estimated that R0 was 2.43 (95%CI= 2.42 – 2.44) at the beginning of the epidemic, and that 92.9% (95%CI= 92.5% - 93.1%) of total cases were not reported. Similarly, the proportion of unreported new infections by day ranged from 52.1% to 100%, with a total of 91.8% (95%CI= 91.6% - 92.1%) unreported infections. Agreement between our estimates and those from previous studies proved that our approach was reliable to estimate prevalence and incidence of undocumented SARS-CoV2 infections. Once tested on Chinese data, our model could be applied on other countries with different surveillance and testing policies.

Grounded on urban morphology studies, the research tries to overcome the analysis of the permanents elements of the city seeking for a transitional paradigm in urban morphology, aiming at grasping the dynamics in urban evolution and providing operative tools for urban regeneration design in an adaptive approach. A combination of four actions of urban analysis is here suggested to highlight urban dynamics: a. Sorting the transitional steps of urban morphologies (within rapid market processes), b. Underlining rules and Processes characterizing urban coding in transition, c. Mapping urban assemblages in the adaptive city and d. Reading and representing urban permutation phenomenon. The results of this multifaced and multidimensional set of analytical tools allow to outline a new design thinking paradigm moving towards a parametric approach to urban design of cities in transition broadening the extent of urban regeneration process and supporting urban policies in the framework community based approach.

In this study we used a recently developed ex vivo-in vitro model to assess the effect of feeding older adults a casein protein hydrolysate (CPH) compared with non-bioactive non-essential amino acid (NEAA) supplement on Muscle Protein Synthesis (MPS) and Breakdown (MPB). Serum from six healthy older males following overnight fast and 60 min postprandial ingestion of CPH or NEAA (0.33 g.kg^-1 body mass) was used to condition C2C12 myotube media. CPH-fed serum significantly increased MPS compared to fasted serum. In addition, CPH-fed serum induced myotube growth and markedly suppressed atrogin-1, but not MuRF1, expression. Comparatively, no change in MPS, myotube growth and gene expression was observed following NEAA-fed serum treatment. CPH-fed serum from older adults stimulated de novo MPS, suppressed markers of protein breakdown and resulted in myotube growth, indicating a potential role for CPH as a dietary protein source to prevent age-related sarcopenia.

The Individual Work Performance Questionnaire (IWPQ) can be defined as the individual be-haviour capable of generating value and competitive advantage for the organization. It is a mul-ti-dimensional construct, consisting of task performance, contextual performance and counter-productive work behavior. Albeit important, a comprehensive measure of individual job per-formance is still lacking in the Italian context. This paper describes the validation of an Italian adaptation of the IWPQ. A back translation procedure was used. To investigate the psychometric properties of the 18-item Italian IWPQ, 1053 participants (502 men, 47.7%; 551 women, 52.3%) were enrolled; the age of participants ranged between 19 and 69 (Mage=34.6, SD= 11.8), and for the oc-cupation, the sample is classified in blue collar 32.5%, pink collar 33% and white collar 34.5%. Exploratory and confirmatory factor analyses and multigroup confirmatory factor analyses were performed to test the structural factor of the IWPQ. The results supported the goodness of the IWPQ in the Italian context and the scales were found consistent with the original structure. One item was omitted due to a low factor loading, resulting in a final 17-item structure. Multigroup confirmatory factor analysis showed that the factor solution was invariant across both gender and occupational category and found evidence of metric invariance, uniqueness and scalar invariance, and structural invariance. Convergent and discriminant validity were also tested and showed.

Normally, people lose between 50 and 100 hairs a day and generate new ones from the stem cells of hair follicles, but in people suffering from baldness, the condition called alopecia or androgenetic alopecia, the stem cells remain inactive and are unable to regenerate new hair. The stages of hair growth have been studied to better understand how hair grows and what might be done to prevent or treat premature hair loss. Anagen is referred to as the active phase of hair growth in which the hair shaft is produced by the hair follicle, whereas during catagen and telogen phases the lower part of hair follicle regresses until its growth stops. Although 9% of hair follicles remain in telogen at any one time, a variety of factors including growth factors and cytokines promote the transition from telogen to anagen and the subsequent stimulation of hair growth. In this work, we discuss a new possible treatment, AMPLEX PLUS that could help significantly slow hair loss and encourage new hair growth.

The employment of PRP in regenerative medicine has not generated the promised grandiose outcomes. Nonetheless, it currently remains the gold standard strategy for tissue regeneration. Therefore, scientific research has focused on identifying other matrices rich in growth factors and cytokines to improve the efficacy of PRP. In the present study, a new technology called AMPLEX PLUS -compound derived from colostrum enriched with exosomes- was applied in combination with PRP to evaluate the concentration trend of 20 bioactive molecules. The results show that the concentration of all the compounds analyzed increased significantly in PRP samples with AMPLEX PLUS technology compared with samples containing only plasma or PRP, suggesting how this new strategy could improve the performance of PRP and make significant advances in regenerative medicine.

The unresolved territories are privileged places for the proliferation of degradation phenomena that affect the environment and human well-being. The impacts of their critical conditions go beyond the limits of the damaged urban fragments, involving the built environment, society, economy, culture and conditioning quality of life. This paper proposes a methodological approach to landscape design supported by an evaluation framework to orient strategic design planning with specific attention to unresolved territories consistent with circular economy perspective. The circular city principles are applied to spatial planning of landscape, by operationalising Ecosystem Services, Landscape Services, and Ecosystem Disservices, as interpretative categories for multi-dimensional regenerative strategies. Starting from the theoretical framework, the objective of the analysis is to implement an approach to the regenerative design of landscapes of waste, defined wastescapes. The industrial area of East Naples is the case study where an incremental evaluative approach has been defined to design scenarios to provide services and values, aimed to drive the conversion in a regenerativescape. A multi-criteria analysis through PROMETHEE-GAIA method has been implemented to compare the base case scenario with two incremental new scenarios and identify situated sustainable priorities.

In this work we identify combinations of technological activities that signal the presence local capabilities in a country to successfully export a product. We use country-level patent and trade data to generate a multi-layer network, and we apply maximization of entropy to generate synthetic data to effectively divide signal from noise. We show that in several sectors the signal far exceed the noise. Our exercise provides robust evidence of the presence of synergies between technologies to explain trade performances in specific markets. This can be highly useful for policy makers, to inform industrial and innovation policies.

Cardiovascular diseases (CVDs) represent the leading cause of global mortality with 1,7 million deaths a year. One of the alternative systems to drug therapy to minimize the risk of CVDs is represented by alpha-linolenic acid (ALA), an essential fatty acid of the Omega-3 series, known for its cholesterol-lowering effect. The main purpose of this review is to analyze the effects of ALA and investigate the relevant n-6/n-3 ratio in order to maintain functionally beneficial effects. Concerning the lipid-lowering preventive effects, ALA may favorably affect the values of LDL-C and triglycerides in either adult and pediatric populations and it has a positive and protective effect against hypertension, suggesting that ALA is an useful diet-related antihypertensive compound. According to the 2009 EFSA statement, dietary ALA may contribute to reducing the risk of CVDs, thanks to anti-hypertensive, anti-atherosclerotic and cardio-protective effects.

Abstract: Abnormal growth of oligodendrocyte precursor cells (OPCs) importantly contributes to the progression of glioblastoma tumors. Hence, molecules that block OPC growth may be of therapeutic importance in treating gliomas. 2-methoxyestradiol (2ME), an endogenous tubulin interacting metabolite of estradiol is effective against multiple proliferative disorders. Based on its anti-carcinogenic and anti-angiogenic actions it is undergoing phase II clinical trials. We hy-pothesize that 2ME may prevent glioma growth by targeting OPC growth. Here we tested this hypothesis by assessing the impact of 2ME on growth of OPC cell line “Oli-neu” and dissected the underlying mechanism(s). Treatment with 2ME inhibited OPC growth in a concentra-tion-dependent manner and accompanied with significant upregulation in expression of p21 and p27, negative cell cycle regulators. Moreover, treatment with 2ME altered OPC morphology from multi-arm processes to rounded cells. At concentrations of 1uM and greater 2ME induced apoptosis with increased expression of caspase 3, PARP and caspase-7 fragments, externalized phosphatidylserine staining / apopercentage and increased mitochondrial activity. Flow-cytometry and microscopic analysis demonstrated that 2ME triggers endoreduplication in a concentration-dependent fashion. Importantly, 2ME induced cyclin E, JNK1/2 and p53 expres-sion as well as OPC cell fusion, key mechanisms driving endoreduplication or whole-genome duplication. Importantly, inhibition of p53 with pfithrin-α rescued 2ME-induced endoreduplica-tion. The pro-apoptotic and endoreduplication actions of 2ME were accompanied with upregula-tion of survivin, cyclin A, Cyclin B, Cyclin D2, ppRB. Taken together our findings provide evi-dence that 2ME not only inhibits OPC growth and triggers apoptosis, but also activates OPCs in a survival - fight or flight mode leading to endoreduplication. This inherent survival character-istic of OPCs may, in part be responsible for drug resistance in gliomas as observed for many tubulin interacting drugs. Importantly, the fate of OPCs after 2ME treatment may depend on cell-cycle status of the individual cells. Combining tubulin-interfering molecules with drugs, such as pfithrin-α, that inhibit endoreduplication may help inhibit OPC/glioma growth and lim-it drug resistance.

The detection and enrichment of circulating melanoma cells is a challenge as the cells are very heterogeneous in terms of their biomechanical properties and surface markers. In addition, there is a lack of valid and reliable biomarkers that predict progress and therapeutic response. We here analyzed the elasticity of A375 melanoma cells applying force spectroscopy and a microfluidic method. To identify and eventually separate circulating tumor cells, it is crucial to precisely know their physical properties. First, we used standard AFM force spectroscopy, where the elasticity of the cells is calculated from indentation with a pyramidal tip. To extend the limits of measurement with a tip, we then used cantilevers without a tip to press on the cells over a large area. The resulting Young’s moduli are slightly lower and vary less without tip presumably because of the inhomogeneity of the cells. Finally, we implemented our microfluidic method. We measured single cell elasticity by analyzing its deformation in high-speed micrographs while passing a stenosis. Combining the force field and the change in shape provides the basis for a stress strain diagram. The results from microfluidic deformation analysis were in accordance with the results from force spectroscopy. The microfluidic method provides advantages over conventional methods, since it is less invasive and less likely to harm the cell during the measurement, and the whole cell is measured as one entity without contact to a stiff substrate, while force spectroscopy is limited to the contact area of the tip, and in some cases dependent of the cell substrate interaction. Consequently, microfluidic deformation analysis allows to predict the overall elastic behavior of the whole inhomogeneous cell in three-dimensional force fields. This method may contribute to improve the detection of circulation melanoma cells in the clinical practice.

This paper presents a modular approach to generic exergame design that combines custom physical exercises in a meaningful and motivating story. This aims to provide a tool that can be individually tailored and adapted to people with different needs, making it applicable to different diseases and states of disease. The game is based on motion capturing and integrates four example exercises that can be configured via our therapeutic web platform "Blexer-med". To prove the feasibility for a wide range of different users, evaluation tests were performed on 14 patients with various types and degrees of neuromuscular disorders, classified into three groups based on strength and autonomy. Users were free to choose their schedule and frequency. Game scores and three surveys (before, during, and after the intervention) showed similar experiences for all groups, with the most vulnerable having the most fun and satisfaction. The players were motivated by the story and by achieving high scores. The average usage time was 2.5 times per week, 20 minutes per session. Pure exercise time was about half the game time. The concept has proven feasible and forms a reasonable basis for further developments. The full 3D exercise needs further fine-tuning to enhance fun and motivation.

The Coronavirus Disease 2019 (COVID-19) is a new viral infection caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2). Genomic analyses have revealed that SARS-CoV-2 is related to Pangolin and Bat coronaviruses. In this report, a structural comparison between the Sars-CoV-2 Envelope and Membrane proteins from different human isolates with homologous proteins from closely related viruses is described. The analyses here reported show the high structural similarity of Envelope and Membrane proteins to the counterparts from Pangolin and Bat coronavirus isolates. However, the comparisons have also highlighted structural differences specific of Sars-CoV-2 proteins which may be correlated to the cross-species transmission and/or to the properties of the virus. Structural modelling has been applied to map the variant sites onto the predicted three-dimensional structure of the Envelope and Membrane proteins.

Specific foods and nutrients help prevent the progression from persistent high-risk human papillomavirus (hrHPV) infection to cervical cancer (CC). We aimed to focus on dietary patterns which may be associated with hrHPV status and risk of high-grade cervical intraepithelial neoplasia (CIN2+). Overall, 539 eligible women, including 127 CIN2+, were enrolled in a cross-sectional study, and tested for hrHPV infection. Food intakes were estimated using a food frequency questionnaire. Logistic regression models were applied. Using the Mediterranean Diet Score, we demonstrated that, among 252 women with normal cervical epithelium, medium adherence to Mediterranean diet decreased odds of hrHPV infection when compared to low adherence (adjOR=0.40, 95%CI=0.22-0.73). Using principle component analysis, we also identified two dietary patterns which explained 14.31% of variance. Women in the 3^rd and 4^th quartiles of the “western pattern” had higher odds of hrHPV infection when compared with 1^st quartile (adjOR=1.77, 95%CI=1.04-3.54 and adjOR=1.97, 95%CI=1.14-4.18, respectively). Adjusting for hrHPV status and age, women in the 3^rd quartile of the “prudent pattern” had lower odds of CIN2+ when compared with 1^st quartile (OR=0.50, 95%CI=0.26-0.98). Our study is the first to demonstrate the association of dietary patterns with hrHPV infection and CC, discouraging unhealthy habits in favour of Mediterranean-like diet.

Anthracnose stands as the primary obstacle to lupin cultivation, impeding development despite the considerable agronomic, ecological, and economic potential of such legume crops. This review explores recent efforts to unravel the complexities of anthracnose in domesticated lupins, focusing on both the plant perspective and the causative pathogenic agent, Colletotrichum lupini. Leveraging cutting-edge technologies has yielded crucial insights into various facets of this devastating disease, encompassing plant and pathogen biology, genetic and molecular regulations of the interaction, fungal diversity and population dynamics, and screening of plant genetic resources for anthracnose resistance. The lack of effective disease control measures, relying primarily on the use of disease-free seeds, highlights the need to develop anthracnose-resistant varieties. However, challenges arise from the intricacy of lupin's response to the disease, influenced by polygenic inheritance, in spite of loci with major effects, and environmental factors. The slow pace of genetic improvement underscores the need for more efficient breeding processes, including biotechnological approaches. This review offers a comprehensive overview of current progress and knowledge gaps, stressing the urgent need to further enhance understanding of C. lupini pathogenic mechanisms and lupin‘s resistance. Integrating advanced technologies and accelerated research efforts is paramount for achieving efficient disease management and sustainable lupin cultivation in the face of anthracnose challenges.

Epithelial surfaces in humans are home to symbiotic microbes (i.e., microbiota) that influence the defensive function against pathogens depending on the health of the microbiota. Healthy microbiota contribute to the well-being of their host in general (e.g., via the gut-brain-axis), and their respective anatomical site in particular (e.g., oral, urogenital, skin or respiratory microbiota). Despite efforts towards a more responsible use of antibiotics, they are often prescribed for uncomplicated, self-limiting infections and can have a substantial negative impact on the gut microbiota. Treatment alternatives such as non-steroidal anti-inflammatory drugs may also influence the microbiota and thus can have lasting adverse effects. Herbal drugs offer a generally safe treatment option for uncomplicated infections of the urinary or respiratory tract. Additionally, their microbiota preserving properties allow for a more appropriate therapy of uncomplicated infections without contributing to an increase in antibiotic resistance or disturbing the gut microbiota. Here, herbal treatments may be a more appropriate therapy with a generally favorable safety profile.

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.

Cutaneous Melanoma (CM) is the most lethal form of skin cancer if it becomes metastatic, where treatment options and survival chances decrease dramatically. Immunotherapy treatments based on the immunologic checkpoint inhibitors (PD-1 and CTLA4) constituted a main breakthrough in the treatment of metastatic CM, particularly in the long-term benefit. However, several molecular pathways are responsible for the failure of this strategy in about 50-70% of CM patients. Some Long Non-coding RNAs (lncRNAs), and circular RNAs (circRNA) are implicated in triggering pro- and antitumorigenic responses to various cancer treatments. The relationship between lncRNA, circRNA and Immune Checkpoint Blockade (ICB) immunotherapy is not extensively explored in cutaneous metastatic melanoma (CMM). The aim of this study is to evaluate the potential role of both circRNA and lncRNA as a predictive immunotherapy biomarker in CMM. RNA-seq from 12 FFPE samples from the metastatic biopsy of metastatic melanoma patients treated with Nivolumab were analyzed. Our findings indicate that specific lncRNA and circRNA are involved in regulatory networks of the immune response against metastatic melanoma under treatment with nivolumab. Moreover, we have established a risk score that allows the prediction of Overall survival (OS) and Progression-free survival (PFS) of CMM patients with high accuracy. This proof of principle work provides a possible insight on the function of ceRNA, contributing to decipher the complex molecular mechanism of ICB cancer treatment response.

Given that metabolic syndrome, along with obesity as one of its key components, remains one of the leading yet insufficiently addressed public health issues, what contributes to the development and maintenance of the disorder must certainly attract the attention of professionals and scientists. Precisely because of this phenomenon, eating patterns associated with metabolic syndrome should be studied and attempts should be made to uncover patterns in occurrence. The aim of this study is to review the literature and consider the connection between metabolic syndrome and eating patterns such as emotional and compulsive eating, as well as through the lens of food addiction. Furthermore, we have attempted to uncover the role of psychiatry and psychotherapy in the treatment of metabolic syndrome and delve into the complexity of recognizing these patterns and emphasize the importance of a multidisciplinary approach in the treatment of metabolic syndrome.

In systems biology, biological phenomena are often modeled by ODE and distributed in the de facto standard file format SBML. The primary analyses performed with such models are dynamic simulation, steady-state analysis, and parameter estimation. These methodologies are mathematically formalized, and libraries for such analyses have been published. Several tools exist to create, simulate, or visualize models encoded in SBML. However, setting up and establishing analysis environments is a crucial hurdle for non-modelers. Therefore, easy access to perform fundamental analyses of ODE models is a significant challenge. We developed SBMLWebApp, a web-based service to execute SBML-based simulations, steady-state analysis, and parameter estimation directly in the browser without the need for any setup or prior knowledge to address this issue. SBMLWebApp visualizes the result and numerical table of each analysis and provides a download of the results. SBMLWebApp allows users to select and analyze SBML models directly from the BioModels Database. Taken together, SBMLWebApp provides barrier-free access to an SBML analysis environment for simulation, steady-state analysis, and parameter estimation for SBML models. SBMLWebApp is implemented in Java™ based on an Apache Tomcat® web server using COPASI, the SBSCL, and LibSBMLSim as simulation engines. SBMLWebApp is licensed under MIT with source code available from https://github.com/TakahiroYamada/SBMLWebApp. The program runs online at http://simulate-biology.org.

Introduction: Substance-induced psychotic disorder (SIPD) is a mental health condition linked to the use of a psychotropic substance whose pathogenesis has not been totally clarified. The present retrospective observational study has the objective to identify differences in clinical features and peripheral biomarkers in SIPD patients according to the main substance of abuse.Methods: A total sample of 218 patients was divided in 3 groups according to the type of consumed substance: alcohol, cannabis and psychostimulants. The 3 groups were compared for continuous variables by one-way analyses of variance (ANOVAs) and for qualitative variables by χ² tests. After removing alcohol-induced psychotic disorder group, the same analyses were repeated. Statistically significant variables from these latter analyses were included in a binary logistic regression model to confirm their reliability as predictors for cannabis- or psychostimulants-induced psychotic disorders. Results: Psychotic cannabis abusers were younger (p<0.01) and had an earlier age at onset (p<0.01). On the contrary, alcohol consumers resulted to have a longer duration of illness (p<0.01), more previous hospitalizations (p=0.04), more frequent medical comorbidity (p<0.01), higher mean Modified Sad Person Scale scores (p<0.01). Finally, psychostimulant abusers had more frequently a lifetime history of poly-substance use disorders (p<0.01). Binary logistic regression revealed that higher mean Brief Psychiatric Rating Scale scores (p<0.01) higher sodium (p=0.012) and haemoglobin(p=0.040) plasma levels were predictors of cannabis misuse in SIPD patients.Conclusions: Different clinical factors and biochemical parameters con be associated to SIPD according to the main substance of abuse, thus requiring a specific management by clinicians.

Background: Both natural immunity and vaccine-induced immunity to COVID-19 may be useful to reduce the mortality/morbidity of this disease, but still a lot of controversy exists. Aims: This narrative review analyzes the literature about: a) the duration of natural immunity; b) cellular immunity; c) cross-reactivity; d) the duration of post-vaccination immune protection; e) the probability of reinfection and its clinical manifestations in the recovered patients; f) comparisons between vaccinated and unvaccinated in the possible reinfections; g) the role of hybrid immunity; h) the effectiveness of natural and vaccine-induced immunity against Omicron variant; i) comparative incidence of adverse effects after vaccination in recovered individuals vs. COVID-19-naïve subjects. Material and Methods: through multiple search engines we investigated COVID-19 literature related to the aims of the review, published since April 2020 through July 2022, including also the previous articles pertinent to the investigated topics. Results: nearly 900 studies were collected and 238 pertinent articles were included. It was highlighted that the vast majority of individuals after COVID-19 develop a natural immunity both of cell-mediated and humoral type, which is effective over time and provides protection against both reinfection and serious illness. Vaccine-induced immunity was shown to decay faster than natural immunity. In general, the severity of the symptoms of reinfection is significantly lower than in the primary infection, with a lower degree of hospitalizations (0.06%) and an extremely low mortality. Conclusions: this narrative review regarding a vast number of articles highlighted the valuable protection induced by the natural immunity after COVID-19, which seems comparable or superior to the one induced by anti-SARS-CoV-2 vaccination. Vaccination of the unvaccinated COVID-19-recovered subjects may not be indicated. Further research is needed in order to: a) measure the durability of immunity over time; b) evaluate both the impacts of Omicron-5 on vaccinated and healed subjects and of hybrid immunity.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease with high prevalence worldwide, including countries from Asia, Africa and Latin America, and in different ethnic groups. In recent years, more attention on AD heterogeneity associated on multiple factors, including patient’s ethnic background, has been posed, resulting in an increasing body of clinical, genetic, epidemiologic, and immune-phenotypic evidence that delineate differences among racial groups with AD. Filaggrin (FLG) mutations, the strongest genetic risk factor for the development of AD, are detected in up to 50% of European and 27% of Asian AD patients, while very rarely in Africans. The Th2 activation is a common attribute of all ethnic groups, though the Asian endotype of AD is also characterized by an increased Th17-mediated signal whereas African Americans own a strong Th2/Th22 signature and the absence of Th1/Th17 skewing. In addition, the ethnic heterogeneity may own important therapeutic implications as the genetic predisposition may affect treatment response and, thereby, a tailored strategy that better targets the dominant immunologic pathways in each ethnic subgroup may be envisaged. Nevertheless, white patients with AD represent the largest ethnicity enrolled and tested in clinical trials and the most treated in a real-world setting, limiting the investigation about safety and efficacy across different ethnicities. The purpose of this review is to describe the heterogeneity of pathophysiology across ethnicities and its potential therapeutic implications.

: Nonylphenol is an endocrine disruptor who belongs to alkylphenol group of chemicals and its high occurrence in the environment can caused an adverse effect on human health. The breast milk can serve as a marker to take measure of human exposure to these chemicals through different routes of exposure. In this study, the influence of different factors (kind of wastes mothers drink, consummation of fish, pork and beef; using gloves, mail polish, using vitamins and medication) on the concentration on nonylphenol in breast milk were studied. Concentrations of nonylphenol in breast milk were determined by high-performance liquid chromatography (HPLC) with fluorescence detection. The lowest and highest concentration of nonylphenol in breast milk was 0.97 ng/mL and 4.37 ng/mL, respectively. The selected factors such as pork, beef, fish consumption, vitamin supplementation, medication, using of gloves, nail polish and gel nails were observed in relation to 4-nonylphenol concentration.

As a result of climate change, the Mediterranean Sea has been exposed to an increase in frequency and intensity of marine heat waves in the last decades, some of which caused mass mortality events of benthic invertebrates, including sponges. Sponges are an important component of benthic ecosystems and can be the dominant group in some rocky shallow-water areas in the Mediterranean Sea. In this study, we exposed the common shallow-water Mediterranean sponge Chondrilla nucula (Demospongiae: Chondrillidae) to six different temperatures for 24 h, ranging from temperatures experienced in the field during the year (15, 19, 22, 26, 28 °C) and above normal temperatures (32 °C) and metabolic (respiration rate) and behavioural (clearance rate) were measured. Both respiration and clearance rates were affected by temperature. Respiration rates increased at higher temperatures but were similar between 26 and 32 °C treatments. Clearance rates decreased at temperatures > 26 °C, indicating a drop in food intake that was not reflected by respiration rates. This decline in feeding, while maintaining high respiration rates, may indicate a negative energy balance that could affect this species under chronic or repeated thermal stress exposure. C. nucula will probably be a vulnerable species under climate change conditions, affecting its metabolic performance, ecological functioning and the ecosystem services it provides.

The effects of the climate crisis are affecting ecosystems at different scales and magnitudes. This paper focuses on a massive Mediterranean mussel die-off observed along the middle Italian Adriatic coast in the summer of 2022. We considered the possible environmental causes of this phenomenon and carried out a climatic analysis of the last decade. We performed field surveys in different locations along a 16 Km coastal stretch (from Martinsicuro (TE) on the South, to Grottammare (AP) on the North). The study area includes two marine Sites of Community Importance under the European Natura 2000 network. The mussels die-off has interested practically all the natural mussel-beds colonizing the study area. Mussels are sessile filter-feeding organisms inhabiting the intertidal zone, therefore, are highly exposed to variations in environmental conditions such as temperature and nutrient load. We discuss the possible causes of this die-off, proposing that high temperature and the scarce availability of food acted simultaneously as stress factors, generating local unsustainable living conditions for this species.

The enteric nervous system (ENS) is a neural network referred to as "the brain in the gut" because of its similarities to the central nervous system (CNS). The ENS consists of numerous types of neurons and glial cells distributed in two intramuscular plexuses that span the length of the intestine and control coordinated smooth muscle contractile activity and other intestinal functions. It is well-established that reciprocal communication exists between the brain and the gastrointestinal tract. Although the ENS can function independently, it is connected to the CNS through the afferent and efferent pathways of the parasympathetic and sympathetic nervous systems. In addition to regulating ENS function by the CNS, these connections are likely to be critically involved in the pathophysiology of Parkinson's disease (PD). PD is a common neurodegenerative disorder that presents with non-motor and motor symptoms. Surprisingly, ENS lesions have been shown to occur very early in the disease, even before CNS involvement. This has led to the postulation that the ENS may be central to the pathophysiology of PD. Autopsy studies have shown that α-synuclein (αS) aggregates in PD patients are found both in the substantia nigra (SN) and the ENS. Therefore, it has been hypothesized that the pathological process leading to PD may initially occur in the ENS years before the appearance of motor features. This process induces misfolding and aggregation of αS in specific subtypes of neurons in the CNS. Finally, it spreads retrogradely in the CNS through preganglionic vagal fibers to the dorsal motor nucleus of this nerve and to other central nervous structures. In addition to the presumed role in the spread of the disease process, it has also been suggested that pathological changes in the ENS might be involved in the gastrointestinal dysfunction frequently seen in Pd patients. Starting from the evidence in animal models and using a translational point of view, in this review, we aim to summarize the role of the ENS in the pathogenesis of PD and how this system could be modulated for a novel therapeutic approach. While acknowledging the presumed role of the microbiome in the gut-brain axis, we will shift the focus from this point of view to focus more on the neurons of the ENS.

Background: Fertility is a crucial component of population maintenance and growth. A declin-ing fertility trend has been observed over the past two decades, and it continues. Objective: The aim of this research was to examine the level of fertility knowledge, factors in-fluencing fertility knowledge, and the relationship between fertility knowledge and the decision to have a child. Methods: A cross-sectional study was conducted on a sample of mothers in five hospitals on the Adriatic coast of the Republic of Croatia, involving 1541 mothers from September 2021 to De-cember 2023. The Cardiff Fertility Knowledge Scale was used for the research. Results: The participants were divided into two groups based on fertility status in women, spe-cifically the period of declining fertility in women. Group 1 included participants aged 18-31 with sustained fertility, and Group 2 included participants aged 32 and older experiencing de-clining fertility. Fertility knowledge was 58.9%. Women with higher educational status showed better results (62.3%). The most common sources of fertility knowledge were the healthcare sys-tem and the internet. Factors associated with the level of fertility knowledge included higher education, marital status, and higher economic status. Conclusion: The research results reveal a lack of fertility knowledge among participants, as well as an intention to have a child in later stages of life. The lack of formal education on this topic leads to information gathering from unreliable sources.

The present clinical study was approved by the Review Board for Animals Care of the University of Parma prot N. 03/CESA /2023, which provided a consent to the clinical study: regulation (EU) no. 536/2014. (22A01712) (GU General Series n.65 of 18-03-2022); European Law (O.J. of E.C. L 358/1 12/18/1986), and USA Laws (Animal Welfare Assurance No A5594-01, Department of Health and Human Services, USA). The owners signed a voluntary informed consent form prior to the dogs’ enrollment in the study. Twenty female dogs, aged 1±1.5 months, and weighing 16± 0.5 kg were enrolled in the study. The inclusion criterion of the patients was to undergo ovariectomy surgery; dogs enrolled in this study had normal physiological, haematological and biochemical parameters.

Plant cells are omnipotent and breeding of new varieties can be achieved by protoplast fusion. Such fusions can be achieved by treatment with poly(ethylene glycol) or by applying an electric field. Microfluidic devices allow for controlled conditions and targeted manipulation of small batches of cells down to single cell analysis. To provide controlled conditions for protoplast fusions and achieve high reproducibility, we developed and characterized a microfluidic device to reliably trap few of Arabidopsis thaliana protoplasts and induced a cell fusion by controlled addition of poly(ethylene glycol) (PEG, with a molecular weight of 6000). Experiments were conducted to determine the survival rate of isolated protoplasts in our microfluidic system. Afterwards, PEG induced fusion was studied. Our results indicate that the following fusion parameters had significant impact on the fusion efficiency and duration: PEG concentration, osmolarity of solution, and flow velocity. PEG concentration below 10% led to only partial fusion. Osmolarity of the PEG fusion solution was found to strongly impact the fusion process; complete fusion of two source cells sufficiently took part in slightly hyper osmotic solutions, whereas iso-osmotic solutions led to only partial fusion at 20% PEG concentration. We observed accelerated fusion for higher fluid velocities. Up to this study, it was common sense that fusion is one directional, i.e. once two cells were fused into one cell they stay fused. Here, we present for the first time reversible fusion of protoplasts. Our microfluidic device paves the way to a deeper understanding on the kinetics and processes of cell fusion.

In recent years, the interest in increasingly sustainable agriculture has also turned attention towards new crops which could enter the food chain as new protein and oil sources or that can be used as new cover crops. In this scenario, Camelina sativa is a perfect crop to study. Camelina is an annual herbaceous plant belonging to the Brassicaceae which is interesting for its oil content, since the seeds contain about 40% of oils, with a high level of polyunsaturated fatty acids (30-40% alpha linolenic acid, 15-25 % linoleic acid, 15% oleic acid and about 15% eicosenoic acid). It is a hexaploid species (2n = 40, genome size ~782 Mb) characterized by rapid growth, short life cycle (85-100 days for spring varieties, 190-210 for autumn varieties) and low input cultivation needs. All these traits make it suitable for use in marginal areas. However, its use in feed and food is limited by the presence of glucosinolates (GLS). GLS are sulfur molecules involved in plant defense. In recent years, they have been studied not only as anti-nutritionals, but also for their anti-carcinogenic effects against chronic inflammatory and heart diseases and for their use as natural pesticides. Given the recent interest in camelina and its highly nutritious oil, eight pure lines and a synthetic population were compared in two different growing periods, spring and winter. In this work, the genetic materials were characterized for different phenotypic traits, yields and yield components, bromatological and glucosinolate content. The results confirmed that in North Italy camelina has higher yields if cultivated in the autumn-winter period (about 2 t/ha vs 0.6 t/ha), furthermore, a negative correlation was found between spring and winter yields, indicating that varieties that produce more in winter cultivation produce less in spring cultivation. Moreover, to our knowledge, it is the first work in which a synthetic population of Camelina sativa has been tested and proved to be a valid solution for use in various environments both for its adaptability and for the low content of glucosinolates (about 17 mmol/ kg).

This study explores the perspectives and practices of architects regarding the reuse of wood in construction across five South-Central European countries: Slovenia, Serbia, North Macedonia, Bosnia and Herzegovina (BiH), and Montenegro. Based on a survey of architectural professionals, the research explores their attitudes, challenges, and motivations for using reclaimed wood, with a focus on circular construction principles. Key findings reveal unanimous agreement among re-spondents that both their profession and government entities inadequately support or promote wood reuse within the context of circular construction. While architects value reclaimed wood, there are country-specific variations. Environmental benefits, unique aesthetics, historical value, and sustainability are cited as primary motivators for reclaimed wood use. Additionally, re-spondents emphasize the ecological aspect as the most important consideration in wood product reuse, followed by economic and technological factors. Common concerns revolve around the long-term quality and maintenance of wood products. This research provides insights into the challenges and opportunities surrounding reclaimed wood use in South-Central Europe, high-lighting the need for support mechanisms and increased awareness to advance circular construc-tion practices in the region. These findings can have implications for architects and investors by identifying market opportunities, promoting eco-friendly practices, and providing valuable in-sights for future building designs with a focus on reclaimed wood elements within circular con-struction.

Background Most of the Leber hereditary optic neuropathy (LHON) cases are bilateral and sequential, how-ever there are rare unilateral examples, or those in which the delay of onset of vision loss between one and the other eye is longer. In the case of presumed childhood amblyopia in one eye, the vision loss in the good eye may be the only symptom of bilateral disease, that was unnoticed in previ-ously amblyopic eye, or a preexisting episode of LHON on the “amblyopic” eye. Clinical decision in such cases may be difficult and suggestive for other forms of atypical optic neuropathy until confirmed by genetic testing. Case series We present three genetically confirmed (MT-ND1:m.3700G>A, MT-ND6:m14484 T>C, and MT-ND4:m.11778G>A) patients with subacute vision loss in previously good eye with the other eye believed to be amblyopic from the childhood, and their features different of what would be expected in true amblyopia. In all, electrophysiology testing showed bilaterally reduced ampli-tude of PERG with low VEP P100 wave amplitudes and prolonged peak time in both eyes, also unusual for amblyopia. During the follow-up, pallor of the optic discs progressed in all eyes. Significant thinning of the retinal nerve fiber layer around the optic disc (pRNFL) and ganglion cell complex (GCC) in the macular region was present. All three patients had peculiar history. First patient was treated for presumed hyperopic amblyopia that did not improve since child-hood and experienced visual loss on the good eye at the age of 17 and was negative for the three typical LHON mutations. Extended testing confirmed atypical pathogenic variant MT-ND1:m.3700G>A in homoplasmy. The second patient with presumed strabismic amblyopia had unusual presentation of vision loss only at the age of 61 and after exclusion of other causes, typical MT-ND4:m.11778G>A pathogenic variant was found in homoplasmy. The third case was peculiar as he had presumed strabismic amblyopia since childhood and had some degree of disc pallor in the amblyopic eye upon presenting with loss of vision on the good eye at the age of 21 and typical pathogenic variant m14484 T>C, p.Met64Val was subsequently confirmed. However, one year after the disease onset, he started to experience significant spontaneous functional im-provement in the non-amblyopic up to 1.0 Snellen, whilst improvement in the presumed amblyop-ic eye was modest, suggesting preexisting amblyopia. This interestingly extensive improvement was carefully followed by electrophysiology as well as visual acuity and fields. Conclusion This report shows three different scenarios of presentation of LHON in patients with presumed uniocular amblyopia from childhood. In such cases, the diagnosis may be difficult and detailed structural and functional evaluation of the optic nerve head is necessary to assess whether earlier LHON episode was misdiagnosed as amblyopia or whether LHON presented bilaterally on both eyes whilst only being noticed in the previously good eye.

Activated Corrosion Products (ACPs) formation and deposition pose a critical safety issue for nuclear fusion reactors. The working fluid transports the ACPs towards regions accessible to worker personnel. Predicting ACPs formation deposition and transport is fundamental for source term identification, reduction of radiation exposure assessment, maintenance plan definition, design optimization, and waste management. The code OSCAR-Fusion has been developed by the CEA (France) to evaluate the ACPs generation and transport in closed water-cooled loops for fusion application. This work aims at assessing the impact of water chemistry on the transport, precipitation, and deposition of corrosion products for the EU-DEMO divertor Plasma Facing Unit Primary Heat Transfer System. Sensitivity analyses and uncertainty quantification are needed due to the multi-physics phenomena involved in ACPs formation and transport. The OSCAR-Fusion/RAVEN code coupling developed by the Sapienza University of Rome and ENEA has been used. This work presents the perturbation results of different parameters chosen for a closed water-cooled loop considering a continuous scenario of 1888 days. The aim of this work is to assess the variation of build-up of ACPs, perturbing the alkalizing agent concentration into the coolant and the corrosion and release rates of different materials.

Background: This study aimed to investigate the association between the internal derangement of the temporomandibular joint (TMJ), in particular the severity of disc displacement (DD), and the presence of generalized joint hypermobility (GJH) in growing patients evaluated on magnetic resonance images (MRI). The study also investigated the relationship between the stages of DD severity and age. Methods: This cross-sectional study has been conducted on a pre-orthodontic population (8-16 years). The GJH was assessed with the Beighton test (cutoff ≥ 4) and the final sample of 56 patients was divided into two groups: a Study Group, 30 subjects with GJH, and a Control Group, 26 subjects without GJH. The disc position was evaluated on MRI and the severity of DD was classified in four stages. Pearson's χ2 Test was performed for the analysis of the statistical correlation. Results: A statistically significant relationship between GJH and disc position was found, in particular a disc displacement with reduction (DDwR) and DD severity. It also emerged a positive association between the severity of DD and age, that increased with increasing age. Conclusions: Growing patients with GJH have a higher risk of developing DD and with more severe stages. The risk of developing DD and the severity increases with increasing age.

The COVID-19 pandemic made it harder to communicate accurate information about vaccines because of the spread of misinformation. The European Medicines Agency (EMA) tried to reas-sure the public by communicating about the development and approval of COVID-19 vaccines. They surveyed patients/consumers, healthcare professional organizations, and individual stake-holders to see if their core information materials were informative and well understood. They also asked about the public's preferred communication channels. The surveys showed that indi-vidual patients/consumers generally prefer to get information about COVID-19 vaccines from the internet or mass media. Organizations and individual healthcare professionals prefer to get in-formation from national and international health authorities' sources. This supports EMA's ap-proach of using media, stakeholder engagement, and web-based formats to communicate about COVID-19 vaccines. Both at the EU and local levels, participants had a good understanding of the key messages from regulators and found the materials useful and relevant. However, some im-provements were recommended to the visuals, texts, and dissemination formats. These recom-mendations were generally consistent in both contexts. User-testing of proactive communication materials aimed at prebunking misinformation during a public health crisis helps to ensure that users understand the development and safety safeguards of novel vaccine technologies. This in-formation can then be used as a basis for evidence-based communication activities by regulators and public health bodies in an emergency context.

MicroRNAs are small non-coding RNAs, which contribute to the regulation of many physiolog-ical and pathological processes. Conventionally, miRNAs perform their activity in the cyto-plasm, where they regulate gene expression by interacting in a sequence-specific manner with mature messenger RNAs. Recent studies point to the presence of mature miRNAs in the nucleus. This review summarizes current findings regarding the molecular activities of nuclear miRNAs. These molecules can regulate gene expression at the transcriptional level by directly binding DNA on the promoter or the enhancer of regulated genes. MiRNAs recruit to these regions dif-ferent protein complexes, resulting both in activation or repression of transcription, through a number of molecular mechanisms. Haematopoiesis is presented as a paradigmatic biological process whereby nuclear miRNAs possess a relevant regulatory role. Nuclear miRNAs may af-fect gene expression also acting on nuclear mRNA processing and on the biogenesis of miRNA themselves by regulating pri-miRNA maturation. Overall, nuclear miRNAs are biologically ac-tive molecules that can be critical for the fine tuning of gene expression and deserve further studies in a number of physiological and pathological conditions

Gelatin fibers have a specific surface and high porosity, which is why their use in medicine and the food industry is being researched. This article explores the potential of centrifugal spinning to produce gelatin fibers. Gelatin for fiber preparation is obtained from a non-traditional source of collagen (chicken by-products) using a unique enzymatic process. The fiber quality is compared with those prepared from traditional collagen tissues (porcine, bovine). The results show that fibers crosslinked with glutaraldehyde vapor preserve their structure even in contact with water. Using a cross-linker controls swelling ability and solubility while maintaining the fiber structure. On the contrary, uncross-linked gelatin fibers are water soluble due to a high surface-to-volume ratio, facilitating water penetration and dissolution. Scanning electron microscopy (SEM) provided a clearer picture of the morphology of gelatin fibers obtained by centrifugal spinning. Differences in the amount of bonding depending on the raw material used and the presence of cross-linker were analyzed using Fourier transform infrared spectroscopy (FTIR). The overall results showed that chicken gelatin is a suitable alternative to gelatins from traditional sources.

The adipose-derived mesenchymal stem cells are becoming the tool of choice for many clinical applications and nowadays, nearly 200 clinical trials are running worldwide to prove the efficacy of this cell type for many diseases and pathological conditions. To reach the goal of cell therapies and produce ATMPs as drugs for regenerative medicine, it is necessary to properly standardize the GMP processes and thus collection methods, transportation strategies, extraction protocols and characterization procedures without forgetting that all the tissues of the human body are characterized by a wide inter-individual variability genetically determined and acquired during life. Here we compare 302 samples processed under GMP rules to exclude the influence of the operator and of the anatomical site of collection. Variability in the age of patients, gender and laboratory parameters like total cell number, cell viability, stem cell number and other stromal vascular fraction cell sub-populations have been compared to each other. Results show that, when the laboratory protocol is standardized, the variability in quantifiable cell parameters is widely statistically non-significant, meaning that we can make a further step toward standardized advanced cell therapy products.

In recent years, the need to contain healthcare costs due to the growing public debt of many countries, combined with the need to reduce costly travel by patients unable to move autonomously, have captured the attention of public administrators towards tele-rehabilitation. This trend has been consolidated overwhelmingly following the Covid-19 pandemic, which has made it precarious, difficult and even dangerous for patients to access hospital facilities. We present a platform devoted to the rapid prototyping of Virtual Reality based, cognitive tele-rehabilitation exercises. Patients who experienced injury or pathology need to practice a continuous training in order to recover functional abilities, and the therapist need to monitor the outcomes of such practices. The Virtual Reality exercises are designed on Unity 3D to empower the therapist to set up personalised exercises in a easy way, enabling the patient to receive personalized stimuli, which are crucial for a positive outcome of the practice. Furthermore, the reaction speed of the system is of fundamental importance, as the temporal evolution of the scene must proceed parallel to the patient’s movements, to ensure an effective and efficient therapeutic response. So, we optimized the Virtual Reality application in order to make the loading phase and the startup phase as fast as possible and we have tested the results obtained with many devices: in particular computers and smartphones with different operating systems and hardware. The implemented platform integrates in Nu!Reha system®, a tele-rehabilitation set of services that helps patients to recover cognitive and functional capabilities.

We review and refine the geological setting of an area located nearby the Tyrrhenian seacoast, in the inner zone of the Northern Apennines (southern Tuscany), where a Neogene monzogranite body (estimated in about 3 km long, 1.5 km wide, and 0.7 km thick) emplaced during early Pliocene. This magmatic intrusion, known as the Gavorrano pluton, is partially exposed in a ridge bounded by regional faults delimiting broad structural depressions. A widespread circulation of geothermal fluids accompanied the cooling of the magmatic body and gave rise to an extensive Fe-ore deposit (mainly pyrite) exploited during the past century. The tectonic setting which favoured the emplacement and exhumation of the Gavorrano pluton is strongly debated with fallouts on the comprehension of the Neogene evolution of this sector of the inner Northern Apennines. Data from a new fieldwork dataset, integrated with information from the mining activity, have been integrated to refine the geological setting of the whole crustal sector where the Gavorrano monzogranite was emplaced and exhumed. Our review, implemented by new palynological, petrological and structural data pointed out that: i) the age of the Palaeozoic phyllite (hosting rocks) is middle-late Permian, thus resulting younger than previously described (i.e. pre-Carboniferous); ii) the P-T conditions at which the metamorphic aureole developed are estimated at about 660 °C and at a maximum depth of c. 5 km; iii) the tectonic evolution which determined the emplacement and exhumation of the monzogranite is constrained in a transfer zone, in the frame of the extensional tectonics affecting the area continuously since Miocene.

Durum wheat is an important staple food used to obtain several products. At first the wheat is milled to obtain different products: bran, semolina and flour. These products are the base of several artifacts with varying properties both from a nutritional point of view and flavoring characteristics. It is known that most elements concentrate in the outer layers of the wheat seed (pericarp and aleurone) so that the content of the elements vary a lot in the ground products. The present study investigates the characterizing elements of the milled products and the effect of cultivation protocol applied. We measured, by ICP-OES, the concentration of 28 elements in the whole seed and in any grinding products; the results show that only few elements characterize each product. Few elements, but different for each product, permit to disclose the kind of agri-cultural method used: organic or conventional protocol. Five elements: B, Cd, Cu, K, Se, are the most important to distinguish between organic and conventional agriculture by PCA and PLS analysis; these elements also permit some differentiation of products.

Traumatic brain injury (TBI) affects millions of people each year. Previous studies using the central fluid percussion injury (CFPI) model in adult male rats indicated that elevated intracranial pressure (ICP) was associated with long-term effects, including neuronal cell loss and increased sensory sensitivity post-injury and secondary ICP elevation, that were not seen following injury alone. Investigations also indicated that Cathepsin B (Cath B), a lysosomal cysteine protease, may play a role in the pathological progression of neuronal membrane disruption; however, the specific impact of Cath B inhibition following CFPI remains unknown. Thus, the focus of this study was to evaluate the effects of Cath B inhibition via intracerebroventricular infusion of CA-074Me 2w following injury with or without secondary elevation of ICP. This was accomplished using adult male rats continuously infused with CA-074Me or 10% DMSO as a vehicle control for 2w following either sham injury, a CFPI only, or a CFPI with subsequent ICP elevation to 20mmHg. We assessed Cath B activity in the lateral neocortices and liver, evaluated protein levels of Cath B and Cath B binding partners AIF, Bcl-XL, and Bak. We also conducted histological analyses of total cell counts to assess for cell loss, membrane disruption, and Cath B localization. Finally, we investigated somatosensory changes with the whisker nuisance task. Overall, this study demonstrated that Cath B is not a direct driver of membrane disruption, however, administration of CA-074Me alters Cath B localization and reduced hypersensitivity, emphasizing Cath B being an important component in late secondary pathologies.

The topic of modification of magnesium oxychloride cement (MOC) via specific functional additives is very much pronounced in the research of alternative building materials. This study deals with the co-doping of MOC by 1D and 2D carbon nanomaterials in order to improve its mechanical properties while using tannic acid (TA) as a surfactant. Furthermore, the effect of TA on MOC also covers the improvement of water resistance. As a filler, three size fractions of standard quartz sand are used. The proposed types of MOC-based composites show promising results considering their mechanical, macro- and microstructural, chemical, and hygric properties. The use of 1D and 2D nanoadditives and their mixture enables the improvement of the flexural strength and most of all softening coefficient, the durability parameter characterizing the resistance of the prepared materials to water. For samples immersed in water for 24 h, the compressive strength of all modified composites tested was higher than that of the reference composite. Quantitatively, the developed co-doped composite shows mechanical parameters comparable to or even better than those of commonly used Portland cement-based materials, while maintaining high environmental efficiency. This indicates its potential use as an environmentally friendly alternative to Portland cement-based products.

The textile sector is responsible for a number of environmental impacts. Due to the in-creasing quantities of textiles, their share is rising and a trend reversal from a linear to a circular textile chain is needed. This article presents the background, methodological approach and results of a participatory textile development model. In the commercial B2B sector, three textile prototypes were developed together with users and trialled over several months in three application areas. Textile development took into account the requirements of fibre regeneration in the product design and focused on innova-tive chemical recycling solutions. The three sustainably aligned textiles were subject-ed to spectroscopic and textile-technological tests. Screening life cycle assessments an-alysed their environmental profile and compared it with reference textiles that are used as standard. Overall, it is clear that the three textiles can match conventional ref-erence textiles in terms of quality and have considerable environmental benefits com-pared to the reference textiles. The user survey did identify concerns about a high arti-ficial fibre content, although a general rejection of recycled fibres was not observed. The results show that a transformation is possible, but must start with the fibre com-position; recycling, on the other hand, is of minor importance.

Chronic myelomonocytic leukemia (CMML) is a hematological neoplasm characterized by monocytosis, splenomegaly, thrombocytopenia and anemia. Moreover, it is associ-ated with SRSF2 mutations and rarely with CSF3R variants. The presented case is an 84-year-old patient with persistent anemia and monocytosis. Due to the presence of dysmorphic granulocytes, monocyte atypia and myeloid precursors in peripheral blood, the patient was submitted to bone marrow examination. The diagnosis was consistent with CMML type 2. Hemocoagulative test showed an increase of fibrinolysis markers. Next generation targeted sequencing showed TET2 and SRSF2 mutations, along with an unexpected CSF3R germline missense variant, rarely encountered in CMML. The pa-tient started Azacitidine treatment reaching normal hemostatic process values. In con-clusion, we identified a heterozygous germline mutation that, cooperating with TET2 and SRSF2 variants, have been responsible for the hemorrhagic manifestation.